Thank You all for your comments. Few questions: 1. Will this article change your practice and why? 2. What are the problems encountered when you use the data registry for data collection?
NB It is a case-control study (level 3) where there is a control group.
YOU COPIED FROM EACH OTHER THE EVIDENCE LEVEL WITHOUT PUTTING AN EFFORT OR THEN THINKING FOR A MINUTE.
Thanks to Mohamed Abdullah for his thoughtful answer.
Yes I will perform Hb electrophoresis for all donors especially those in areas where sickle cell anemia is common, in black and in patient with positive family history of SCD
The aim is to detect donors with SCT and explain to them that there may be an increase in the risk of proteinuria and there are no large studies assessing the effect of SCT on long term impact on the kidney
What are the problems encountered when you use the data registry for data collection?
Bias may increase due to different population with different characteristics, unknown data
1. Will this article change your practice and why?
The study is a small case series further larger studies needed.It showed the risk are similar to non SCT except for proteinuria
Hemoglobin electrophoresis to look for the cause of anemia cause in any potential donor with high risk for hemoglobinopathies; family history, and AA.
SCD is absolute contraindication.
Donors with SCT if they wish to donate and the work was satisfactory they need to be aware about the risks, hematology opinion is valuable.
2. What are the problems encountered when you use the data registry for data collection?
Data from registries are prone to biases.
-That data already exist and it save valuable time. However, necessary information may be unavailable or misclassified. Often hard to know exactly how data are generated. Limited to use variables in register. Variation in coding between persons and institutions. Coding used in registers may not be detailed
– Lack of confounder information
– Missing data difficult to handle
– Low or unknown data quality
Definitely this article will add and change our practice , for that any evident base study will allow many donors to be involved in donoation process, whoever in past was declined.
under guidance of this article, healthiest SCT donors should not be excluded from donation , as they have similar outcome, including risk of developing HTN, DM, CVD, but higher rate of declining eGFR , and proteinuria .
The problem encountered of using data registery of data collection, is the bias of data , exactly when collected from many centers , usding different way of collected data, responses of participant , and data loss during time-off followup, also lost participants due to death.
We are accepting in our centre SCT donor without any precautions. after this study, The SCT donor should be counselled on the risk of proteinuria post-donation.
the problems encountered when you use the data registry for data collection?
The data isn’t very precise, Missing data might be difficult to manage and a lack of information.
1. Will this article change your practice and why?
No.
As far as our transplant unit is concerned, we do not come across patients with sickle cell disease or a family history.
It is more relevant to parts of India with high prevalence of Sickle cell disease/ SCT, mainly affecting tribal population.
Theoretically, it opens up avenues by expanding the donor pool, especially older SCT donors.
2. What are the problems encountered when you use the data registry for data collection?
Problems encountered with registry data is lack of homogeneity, dataset is not specific for the disease, some elements crucial with respect to the disease might not be captured adequately in the registry dataset. Sometimes there is lack of standardization, due to changes in criteria/ definitions over time.
1-YES
In our area here, we have high incidence of SCD and unfortunately our work up don’t have SCD screening.
We will try to keep it part of our work up.
Counsel our SCT patient about possibility of having proteinuria and will keep him under strict follow up.
2-difficult to collect précised data and difficult to follow up.(missing ).
-Low data quality
I like that short and sweet reply.
Once you have matched what you should be doing (screening for SCT in all the patients based on higher incidence in your patients), it is good to see you implementing the lessons learned even though this is level 3 evidence.
This is an essential clinical skill to adopt lessons from publications (external validity) to clinical practice, the first step in the implementation of principles of evidence-based medicine. Ajay
Likewise.
Level of evidence (level 4 incorrectly mentioned), as in this thread, is an example that we note many of you have copied each other. That is a setback to our plan in helping you to evolve as an independent thinker of transplantation.
Ajay
Some how may change, we usually do not screen patients for SCT, that would be a risk for proteinuria. we still has small number of patients of sickle cell disease, we use to ask for detailed personal and family history, and trivial number of black Africans population in our community, if there is some suspicion we would screen for it. we have no registry for donation and no cadaveric donation.
What are the problems encountered when you use the data registry for data collection? Lacking some informations, wide and different population characteristics
NO, it will not , simply because we do not screen routinely for SCT and who knows may be we have accepted many of them as a donors without knowing that there are SCT. In short this article ,may not be relevant to may practice.
May be problem with accuracy or validity of the data i.e you may have missing information. Possibility of bias
1- yes,this study change my pracice to do Hb electrophoesis for high risk patient .with family history of sickle cell anemia ,ethicinty
2- data register from data collection .problem regarding information .
Yes, it will change in term of explaining to potential kidney donor the possible long-term effect of SCT and proteinuria. However, in my Centre we do genotype electrophoresis as a routine kidney transplant work may be because is West Africa where the SCD is endemic.
Problem with Data Registry data Collection
additional work for data collection
possible influence of confounder
need for internal and external validation of data collection
Yes of course as we should be screening for SCT especially in black peoples and counselling them regarding evidence of proteinuria and decline of eGFR
Size and number of sample and retrospective study gives different results
Also missing data and always not informative
1- yes I might consider donors with sickle cell trait (SCT)
2- a retrospective study particularly if data is old, there will be a lot of bias in data collection.
This study is motivating to expand and perform wider caliber studies to verify this contentious issue. This study per se is inconclusive and dont put weight against the inclusion of SCT persons in donation programs. Henceforth, my practice will not be changed by this 17 case series study.
i believe that the article will change my practice in that it has open my eyes knowing the significance of SCT and how it affects the kidneys. Ad such patients must be screened that is screen for sickle disease by doing Hb electrophoresis.
knowing what the risk factors the donor has will greatly impact on deciding if to accept the donation especially there are risk of CVD and HTN.
Data registry might only give general information and not specific and one would need to proper studies. While data collection will give precise and specific information.
Well, this article will let me re look at SCT potential donor as possible with greater risk of proteinuria and will need special counselling about the risk. If they accepted the increased risk and they do not have other risk factors they may go for donation. But still we should wait for larger studies with longer follow up.
limitations of registry data is that its retrospective, missing data, lack of certainty about some definition used and it was collected for other reasons not to current question or study,
-yes, considering screening for SCD or trait is a nice point with those with risk factors.
-collecting data from data registry has issues regarding accuracy, validity and missing detailed data and data of follow up.
1- I may screen AA donors for SCT, to follow them. And I will accept donor with SCT for donation
2- There maybe bias of data, as there could be differences in different studies in the inclusion and exclusion criteria, and transplant centres may have different guidelines and definitions of some data. I think also it is difficult to get retrospective information from those involved in the studies previously or contact them
Wadia Elhardallo
2 years ago
Please summarise this article in your own words
Ø Study compared 17 kidney donors with SCT to propensity score matched donor controlson mortality, reduced eGFR, proteinuria and kidney failure. The prevalence of SCT inAfrican American (AA) donors was 11 per 1000 compared to 73 per 1000 in non-donorAA.
Ø Donors with SCT were younger; 33 versus 35 years in controls, nine were AA, sixwere White, and two were listed as other or unknown ethnicities.
Ø After a follow-upperiod of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who werealive, developed hypertension or cardiovascular disease were similar.
Ø No donor withSCT developed an eGFR <30 mL/min/1.73 m2 or kidney failure. SCT was, however,associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 – 22.7), P = .01.
Ø Thissmall and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberalacceptance and that these outcomes reported here likely represent a healthy cohort ofdonors with SCT.
What is the level of evidence provided by this article?
Level 3
Mohamed Ghanem
2 years ago
INTRODUCTION :
Only 34% of US transplant hospitals actually examine possible donor candidates for SCT, according to a survey focused on the topic.
More people should be screened because SCT has been linked to incident chronic kidney disease (CKD), a relative risk of ESKD that is at least two times higher than those with a normal haemoglobin in the nondonor population, and a faster decline in estimated glomerular filtration rate (eGFR) with ageing . Results and Discussion: The findings from this small case series reveal that whereas donors with SCT are more likely to develop proteinuria, the risks of lower eGFR, hypertension, and cardiovascular disease are equal in those with and without SCT
SCD, clinically
many people who have nephropathy experience proteinuria, urine concentrating issues, and worsening kidney damage.
In five major observational studies, Naik et al. found that SCT carriers had greater chances of developing albuminuria (31.8%) compared to noncarriers (19.6%), losing more than 3 mL/min/year of eGFR (22.6% vs. 19.0%), and developing acute CKD (20.7% vs. 13.7%).
Masimango et al. hypothesised a synergistic relationship between high-risk SCT and APOL1 genotypes on lowered eGFR, which was defined as 60 mL/min/1.73 m2, this connection was significantly not based on albuminuria.
the relative risk of ESKD in those with SCT and APOL1 high-risk alleles are 2.06 and 2.09, respectively
This initial studies reveals that donors with SCT who were permitted to donate have done well, but further research is required since they may experience proteinuria, which can be an early symptom of kidney disease. Potential kidney donors with SCT, especially older ones, are excludedThe good results seen here, however, could partly be a result of the fact that only the healthiest SCT candidates were permitted to donate
AA donor candidates favour testing for APOL1 gene polymorphisms and may want to be tested for SCT since that would result in a more thorough informed consent procedure, higher quality research in this field, and most significantly, it would allow for a closer examination of the proteinuria signal
Case – control ( Level III )
CARLOS TADEU LEONIDIO
2 years ago
Please summarise this article in your own words
Although it is not well explained, the greater risk of end-stage renal disease (ESKD) among African-Americans (AA) is known, as well as the presence of Sickle Cell Trait (SCT) and the presence of the APOL 1 polymorphism gene. SCT, 30-40% of the hemoglobin content of red blood cells is hemoglobin S (HgbS) and this level is enough to cause complications such as hematuria and impaired ability to concentrate.
Only 34% of US transplant centers screen for SC, despite the fact that these donors are thought to be at higher risk for more rapid decline in Estimated Glomerular Filtration Rate (eGRF) with aging, incident chronic kidney, and relative risk of ESKD two times bigger.
The results of this study suggest that the risks of reduced eGFR, hypertension and cardiovascular disease are similar in those with and without TSS, but donors with TSS are more likely to develop proteinuria. There was no increase in progression to ESRD in patients with TSS.
Thus, it seems that patients with TSS should be better considered as potential donors.
What is the level of evidence provided by this article?
This is a Serie of cases – level 04.
Dalia Ali
2 years ago
INTRODUCTION
African-Americans (AA) have a higher risk of end-stage kidney disease (ESKD) compared to Whites. The reasons for this are not entirely clear. African-Americans with theAPOL1 high-risk gene polymorphism and those with sickle cell trait (SCT) are more likely to develop ESKD.The prevalence of the former in African-Americans is 11–13% and 8– 9% for the latter.
Long-Term Outcomes
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m2 .None of the donors with SCT developed an eGFR<30 mL/min/1.73m2 or ESKD. The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls; univariable relative risk 5.71(95% CI 5.7 – 22.7), P = .01 (Table 3). No quantitative urinary protein was available on these donors, but three had urine dipstick results: one with “trace,” 20.4 years from donation, one with 2+, 11.7 years from donation and one with 3+,34.9 years fromdonation. In total, 11/17 (64.7%) of cases and 37/68 (54.4%) of controls had available serial creatinine measurements allowing construction of eGFR trajectory after donation. Donors with SCT had an overall eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73m2/year in controls; P= .51
Sickle cell disease (SCD) nephropathy is characterized by cortical
hyperperfusion, medullary hypoperfusion, and an overall augmented vasoconstrictive response to systemic and regional stresses. Notably, hyperfiltration is not a feature of SCD. Clinically, SCD nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease in many. In SCT, 30–40% of the red blood cell hemoglobin content is hemoglobin S (HgbS) and this level is sufficient to cause complications such as hematuria and impaired concentrating ability. Renal microangiographic studies show SCT carriers can indeed experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed in SCD.
In a survey of US transplant centers by Mandelbrot et al., 83% of
transplant centers did not have a policy for screening for sickle cell trait or disease.Moreover, 18% of centers would not consider candidates with SCT.5 KDIGO LiveDonor Practice Guidelines recognized the deficiency in this area and identified expanding knowledge about donors with SCT as a future research direction.
It is perhaps constructive to think about candidates with SCT similar to how we think about AA donor candidates with high-risk APOL1 gene polymorphisms. The prevalence of SCT and high-risk APOL1 risk alleles in AA are ≈ 9% and 13% and the relative risk of ESKD in those with SCT and APOL1 high-risk alleles are 2.06 and 2.09, respectively (Table 4). There have been a total of 133 824 live kidney donors in the US between 1987 and 2015 of whom16278 are African-American and 114 AA donors developed ESKD.
This case series is limited by its small size. Other limitations include
the lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT. The eGFR trajectory results should be interpreted with caution due to the small sample size and small number of serial creatinine measurements. Despite the limitation, this finding could be used as preliminary data for future larger prospective studies.
In all, this preliminary data suggests that donors with SCT who
FIGURE 2 eGFR change post kidney donation
were allowed to donate have done well, but may develop proteinuria which can be an early sign of kidney disease and hence more data is needed. Excluding potential kidney donors with SCT, particularly older ones, should be revisited.
Considering the small size of this series more information regarding
the outcomes of these donors can be readily expanded if centers would have the resources to invite AAdonors back for SCT screening and formal assessment of kidney function.
Level 2
Mohammed Sobair
2 years ago
INTRODUCTION
African-Americans (AA) have a higher risk of end-stage kidney disease compared to Whites.
The reasons for this are not entirely clear.
African-Americans with the APOL1 high-risk gene polymorphism and those with sickle cell trait are more likely to develop ESKD.The prevalence of the former in African-Americans is 11–13% and 8– 9% for the latter.
Here the report on the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT. METHODS :
Study Population . the publicly available dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study, which was a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study.
RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of AlabamaBirmingham.
Donations took place between 1963 and 2007. Results:
there were no significant differences between cases and controls .
Cases and controls were highly comparable on lowest postoperative hematocrit, need for ICU admission or blood transfusions, and volume of intraoperative blood loss .
The proportion of donors with SCT undergoing laparoscopic left nephrectomy was similar to that of controls. Longterm outcomes:
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR.
None of the donors with SCT developed an eGFR.
The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls. DISCUSSION :
The results from this small case series suggest the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with SCT and those who don’t have SCD.
, but donors with SCT are more likely to develop proteinuria. Limitation of the study:
Small size study.
lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
The eGFR trajectory results should be interpreted with caution due to the small sample size and small number of serial creatinine measurements.
Level of evidence lol.
Mohammed Sobair
2 years ago
INTRODUCTION
African-Americans (AA) have a higher risk of end-stage kidney disease compared to Whites.
The reasons for this are not entirely clear.
African-Americans with the APOL1 high-risk gene polymorphism and those with sickle cell trait are more likely to develop ESKD.The prevalence of the former in African-Americans is 11–13% and 8– 9% for the latter.
Here the report on the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT. METHODS :
Study Population . the publicly available dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study, which was a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study.
RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of AlabamaBirmingham.
Donations took place between 1963 and 2007. Results:
there were no significant differences between cases and controls .
Cases and controls were highly comparable on lowest postoperative hematocrit, need for ICU admission or blood transfusions, and volume of intraoperative blood loss .
The proportion of donors with SCT undergoing laparoscopic left nephrectomy was similar to that of controls. Longterm outcomes:
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR.
None of the donors with SCT developed an eGFR.
The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls. DISCUSSION :
The results from this small case series suggest the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with SCT and those who don’t have SCD.
, but donors with SCT are more likely to develop proteinuria. Limitation of the study:
Small size study.
lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
The eGFR trajectory results should be interpreted with caution due to the small sample size and small number of serial creatinine measurements.
Level of evidence111.
Mohammed Sobair
2 years ago
INTRODUCTION
African-Americans (AA) have a higher risk of end-stage kidney disease compared to
Whites.
The reasons for this are not entirely clear.
African-Americans with the APOL1 high-risk gene polymorphism and those with sickle
cell trait are more likely to develop ESKD.The prevalence of the former in African-
Americans is 11–13% and 8– 9% for the latter.
Here the report on the immediate and long-term outcomes of a small case series of 17
live kidney donors with SCT compared to propensity score matched donor controls
without SCT.
METHODS :
Study Population . the publicly available dataset from the Renal and Lung Living Donor
Evaluation (RELIVE) Study, which was a National Institute of Allergy and Infectious
Diseases (NIAID) sponsored study.
RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo
Clinic-Rochester, and the University of Alabama Birmingham.
Donations took place between 1963 and 2007.
Results:
there were no significant differences between cases and controls .
Cases and controls were highly comparable on lowest postoperative hematocrit, need for
ICU admission or blood transfusions, and volume of intraoperative blood loss .
The proportion of donors with SCT undergoing laparoscopic left nephrectomy was
similar to that of controls.
Longterm outcomes:
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%)
developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an
eGFR.
None of the donors with SCT developed an eGFR.
The proportion of donor controls reaching these outcomes were similar with the
exception of proteinuria as four (28.6%) SCT donors developed it compared to three
(5%) in controls.
DISCUSSION :
The results from this small case series suggest the risks of reduced eGFR, hypertension,
and cardiovascular disease are similar in those with SCT and those who don’t have
SCD.
, but donors with SCT are more likely to develop proteinuria.
Limitation of the study:
Small size study.
lack of information in the public dataset on how the diagnosis of SCT was ascertained
and how many donors were actually tested for SCT.
The eGFR trajectory results should be interpreted with caution due to the small sample
size and small number of serial creatinine measurements.
What is the level of evidence provided by this article
rindhabibgmail-com
2 years ago
This was a case series of (17)donors with SCD 9 are AA, 6 are white and 2 of unknown ethnicity. The data was taken from RELIVE study which included 8922 live kidney donors between 1963 to 2007. the aim was to estimate immediate and long term outcomes to compared donors with SCD for loss of eGFR, proteinuria, CVD, death post donation after a follow up of 18.2-+ 10 years. they found that donors with SCD and control who were live developed hypertension or cardiovascular disease death were similar to control.
SCD donors were associated with increased risk of proteinuria, decrease eGFR.
level III
It would change, we are in initial stage of our transplantation currently we don’t have such facility to test, we do not come across patient we are doing in a area patient can not afford to do test from other cities.
low data quality.
Abhijit Patil
2 years ago
Introduction:
Most transplant centers do not screen kidney donor candidates for sickle cell trait
(SCT) and many decline candidates with SCT.
Material and methods:
Renal and Lung Living Donor Evaluation (RELIVE) Study: 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama- Birmingham. Donations took place between 1963 and 2007.
The study compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure.
The prevalence of SCT in African American (AA) donors was 11 per 1000 compared to 73 per 1000 in non-donor AA.
After a follow-up period of 18.2±10.5 years, the proportions of donors with SCT and controls who were alive, developed hypertension or cardiovascular disease were similar.
No donor with SCT developed an eGFR <30 mL/min/1.73 m2 or kidney failure.
SCT was associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 – 22.7), P = .01.
Conclusion:
This small and preliminary case series suggest that donors with SCT should perhaps be considered for kidney donation.
Level of evidence:
Level 3 (retrospective Case control study)
Alyaa Ali
2 years ago
African-American are more likely to develop ESRD, sickle cell trait is important risk factor for developing ESRD, the prevelance of sickle cell trait among African-American about 8% to 9% . Screenìng for SCT in AA kidney candidates is uncommonly done despite its association with ESRD.
Sickle cell disease nephropathy is characterized by cortical hyperperfusion , medullary hypoperfusion and overall vasoconstriction
This study compared the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT to propensity score matched donor controls without SCT.
The data was taken from RELIVE study which included 8922 living kidney donors between 1963 and 2007.
There were 17 donors with SCT, 9 are AA , 6 are white and 2 of unknown ethnicity.
There were no significant differences between donors with SCT and their matched controls in age, gender, ethnicity, exact weight , exact eGFR at donation and relationship to the recipient.
After a mean follow-up of 18.2+/-10.5 years , the proportion of donar with SCT and without SCT are similar in death , development of CVD , HTN except for proteinuria which is more common in donors with SCT.
Donors with SCT had an overall eGFR increase of 2.31 ml/ min/1.73 m2/ year compared to 1.24 ml/min/1.73 m2/year
The results showed the risk of reduced eGFR, HTN and cardiovascular disease are similar in those with or without SCT, but donors with SCT are more likely to develop proteinuria.
Level 3
Yes , do screenìng for SCT as donors may develop proteinuria
Filipe prohaska Batista
2 years ago
This is a retrospective cohort study using data from three American centers (Minnesota, Mayo, and Alabama – RELIEVE) with data from 8922 living donors performed between 1963 and 2007. The idea of this study is to determine the impact of sickle cell trait on kidney donation to donors and recipients.
Of the 8922 patients, 8820 were tested and 17 were positive, 9 African American, 6 Caucasian, and two without an established record. Clinical and laboratory findings were compared in a 1:4 ratio control group.
Despite being a small series of cases, probably due to the characteristics of the studied population being predominantly Caucasian, there was no difference in the clinical evolution of patients with sickle cell trait compared to the control group. Sickle cell trait nephropathy usually progresses with proteinuria, concentration defects,
Naik et al, Masimango et al and Olaniran et al show good results in recipients. The presence of APOL1 genes suggests worse outcomes in kidney transplantation.
Proteinuria and the presence of APOL 1 genes are signs to be considered to avoid kidney transplantation in donors with sickle cell trait. In the absence of these situations, the donor can be considered and proceed with a kidney transplant.
amiri elaf
2 years ago
# Please summarise this article in your own words
*African-Americans (AA) have a higher risk of (ESKD) compared to Whites.
*The AA with the APOL1 high-risk gene polymorphism and those with (SCT) are more likely to develop ESKD.
*The prevalence of the former in African-Americans is 11–13% and 8– 9% for the latter.
*While there is a growing advocacy for testing for APOL1 gene polymorphisms in potential AA donor candidates, screening for SCT in AA kidney candidates is not commonly done despite the fact that identical to those with APOL1 high-risk gene polymorphism.
* (KDIGO) Live Donor Practice Guidelines recognized the deficiency of data in this area and identified expanding knowledge about donors with SCT as a future research direction.
# The aim of study:
To estimate the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT.
# METHODS
Study Population
They used the publicly available dataset from the (RELIVE) Study, which was a (NIAID) sponsored study. RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama- Birmingham. Donations took place between 1963 and 2007.
Donors’ medical records were abstracted for baseline demographic information, anthropometric measurements, prior or current diagnosis or treatment for hypertension and hyperlipidemia, laboratory data, family history of HTN, DM, CKD and (CVD). (BP) readings were collected at multiple time points during the evaluation
process and the average of the three lowest readings was used as baseline.
# Exposure and Outcomes:
The exposure of interest is SCT. None of the participating centers accepted donors with sickle cell disease, and it is unclear from the public dataset how many donors were actually screened for SCT or why those with SCT were screened.
# Statistical Analysis
*Baseline characteristics are reported as frequencies and proportions for categorical variables and median and interquartile range (IQR) for continuous ones.
* Differences between donors with and without SCT were compared using Fisher’s exact test for categorical variables and the Wilcoxson rank-sum test for continuous variables.
*Score matching without replacement was conducted with a ratio of one SCT donor: four donor controls without SCT using a caliper of 1 and matching criteria of age, gender, ethnicity, weight, eGFR at donation, related versus unrelated, study center, and year of donation.
*(GLM) was used to determine factors associated with having SCT and the risk ratio of outcomes associated with having SCT.
Difference in mean eGFR change over time in donors with and without SCT was compared using a generalized linear mixed model and depicted by cubic spline plots.
# RESULTS:
*There were 17 donors with SCT: 9 are (AA), six are White, two listed as other or unknown ethnicity.
*Of the 9 AA donors with SCT,8 donated to related AA recipients, 5/6 White donors donated to related White recipients.
* Pre-donation hemoglobin was 13.6 g/dL in donors with SCT compared to 14.0 g/dL in controls.
* After propensity score matching of one donor with SCT: four donors without SCT on age, gender, ethnicity, exact weight, exact eGFR at donation, relationship to the recipient, study center, and donation year; there were no significant differences
between cases and controls.
# Long-Term Outcomes
*After a mean follow-up of 18.2±10.5 years, one donor with SCT died, two developed CVD, five developed HTN, and five reached an eGFR <60 mL/min/1.73 m2.
*None of the donors with SCT developed an eGFR <30 mL/min/1.73m2 or ESKD. *The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four SCT donors developed it compared to three (5%) in controls.
*No quantitative urinary protein was available on these donors, but three had urine dipstick results: one with “trace,” 20.4 years from donation, one with 2+, 11.7 years from donation and one with 3+, 34.9years from donation.
*In total, 11/17 of cases and 37/68 of controls had available serial creatinine measurements allowing construction of eGFR trajectory after donation.
* Donors with SCT had an overall eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73m2/year in controls.
# The limitation:
*Small size.
*Lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
# This small and preliminary case series suggest that donorswith SCT should perhaps be considered
more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort ofdonors with SCT.
# What is the level of evidence provided by this article?
*Level 3, case control/retrospective study
mai shawky
2 years ago
Summary
· The aim of the study to evaluate the outcome of kidney donation in patients with sickle cell traits that is common among African-Amircans
· No increase risk to develop ESRD, CVD, or hypertension compare with donors without SCD trait. · Only risk observed was higher risk of proteinuria.
· Points of weakness:
o small sample size.
o lack of data about the diagnosis of SCT.
· Will this article change your practice and why?
· Test for SCT is available and affordable and should be done in all donors, especially in high endemic areas
· problems encountered when you use the data registry for data collection?
· Not standardized definition or cut of point for diagnosis.
· Missing data
· It depends on the accuracy and honesty during data entry. Level of evidence: III (case control study)
Hussam Juda
2 years ago
· Only 34% of US transplant centers actually screen potential donor candidates for sickle cell trait (SCT)
· There are big differences in the acceptance of SCT donors, between transplant centres
· SCT has been associated with a faster decline in eGFR with aging, incident CKD, and a relative risk of ESKD that is at least twofold higher than those with a normal hemoglobin in the nondonor population
· This study compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure
METHODS Study Population
· Dataset obtained from the RELIVE Study, which included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama Birmingham, were donations took place between 1963 and 2007
· Participation of donors in the RELIVE Study was requested by mail in 2010-2012. If no response was received, an additional mailing and at least two phone calls were made.
· Donors were asked if they developed diabetes, hypertension, kidney disease, CVD, cancer, and other conditions and were also asked to respond to quality-of-life surveys
Exposure and Outcomes
· None of the participating centers accepted donors with sickle cell disease and it was unclear from the public dataset how many donors screened for SCT or why those with SCT were screened
· Definitions:
– Post-donation HTN: self-reported use of antihypertensive medications or BP ≥140/90 mmHg
– Cardiovascular disease: a diagnosis of myocardial infarction, heart failure, stroke, or need for coronary or peripheral arterial interventions.
-Proteinuria: the presence of one or more of the following: urine dipstick protein ≥1+, urine protein/osmolality ratio >0.42, urine random protein >15 mg/dL, or 24- hour protein >300 mg/day
– ESKD: the need for dialysis or being listed for or receiving a kidney transplant
· The CKD-EPI equation was used to estimate GFR
CONCLUSION
· Risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria
· Excluding potential kidney donors with SCT, particularly older ones, should be revisited
· AA donor candidates support testing for APOL1 gene polymorphisms and perhaps should be screened for SCT as that would lead to a more comprehensive informed consent process, higher quality research in this area and importantly the signal for proteinuria can be studied more carefully
LIMITATIONS
· Small size group
· lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT
· SCT was by self-report and the fact that the field for SCT indicated a response by 8820 donors likely represents the impression of study personnel abstracting records who perhaps entered no SCT if it was not positive but in reality it should have been labeled as not available
What is the level of evidence provided by this article? Level III: Evidence obtained from well-designed controlled trials without randomization
Eusha Ansary
2 years ago
Summary:
Prevalence of sickle cell trait is higher in African American than other US population. The risk of ESRD in SCT is higher than those without it and is comparable to those with the high risk gene APOL1.
The publicly available dataset from RELIVE study was used. Donations took place between 1963 and 2007. Donors’ medical records were abstracted for baseline demographic information, anthropometric measurements, prior or current diagnosis or treatment for hypertension and hyperlipidemia, laboratory data, family history of hypertension, diabetes, kidney disease, and cardiovascular disease (CVD).
The exposure of interest is SCT. Propensity score matching without replacement was conducted with a ratio of one SCT donor: four donor controls without SCT using a caliper of 1 and matching criteria of age (in years), gender, ethnicity, weight, eGFR at donation, related versus unrelated, study center, and year of donation.
There were 17 donors with SCT: nine are African-American (AA), six are White, two listed as other or unknown ethnicity. Both groups are similar except that SCT donors has lower fasting glucose 84 versus 92mgldl, P value 0.002.
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m2.
None of the donors with SCT developed an eGFR <30 mL/min/1.73m2 or ESKD.
Level of evidence: 4
Shereen Yousef
2 years ago
-Most transplant centers do not screen kidney donor candidates for sickle cell trait (SCT) and many decline candidates with SCT since it may associate with kidney disease.
-Its not clear why African-Americans (AA) have higher risk of end-stage kidney disease (ESKD) compared to Whites espicially those with the APOL1 high-risk gene polymorphism and those with sickle cell trait (SCT) .
Despite that the incidence of ESKD in both conditions are almost the same But screening for SCT is not common
34% of US transplant centers screen potential donor candidates for SCT.
SCT has been associated with a faster decline in eGFR with aging, CKD and a relative risk of ESKD that is at least two folds higher normal donors.
Sickle cell disease (SCD) nephropathy is characterized by cortical hyperperfusion, medullary hypoperfusion, and an overall augmented vasoconstrictive response to systemic and regional stresses
SCD nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease .
Renal microangiographic studies show SCT carriers can indeed experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed in SCD.
▪︎METHODS
* Study Population
Data were collected from RELIVE study which included 8922 living kidney donors between 1963 and 2007.
None of the participating centers accepted donors with sickle cell disease and it is unclear from the public dataset how many donors were actually screened for SCT or why those with SCT were screened.
Since SCT is most common in African-Americans, we also determined the ethnicity of the recipients in related donors.
For the 17 donors with SCT: nine are AA, six are White, and two listed as other or unknown ethnicity. Of the nine AA donors with SCT, eight donated to related AA recipients, 5 White donors donated to related White recipients
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m2 (Table 3).
None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2 or ESKD.
these results were similar to controls group
proteinuria occurred in four (28.6%) SCT donors compared to three (5%) in controls
P = .01
The results from this small case series suggest the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
▪︎Three large studies have demonstrated a link between SCT and CKD.
-Naik et al. showed that SCT carriers (from five large observational studies) were more likely to develop albuminuria; 31.8% versus 19.6% in noncarriers, were more likely to lose > 3 mL/min/year of eGFR and were also more likely to develop incident CKD, 20.7% versus 13.7%.
– risk of ESKD in 739 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study with SCT was 5.4% versus 2.6% in non-carriers.
this relative risk of ESKD in REGARDS participants with SCT was comparable to ESKD risk in those with APOL1 high-risk genotypes and having both SCT and APOL1 high-risk genotypes was not associated with increased risk beyond that observed with SCT only
LIMITATIONS
-Small sample size
-how the diagnosis of SCT was ascertained is not clear and how many donors were actually tested for SCT.
In CONCLUSTIONS
SCT donors didn’t have major long term effects except increased proteinuria which is an early sign of kidney disease.
Therefore donors with shouldn’t be declined from donation
What is the level of evidence provided by this article?
Level 3
Theepa Mariamutu
2 years ago
African Americans having the APOL1 high-risk gene polymorphism and those with sickle cell trait are more susceptible to develop ESRD. Evaluate for APOL1 gene polymorphisms in potential African American donor candidates is increasing. however, screening for SCT in African American kidney candidates is not done most of the time.
Despite that the relative risk of ESRD in SCT cases is similar o those with APOL1 high-risk gene polymorphism. Transplant centres policy inclusion of SCT cases as donors are subjective. SCT is accompanied with rapid decrease in eGFR with aging, incident CKD and relative risk of ESRD.
Data of living kidney donors in RELIVE study was used within 44 years. There were 17 donors with SCT 9 were African American, six were white, two of unknown ethnicity.
Donors with SCT had a lower fasting blood sugar than those without SCT.
Propensity score matching of one donor with SCT: four donors without SCT was done on age , gender, ethnicity, weight ,eGFR at donation, relationship to the recipient, no significant differences between cases and control were detected.
The study was followed up for 18.2±10.5 years, one donor with SCT died, two developed CVD, five developed hypertension, and five reached an eGFR <60 mL/min/1.73 m2. None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2or ESKD. One with trace proteinuria developed 20.4 years from donation, one with 2+,11.7 years from donation and one with 3+, 34.9 years from donation. Donors with SCT had an eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73 m2/year in controls.
Reduced eGFR, hypertension, and cardiovascular disease risks are similar in those with and without SCT, but donors with SCT are more prone to develop. SCD nephropathy presents with proteinuria, urinary concentrating defects, and progressive kidney disease.
Studies concluded that SCT are more likely to suffer of proteinuria, lower e GFR and CKD risk. Masimango et al. supposed a similar association between SCT and APOL1 high-risk genotypes on reduced eGFR defined as <60 mL/min/1.73 m2. Others noticed higher rate of decline of GFR in cases with SCT compared to non SCT.
ESKD cases that could have been avoided in donors if no SC donors were accepted is 10 and for APOL1 high-risk alleles a total of 14 cases of ESKD would have been avoided.
The limitation of this study is being small, lack of methodology of SCT detection. Screening new-borns for SCT was not applied until 2006. 17 donors with SCT indicated highly selected candidates who did not have any signs of kidney disease. Donors having SCT whom donated were stable, but may have developed proteinuria as an early sign of renal disease. African American donors need testing for APOL1 gene polymorphisms and possibly screening for SCT as well.
Level of evidence is 3
Ahmed Omran
2 years ago
African Americans with sickle cell trait (SCT) are more vulnerable to develop ESKD, and potential donors selected from this population are not routinely screened for SCT.
Available data of the outcome of kidney donors with SCT are not enough..
SCD nephropathy leads to proteinuria ,hematuria, urinary concentrating defects, and progressive kidney disease.
SCT patients may have renal medullary damage with less incidence than that in SCD.
Several studies proved association between SCT and CKD, but outcome of live kidney donation with SCT is unclear.
83% of transplantation centers do not proceed for screening potential donors for SCT and 18% of centers exclude donors with SCT or SCD
The study aims at evaluation of immediate and long-term outcome of kidney donors with SCT compared to propensity score matched donor controls without SCT, it comprised 17 donors with SCT and 68 matched donors without SCT
Data were collected from data set from RELIVE study.
The study showed that donors with SCT and those without have the same risk of HTN, CVD and decreased GFR but donors with SCT were at higher risk of developing proteinuria which may denote early kidney damage.
Further studies are required to evaluate outcome of live kidney donor with SCT
Limitations: Small size of the sample, and lack of data about tests done to diagnose SCT. GFR values should be interpreted cautiously due to the small sample size
Urine specific gravity and urine microscopy data were not available.
Case control study; level 3.
Tahani Ashmaig
2 years ago
Outcomes of kidney donors with sickle cell trait: A preliminary analysis ☆INTRODUCTION: ▪︎Sickle cell trait (SCT) has been associated with a faster decline in eGFR with aging, incident chronic kidney disease (CKD), and a relative risk of ESKD that is at least 2 fold higher than those with a normal hemoglobin in the non donor population. ☆METHODS Study Population ▪︎ Dataset from the RELIVE Study was used, which included 8922 living kidney donors. ▪︎Donors were asked if they developed diabetes, hypertension, kidney disease, CVD, cancer, and other conditions and were also asked to respond to quality-of-life surveys. Exposure and Outcomes ▪︎The exposure of interest is SCT. None of the participating centers accepted donors with sickle cell disease and it is unclear from the public dataset how many donors were actually screened for SCT or why those with SCT were screened. ☆RESULTS General Characteristics ▪︎There were 17 donors with SCT: nine are African-American (AA), six are White, two listed as other or unknown ethnicity. ▪︎Donors with SCT had a lower fasting plasma glucose, but were otherwise similar to those without SCT. ▪︎Pre-donation hemoglobin was low in donors with SCT compared to controls, Long-Term Outcomes ▪︎ After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed HTN , and five (31.3%) reached an eGFR <60 mL/min/1.73 m2. ▪︎ None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2 or ESKD. ▪︎The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls. ▪︎Donors with SCT had an overall eGFR increase compared to controls. ☆DISCUSSION ▪︎The results from this study suggest the risks of reduced eGFR, HTN, and CVD are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria. ▪︎Clinically, SCD nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease in many. ▪︎SCT can develop hematuria and impaired concentrating ability and can experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed in SCD. ☆Limitations: 1. Small size. 2. Lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT. 3. The eGFR results should be interpreted with caution due to the small sample size and small number of serial creatinine measurements. 4. There is a lower prevalence of SCT in RELIVE donors which may reflect that many candidates with SCT were perhaps not allowed to donate and many if not most were not screened. 5. Screening for SCD was adopted in 1975 but was not fully implemented until 1986. 6. Screening newborns for SCT was not adopted until 2006. 7. SCT was by self-report 8. The 17 donors with SCT reflect a highly selected group that may have lacked any signs of any subtle kidney disease. 9. Urine-specific gravity and urine microscopy are not available in the dataset. ☆Strength: The finding could be used as preliminary data for future larger prospective studies.
☆Conclusion: ▪︎Only the healthiestcandidates with SCT were able to donate. ▪︎This study suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported likely represent a healthy cohort of donors with SCT.
Muntasir Mohammed
2 years ago
Please summarise this article in your own words
INTRODUCTION Sickle cell trait (SCT) prevalence is higher in African American AA) than other US population. The risk of ESRD in SCT is higher than those without it and is comparable to those with the high risk gene APOL1. Despite all of that there is no consistency in transplant centres about screening for SCT, accepting or declining their donation. Even in KDIGO guidelines they acknowledged the lack of literature and ask for further research in those with SCT. This is a study of immediate and long term outcomes of live kidney donors with SCT compared to propensity score matched donor controls without SCT. METHODS Study Population
The publicly available dataset from Renal and Lung living Donor Evaluation (RELIVE) study was used. Donations took place between 1963 and 2007. Donors’ medical records were abstracted for baseline demographic information, anthropometric measurements, prior or current diagnosis or treatment for hypertension and hyperlipidemia, laboratory data,
family history of hypertension, diabetes, kidney disease, and cardiovascular disease (CVD).
Exposure and Outcomes
The exposure of interest is SCT. Propensity score matching without replacement was conducted with a ratio of one SCT donor: four donor controls without SCT using a caliper of 1 and matching criteria of age (in years), gender, ethnicity, weight, eGFR at donation, related versus unrelated, study center, and year of donation.
RESULTS
There were 17 donors with SCT: nine are African-American (AA), six are White, two listed as other or unknown ethnicity. Both groups are similar except that SCT donors has lower fasting glucose 84 versus 92mgldl, P value 0.002.
Long term outcomes After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m2. None of the donors with SCT developed an eGFR <30 mL/min/1.73m2 or ESKD. The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls; univariable relative risk 5.71(95% CI 5.7 – 22.7), P = .01. No quantitative urinary protein was available on these donors, but three had urine dipstick results: one with “trace,” 20.4 years from donation, one with 2+, 11.7 years from donation and one with 3+, 34.9years from donation.
DISCUSSION This study showed that donors with SCT have same out come as those without it, except proteinuria. This case series is limited by:
· Its small size
· Lack of information in the public dataset on how the diagnosis of SCT was ascertained.
· How many donors were actually tested for SCT.
What is the level of evidence provided by this article?
Level 111.
Marius Badal
2 years ago
Sickle cell trait has been an important focus in the article since not many transplant centers do not routinely screen for it. Some may screen and others refuse donors with the trait. SCT is found widely but in the US especially African American it was found that out of 1/10000 population has the trait while 73 /1000 found in non-donor.
It was found that in the African American group the risk is much higher for ESRD when compared with other race like whites with no possible explanation. However, it has been investigated that patients with APOL1 and SCT are at a higher risk of having ESRD.
There is not sufficient investigation dealing or giving a detailed explanation to the current situation. KDIGO has not investigate the matter and there has not been any data.
The population that was studied involved 8922 living kidney donors from a period of 1963 to 2007. The data was obtained from the RELIVE study. The study also involved or included CVD, HTN, DM and kidney diseases.
Based on the above study, the following results were obtained.
1) There were 98.8% donors that involved data of SCT donors of which 17 donors with SCT, 9 were African American, 6 were whites and 2 were listed as others or unknown ethnicity,
2) It was found that SCT donors had a lower FBC
3) Now it was also found that 9 SCT donors of which 8 were donated to African American recipients, and 5/6 white donors donated to related white’s recipients.
4) It was found that the Hb was slightly lower in SCT donors than in non-SCT donors.
5) After a follow-up period of about 18.2 years, the donors with SCT and control group who were alive, developed HTN or CVD were similar.
The study had its limitations and strengths, and they are as follows:
Limitation is that the population size was small and lacked data on how to diagnose SCT.
The strength was that it opened a window of opportunity to possible conduct further investigation in the field.
So, in conclusion the study revealed that there was a reduced in GFR, presence on HTN, CVD in individuals with SCT and non-SCT donors were similar. But it was also noticed that SCT donors there was a higher chance of developing proteinuria.
Also, it was found that African American that have the APOL1 gene must be screen
The level of evidence of this study is 3
I would like to put into practice what I have learnt in this article for information to consider when possible, transplantation to be conducted in the future in my center.
Manal Malik
2 years ago
1- Summary of Outcomes of kidney donors with sickle cell trait: A preliminary analysis:Introduction
34% of US transplant centre showed sickle cell trait as potential candidate .
Kidigo live donor practise guidelines recognized the deficiency of data about donor with SCT and should be as a future research direction.
In this study reported and long terms and comes of a small series of 17 line Kidney donors with SCT compared to matched donor controls with that SCT
Method
study population.
RELIVE study : study form which dataset used. Included 8922 living donors from university of Minnesota.
Exposure out come
No centre accepted donor with sickle cell disease.
Unclear have many donors were screen for SCT.
Results
In 8820 there were 17 donors with SCT:
9 are African-American
6 are white .
2 donors unknown ethnicity
Long term out comes
Follow up of 18 . 2+ 10 . 5 years.
One donor with SCT (5-9%) died
Two (11-8%) develop CVD
Five (29.4%) develop HTN fine (31.3%) EGHR < 60mL/mm/1.73m2
Discussion
The results from this small case series suggest the risk of reduced eGPR, HTN and CVD are similar in those with and without SCT, but donor with SCT are more likely to develop proteinemia.
There is single case report by Rehman of 35 Years who donated man who donated to his 22 years old brother who has SCT as well.
Both donor and recipient had excellent Kidney function 4 years later.
This case series is limited by its small size.
Other limitation of this data set on his the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
Despite the limitation, this finding could be used as preliminary data for future larger prospective studies
Till now screening for SCD not fully implemented
In this data suggest that donor with SCT who were allowed to donate have done well but many develop proteinemia which can be an early disease and hance more data is needed .Garden et -d survey AA donors about their attitudes towards ApoL1 testing and donor fear additional testing .
Considering the small size of this sense more information regarding the outcomes of these donors can readily expand if centre would have the resources to invite AA donor back for SCT screening and assessment of Kidney Function
2What is the level of evidence provided by this article?
-level of evidence is level 4
Zahid Nabi
2 years ago
This article might not change our practicing style as we don’t encounter SCT patients in our part of the world.However if we found a known SCT potential donor we will consider him which otherwise would have been rejected.
What are the problems encountered when you use the data registry for data collection? Incomplete information Bias
Database: a collection of information (i.e., data) arranged for ease of search and retrieval of information. Registry: a collection of information or databases whose organizers receive information from multiple sources, maintain the information over time, and control access to the information.
Hamdy Hegazy
2 years ago
Introduction: African Americans are susceptible to ESRD especially in those with APOL1 gene polymorphism (12%) and Sickle cell trait (SCT). Only 1/3 of US transplant centers screen donors for SCT. Hb S represents 30% of HB in those with SCT and is the cause of mild tubular damage. Aim: assess the outcomes in SCT kidney donors. Outcomes include HTN, DM, CKD, ESRD, CVD, cancer and QOL. Methods: The analyzed data was extracted from collected data in RELIVE trial. Data collected from 1963-2007 included 8922, 68 donors without SCT were matched for 17 kidney donors with SCT. Follow up: 18.2 +/- 10.5 years. Results: kidney donors with SCT didn’t have increased risk for ESRD, CVD or HTN compared to non-SCT donors. SCT kidney donors were at higher risk for proteinuria post-donation (28% vs 5% in controls). Limitations: 1- Small number of cases (17 SCT kidney donors). 2- The actual number of donors with SCT. 3- Lack of information about SCT diagnosis.
What is the level of evidence provided by this article?
Level III
l of evidence (LOE) Description
Level I
Evidence from a systematic review or meta-analysis of all relevant RCTs (randomized controlled trial) or evidence-based clinical practice guidelines based on systematic reviews of RCTs or three or more RCTs of good quality that have similar results.
Level II
Evidence obtained from at least one well-designed RCT (e.g. large multi-site RCT). Level III Evidence obtained from well-designed controlled trials without randomization (i.e. quasi-experimental).
Level IV
Evidence from well-designed case-control or cohort studies.
Level V
Evidence from systematic reviews of descriptive and qualitative studies (meta-synthesis).
Level VI
Evidence from a single descriptive or qualitative study.
Level VII
Evidence from the opinion of authorities and/or reports of expert committees.
fakhriya Alalawi
2 years ago
1- Summary:
Method:
Dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study were used, where 17 kidney donors with sickle cell trait (SCT) were gathered and compared to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure.
Results:
After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive, and developed hypertension or cardiovascular disease were similar. None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2 or ESKD.
The proportion of donor controls reaching these outcomes was similar except for proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls; P = .01.
Conclusion:
This is a small case series; however, it suggests that the risks of reduced eGFR, hypertension and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
Healthy candidates with SCT can be allowed for donation, however large sample of patients is required.
2- This is a case series, level 3 evidence.
Wael Jebur
2 years ago
Sickle cell trait CST is common in African American AA, and it was reported to be associated with increased risk of chronic kidney disease. Nevertheless, most of the transplantation centers declined to test for SCT in potential kidney donors.
As a telling truth, CKD and ESKD are common in AA, probably related to APOL1 gene polymorphism, as the incidence of APOL1 is 73 per 100000 and the focus of this study SCT, with incidence of 11 per 100000. Although there is an escalating advocacy to test for APOL1 polymorphism, testing for SCT is still premature to imply. In order to project the outcome and consequences on SCT kidney donors, this case series study was conducted.
17 SCT kidney donors were compared to non SCT kidney donors’ controls.
follow up period is 18+- 10 years.
End points includes
Mortality, reduced GFR, proteinuria, CKD and ESKD. Furthermore, hypertension and cardiovascular mortality were assessed as well.
Results:
The life expectancy, hypertension and cardiovascular mortality were comparable between the two groups. Similarly, CKD with GFR below 30 and ESKD were not reported in the SCT group.
Proteinuria was the mere complication reported in the context of kidney donation by SCT people reported in this study.
.
Sahar elkharraz
2 years ago
This study address the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to matched donor controls without SCT.
Sickle cell triad are more common in African-Americans.
African-Americans, have a higher risk of ESRD compared to Whites. It’s may related to APOL1 high-risk gene polymorphism.
Patients with sickle cell trait (SCT), are more likely to develop ESRD.
survey specific to sickle cell trait screening showed that only 34% of US transplant centers actually screen potential donor candidates for SCT.
US transplant centers vary widely in their practice regarding whether those with SCT can be considered for donation and there have been no publications regarding the outcome of kidney donors who with SCT.
Sickle cell triad has been associated with a faster decline in estimated glomerular filtration rate (eGFR) with aging, incident chronic kidney disease.
In this study none of the participating centers accepted donors with sickle cell disease and it is unclear from the public dataset how many donors were actually screened for SCT or why those with SCT were screened.
Post donation screening of hypertension/ cardiovascular disease/ proteinuria / eGFR by CKD-EPI equations.
The sickle cell triad not included in screening for donation and also excluded any patients with sickle cell triad.
The screening 8922 kidney donor from 1963-2007, 102 there is no available data regarding SCT and 8820 eligible propensity studies, from them about 8803 no SCT and 17 with SCT, 9 of them are Africa-American.
Donor with SCT has low blood sugar in comparison with control.
All donor with SCT undergoing laparoscopic left nephrectomy and it’s similar to control.
Long term outcome for more than 18.5 years// one donor with SCT died, 2 had cardiovascular disease and 5 develop hypertension and low eGFR < 60ml/min. Non of donor reach eGFR less than 30ml/min.
Proportion of donor with SCT or without similar exceptions in presence of proteinuria which develop in 4 donor with SCT and 3 patients of control.
The results of case series studies suggest risk of eGFR , hypertension and cardiovascular disease similar in both groups.
Sickle cell disease nephropathy is characterized by cortical hyperperfusion, medullary hypoperfusion and vasoconstrictive response to systemic and regional stresses. Hyperfiltration is not a feature of SCD. Clinically it’s manifests with proteinuria, urinary concentrating defects, and progressive kidney disease. In SCT, 30–40% of the red blood cell hemoglobin content is hemoglobin S (HgbS) and this level is sufficient to cause complications such as hematuria and impaired urine concentration.
This study is unaware about data addressing the outcomes of live kidney donors with SCT.
The most of centres not screening for SCT and accept donation with SCT.
Limitations of this study is small size and small number and lack of data.
This study focus for further feature prospective studies to assess prevalence of SCT and complications on kidney pre and post donation.
Q2: Level 3
saja Mohammed
2 years ago
Introduction
African Americans (AA) are at more risk of CKD compared to the white population, no clear cause but may be due to more APOL1 gene polymorphisms and a higher rate of Sickle cell traits and SCD in the black race (AA). The majority of kidney transplant centers are not screening their donors for SCT, in the US > 80% of the centers not screening their donors for SCD, or SCT, and in 18% of centers’ policies, they declined donors with SCT carriers. SCT screening is limited to 1/3 of US centers, however, some centers limited such screening for AA background and declined them from donations based on limited evidence for small observational studies that SCT is associated with a higher risk of albuminuria and progression to ESKD. The KDIGO guideline acknowledged the area of deficiency in relation to SCT donation and call for high-quality future research. However, the center for disease control (CDC) they do recommend that SCT individuals for blood, tissues, and organ donation without clear justification. Aim of the study
To determine the short and long-term outcomes of donors with SCT in comparison to well-matched donors with non-SCT. Method
Exposure of responsiveness is SCT, none of the participating centers accept donations from SCD, and no clear data about how many of them they screened. They used a database from a national RELIVE study from different enters including university centers including 8922 livening kidneys donors from 1963-2007 and the data collected from the electronic medical records provided by the participating centers in addition to the donor survey ( from 2010-2012and recipients’ information, all patients clinical characteristics documented and well matched to the control group of donors with non-. They use propensity scores for matching between the two groups for age gender, wt., ethnicity, related vs nonrelated donation, baseline GFR, and years’ post-donation, SCT, and after exclusions, total number included in this study contains only 17 SCT donors and matched to 85 non-SCT donors s a control group the rate of matching was 1-4, they well -matched by baseline characteristics accept the SCT donors have lower blood sugar at baseline compared to non-SCT donors
Out of 17 SCT donors, only 9 are AA, and the majority are related donors
Mean fu 18 +/- 10 years
Outcome upon long follow-up Hypertension is defined based on donor self-report use of hypertension medication, BP > 140/90 The cardiovascular outcome, MI, Heart failure, stroke, or need for coronary or peripheral vascular intervention Proteinuria: defined by one or more of the following urine dipstick proteins ≥1+, urine protein/osmolality ratio >0.42, urine random protein >15 mg/dL, or 24-hour protein >300 mg/day ESKD, defined by the patient’s need for dialysis or listed for kidney transplantation, they used CKD- EPI calculation for e GFR Results
None of the SCT donors reach ESRD, one died, two got CVD, five developed HTN and another 5 had GFR < 60ml/min/1.73m2 similar outcome in the control group of non-SCT donors except for proteinuria which is more in SCT donors Discussion
SCD nephropathy is characterized by medullary concentration defect with increased vasoconstrictive effect upon the stressful condition with ischemic nephropathy and proteinuria and CKD while SCT carriers have around 30-40% of HBs Which might be enough to cause early concertation defect and hematuria which can progress over time to medullary damage and proteinuria overtime previous three large observational studies have been confirming such risk and SCT carries can progress to CKD(2.7.14). Naik et al. showed that SCT carriers (from five large observational studies) were more likely to develop albuminuria; 31.8% versus 19.6% of noncarriers, were more likely to lose > 3 mL/min/year of eGFR (22.6% vs 19.0%). Based on this pilot study and upon long-term follow up we can tell the risk of hypertension, cardiovascular disease and ESKD were similar in SCT donors compared to non-SCT control donors however the SCT donors are more liable to develop proteinuria.
In AA ethnicity with SCT carriers, they have similar risk stratification as donors with high-risk APOL1 gene polymorphism inheritance. prevalence of SCT and high-risk APOL1 risk alleles in AA are ≈ 9% and 13% and the relative risk of ESKD in those with SCT and APOL1 high-risk alleles are 2.06 and 2.09, respectively. Limitation
Small sample size, case series, (however they are a highly selected group of SCT and well-matched with the control group)
missing nation- database for exposure of interest which is the SCT and depends on self-reporting of SCT (selection bias)
most data during FU is based on donor self-reporting or from donor surveys (bias)
Missing data about the urine-specific gravity and urine microscopy
The GFR change over follow-up time should be interpreted with caution due to the small sample size Conclusion
Based on this small case series they found that highly selected SCT donors have overall good cardiovascular and renal outcomes with a small risk of proteinuria. however the pilot study can be used for future larger prospective research, and till now we should be cautious about the SCT in a particular ethnicity including the APOL1 gene, still may consider them as donors provide they older age healthy with no FH of CKD, and reflect this in my practice we do screen all potential donors for SCT and we declined them for donation as the SCD and SCT in Oman quite common due to consanguinity. we need good quality research to improve our knowledge in this particular area
What is the level of evidence provided by this article?
Case series with control group level 3 B without consistently applied reference standards
Last edited 2 years ago by saja Mohammed
Reem Younis
2 years ago
Please summarise this article in your own words
– African-Americans with the APOL1 high-risk gene polymorphism and those with sickle cell trait (SCT) are more likely to develop ESKD.
-SCT associates with a faster decline in estimated glomerular filtration rate (eGFR) with aging, incident chronic kidney disease (CKD), and a relative risk of ESKD that is at least twofold higher than those with a normal hemoglobin in the nondonor population.
-The study used the publicly available dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study, which was a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study. RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama- Birmingham. Donations took place between 1963 and 2007.
-The results from this small case series suggest the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
-Sickle cell disease (SCD) nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease in many.
-In SCT, 30–40% of the red blood cell hemoglobin content is hemoglobin S (HgbS) and this level is sufficient to cause complications such as hematuria and impaired concentrating ability.
-Renal microangiographic studies show SCT carriers can indeed experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed in SCD.13
-The absolute risk of ESKD in those with SCT, however, was only 8.5 per 1000 person years.
– Masimango et al. suggested a synergistic association between SCT and APOL1
high-risk genotypes on reduced eGFR defined as <60 mL/min/1.73m2.
-Outcomes for recipients of deceased donor kidneys from SCT donors has not been reported.
-The prevalence of SCT in African-American donors was 9/822 and 6/7482 white
donors, yielding a prevalence of 11/1000 and 0.8/1000, respectively.
The corresponding rates in the general populations are 73.1/1000 in AA and 3/1000 in Whites.
-In all, this preliminary data suggests that donors with SCT who were allowed to donate have done well, but may develop proteinuria which can be an early sign of kidney disease and hence more data is needed. Excluding potential kidney donors with SCT, particularly older ones, should be revisited. What is the level of evidence provided by this article?
Level 3
Ramy Elshahat
2 years ago
Outcomes of kidney donors with sickle cell trait: A preliminary analysis
Screening for sickle cell is not a routine workup in kidney donor evaluation only 34% of transplantation centers do screening and some centers will reject donors with sickle cell trait just of unclear data regarding risks for CV morbidity and risk for proteinuria and ESRD. It’s well known that SCD is associated with the risk of proteinuria, tubular dysfunction, and ESRD because of hyperperfusion in the cortex and hypoperfusion in the medulla caused by abnormal HB S but for SCT correlation is still unclear. Aim of the study: a case-control study (level of evidence III) evaluating the immediate and long-term outcomes of live kidney donors with sickle cell trait compared to matched donor controls. Methods: +ve sickle cell trait donors from records of the RELIVE study were contacted. post-donation hypertension, CV disease, proteinuria, and GFR were assessed. Results: Nine were African Americans, six were White, and two were listed as other or unknown ethnicities. Patients were followed-up period for 18.2 ± 10.5 years: -both groups showed no difference regarding the development of hypertension or cardiovascular disease.
-No donor with SCT developed an eGFR <30 mL/min or kidney failure.
-SCT was associated with an increased risk of proteinuria. Conclusion: till now there is still suspicion regarding accepting donors with SCT but as regards this small number of a donor who did well regarding eGFR and hypertension but developed proteinuria, it looks safe to accept but More data is needed. Limitation:
Small sample size.
Data was collected by contacting patients with risk of wrong information
Heba Wagdy
2 years ago
African Americans (AA) with SCT are more likely to develop ESKD, however AA potential donors are not routinely screened for SCT despite the associated risk of ESKD.
Available data about the outcome of kidney donors with SCT is not sufficient.
SCD nephropathy manifest with proteinuria, urinary concentrating defects, progressive kidney disease and hematuria.
SCT carriers may develop renal medullary damage but less than that in SCD.
Several studies showed association between SCT and CKD, but the outcome of live kidney donor with SCT is unclear.
83% of transplant centers don’t screen potential donors for SCTand 18% of centers exclude donors with SCT or SCD
This study aims to evaluate immediate and long-term outcome of kidney donors with SCT compared to propensity score matched donor controls without SCT, it included 17 donors with SCT and 68 matched donors without SCT
Data were obtained from dataset from RELIVE study.
The study suggested that donors with SCT and those without have the same risk of HTN, CVD and decreased GFR but donors with SCT were at higher risk of developing proteinuria which may indicate early kidney disease.
The favorable outcome of this study may be due to careful choice of donors with good health to donate.
Further studies are needed to determine the outcome of live kidney donor with SCT
Limitations:
Small sample size
No data available about tests done to diagnose SCT
Results of GFR should be interpreted cautiously due to small sample size
Urine specific gravity and urine microscopy were not available so donors with hematuria or concentrating defects are not determined.
Level 3, (Case control study)
Mohamad Habli
2 years ago
SCT is a silent disease. SCT is more common among African-American population and associated with a higher risk of end-stage kidney disease compared to white. The prevalence of the Apol1 in African-Americans is 11–13% and 8– 9% for the SCT.
Screening for SCT is not a standardized across transplant centers. Only 34% of US transplant centers actually screen potential donor candidates for SCT. BUT is wider screening for SCT should be considered all donors? Few studies showed that patients with SCT have faster decline in estimated glomerular filtration rate with aging, incident chronic kidney disease, and twofold higher risk of ESRD compared to those with a normal hemoglobin in the nondonor population.
The provided study evaluated dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study. Donations took place between 1963 and 2007.
Donors were asked if they developed diabetes, hypertension, kidney disease, CVD, cancer, and other conditions and were also asked to respond to quality-of-life surveys.
RESULTS
Out of 8922 screened for SCT, 17 donors had SCT: nine are African-American, six are White, two listed as other or unknown ethnicity.
Long-Term Outcomes
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR < 60 mL/min/1.73 m2.
None of the donors with SCT developed an eGFR. The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls; univariable relative risk 5.71.
In summary, the results from this small case series suggest that the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
What is the level of evidence provided by this article?
Level of evidence 3
Will this article change your practice and why?
Results of this study would not change screening plan for donors, as SCT is very rare and very small percentage of population is affected and this study showed no higher risk of ESRD, hypertension or CVD with kidney donation. However in areas with high prevalence of SCD, screening should be done, so that unexplained proteinuria in kidney donor with confirmed SCT could be attributed to SCT.
Nahla Allam
2 years ago
Summary:
Introduction:
· Sickle cell disease (SCD) nephropathy is characterized by cortical hyperperfusion, medullary hypoperfusion, and an augmented vasoconstrictive response to systemic and regional stresses. Notably, hyperfiltration is not a feature of SCD. Clinically, SCD nephropathy manifests with proteinuria and urinary concentration.
· In SCT, 30–40% of the red blood cell hemoglobin content is hemoglobin S (HgbS), and this level is sufficient to cause complications such as hematuria and impaired concentration. Renal microangiographic studies show SCT carriers can indeed experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed inSCD
· African-Americans (AA) have a higher risk of end-stage kidney disease (ESKD) than Whites.
· African-Americans with the APOL1 high-risk gene polymorphism and sickle cell trait (SCT) are more likely to develop ESKD screening for SCT in African-American kidney candidatesESKD in those with SCT is almost identical to those with APOL1 high-risk gene polymorphism.
· Kidney Disease Improving Global Outcomes (KDIGO) Live Donor Practice Guidelines recognized the deficiency of data in this area. In addition, they identified expanding knowledge about donors with SCT as a future research direction.
METHODS: Study Population
We used the publicly available dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study, a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study. The exposure of interest is SCT. None of the participating centers accepted donors with sickle cell disease. It needs to be clarified from
the public dataset how many donors screened for SCT or why those with SCT were screened. Since SCT is most common in African-Americans, we also determined the ethnicity of the recipients in related donors
Statistical Analysis
SCT was compared using Fisher’s exact test for categorical variables and the Wilcoxson rank-sum test for continuous variables. In addition, ascertained propensity score matching without replacement with a ratio of one SCT donor: four donor controls without SCT using a caliper of 1 and matching criteria of age (in years), gender, ethnicity, weight, eGFR at donation, related versus unrelated, study center, and year of contribution.
All analyses were performed on Stata version 17.0 (Stata- Corp LLC)
RESULTS:
General Characteristics:
Ø There were 8820/8922 (98.8%) donors who provided field for the presence of SCT
Ø There were 17 donors with SCT: nine are African-American (AA), six are White, and two are listed as other or unknown ethnicity.
Ø Of the nine AA donors with SCT, eight donated to related AA recipients, and 5/6 White donors donated to related White recipients. Pre-donation hemoglobin was 13.6 g/dL (IQR 12.3, 14.9) in donors with SCT compared to 14.0 g/dL (IQ R 13.1, 15.1) in controls, P = .17.
Ø Donors with SCT had a lower fasting plasma glucose; 84 versus 92 mg/dL; P = .002, but were otherwise similar to those without SCT
The results from this small case series suggest that reduced eGFR, hypertension, and cardiovascular disease risks are similar in those with and without SCT. Still, donors with SCT are more likely to develop proteinuria.
Conclusion :
This preliminary data suggests that donors with SCT who were allowed to donate have done well but may develop proteinuria, which can be an early sign of kidney disease, and hence more data is needed. Therefore, excluding potential kidney donors with SCT, particularly older ones, should be revisited.
Study limitation :
This case series is limited by its small size. Other rules include the need for more information in the public dataset on how to ascertain the diagnosis of SCT and how many donors were tested for SCT.
Three large studies have demonstrated a link between SCT and CKD:
Naik et al. showed that SCT carriers (from five large observational studies) :
1- albuminuria; 31.8% , non carriers, 19.6%
2- CKD, 20.7% versus 13.7%.
3-Stroke was 5.4% versus 2.6% in non-carriers.
Masimango et al.:
A synergistic association between SCT and APOL1 high-risk genotypes on reduced eGFR was defined as <60 mL/min/1.73m2.
Olaniran et al. demonstrated that in 9733 subjects with an eGFR >65 mL/min/1.73 m2 at baseline, eGFR declined by 1.27 mL/min/1.73 m2/year in those without SCT, 1.67 mL/min/1.73 m2/year in those with SCT, and 2.5 mL/min/1.73m2/year in the 230 participants with SCD.
Isaac Abiola
2 years ago
SUMMARY
Introduction:
African American are known to be more at risk of CKD particularly from the established effect of mutation APOL1 gene and coupled with the increase prevalence of sickle cell disease and trait then the tendency to come down early with CKD or ESRD among them is more. However, despite this possibility, only 34% of transplant Centre in US screen for SCT in potential donors.
Aim of the Study:
to report the immediate and long-term outcome in living kidney donor with SCT and matched control without SCT
Method:
the data 8820 participants in the RELIVE study were obtained via mail and phone calls
baseline demography information was obtained from their record
donors were asked if they developed hypertension (BP > 140/90mmHg), DM, CVD (MI, stroke, PAD), kidney disease (24-hour urine >300mg/day) or cancer on phone
the exposure of interest is SCT
all analysis were performed on Stata version 17.0
Results:
17 donors with SCT, 9 were AA, 6 white, 2 listed as others
donor with SCT had a significant lower fasting plasma glucose
after a mean follow up of 18.2+- 10.5 years, lone donor with SCT died, two developed CKD, five developed hypertension, and five reached GFR < 60ml/min
the long-term outcome of the control was similar to the above case except in four of them with proteinuria as against five in the case
there was no significant difference in the yearly loss of GFR rate between the donor with SCT and those without SCT
Conclusion:
The study showed that, the risk of reduction in GFR, or development of hypertension or CVD among donor SCT or without SCT is similar with the exception of higher number of donors with SCT having proteinuria.
Limitation
small sample size that could affect the power of the study
no adequate information on the diagnosis of SCT
no information on the actual number of donors tested for SCT
Level of evidence is 3 because the subject has the outcome of interest
Ghalia sawaf
2 years ago
This study highlights the short and long term outcomes of living donors with SCT
Populations
8922 living donors
From 1963 to 2007
Survey was accomplished between 2010- 2012 about incidence of
DM- Hypertension- CKD CVD- cancer
among living donors
Results
17 LD with SCT(9 AA 6wight 2 other ethnicities )
After propensity score matching 4: 1 ( non SCT : SCT)
there were no difference of results between the two groups according to : age – gender- ethnicity BMI- donation year..
Long term outcomes
After a mean follow- up ( 18 years), living donor with SCT had
5.9% death
11.8% CVD
29.4% Hypertension
31.3% reduction of eGFR less than 60
All of above are similar and with no significant importance when compared with control group
However, proteinuria was found in 28.6% among LD with SCT vs 5% in LD without SCT
RR 5.7% 95% CI P=0.1
Clinically, SCD nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease
There are 3 large studies demonstrate the relation between SCT and the incidence of CKD
It is perhaps constructive to think about candidates with SCT similar to how we think about AA donor candidates with high-risk APOL1 gene polymorphisms
Some limitations
small size of donor group
Lack of information about
Screening criteria of SCT
urine-specific gravity and urine microscopy are not available in the dataset
Level of evidence 3( as professor Ahmed explained)
In our practice
We may think about expand living donors pool by accepting donors with SCT
However, for sure, we need other large studies to confirm the validity of these results
Mohamed Mohamed
2 years ago
V. Outcomes of kidney donors with sickle cell trait: A preliminary analysis Please summarise this article in your own words Introduction
The prevalence of sickle cell trait (SCT) in African-Americans is 8–9%; however, screening for SCT is not commonly done.
Screening potential donors for SCT is done in only 34% of US transplant centers; centers vary widely in accepting those with SCT for donation.
Wider screening is needed as SCT is associated with a faster decline in eGFR with aging, incident CKD, & a relative risk of ESRD ( 2 fold higher than those with a normal Hb hemoglobin in non-donors).
KDIGO identified expanding knowledge about donors with SCT as a future research trend. The study The outcomes (short & long-term) of a small case series of LKDs with SCT compared to matched donor controls without SCT. Study population
Dataset from RELIVE Study (8922 LKDs between 1963 & 2007) was used. Exposure & outcomes None of the participating centers accepted donors with SCD; however, it is unclear from the dataset how many donors were screened for SCT or why those with SCT were screened. The ethnicity of the recipients was determined in related donors. Post-donation HTN was defined as use of medications or BP = or more than 140/90 mmHg. CVD was defined as a diagnosis of MI, HF, stroke, or need for coronary or peripheral arterial interventions. Proteinuria was defined by the presence of 1 or more of the following: – urine dipstick protein !1+ or more – urine protein/osmolality ratio >0.42 – urine random protein >15 mg/dL – 24-hour protein >300 mg/day. CKD-EPI equation was used to estimate GFR. ESKD defined by the need for dialysis or being listed for or a kidney transplant. Statistical analysis
Stata version 17.0 (Stata-Corp LLC) was used for analysis. Results General Characteristics
Total number of donors: 8922
Field for the presence of SCT was present in 8820 (98.8%).
The number of donors with SCT: 17 (9 African-American, 6 White, 2 unknown ethnicity).
Donors with SCT had a lower FBG; otherwise similar to those without SCT.
Pre-donation Hb was 13.6 g/dL versus 14.0 g/dL in controls.
Long-Term Outcomes (a mean follow-up of 18.2± 10.5 years):
Deaths: 1(5.9%)
CVD: 2(11.8%)
HTN: 5 (29.4%)
eGFR <60 mL/min: 5 (31.3%)
eGFR <30 mL/min: None
ESKD: None
The proportion of these outcomes were similar between SCT donor & controls.
No urinary protein quantitative in any SCT donor; 3 had urine dipstick (1, trace, 1, 2+, 1, 3+)
Serial creatinine measurements were available in 11/17 (64.7%) of cases & 37/68 (54.4%) of controls.
Donors with SCT had an eGFR increase of 2.13 mL/min/year versus 1.24 mL/min/year in controls. Discussion
Risks of reduced eGFR, HTN, & CVD are similar in SCT & controls.
Donors with SCT are more likely to develop proteinuria.
SCD nephropathy is characterized by cortical
hyper-perfusion, medullary hypo-perfusion, & augmented vasoconstrictive response to systemic & regional stresses.
Hyperfiltration is not a feature of SCD.
Clinical manifests of SCD: proteinuria, urinary concentrating defects, & progressive kidney disease.
In SCT, 30–40% of the RBC hemoglobin content is HgbS ; a level sufficient to cause complications such as hematuria & impaired concentrating ability.
Renal medullary (dt sickling) damage can occur over
time in SCT; but less than in SCD. Studies linking SCT & CKD:
1. Naik et al: SCT carriers were more likely to develop albuminuria (31.8% vs 19.6% in non-carriers) , were more likely to lose > 3 mL/min / year of eGFR (22.6% vs 19.0%) & were also more likely to develop CKD (20.7% versus 13.7%).
2. REGARDS study (739 participants): risk of ESRD with SCT was 5.4% versus 2.6% in non-carriers. The absolute risk of ESRD was only 8.5/1000 person years. Interestingly, this relative
3. Masimango et al.: synergistic association between SCT & APOL1 high-risk genotypes on reduced eGFR (<60 mL/min).
4. Olaniran et al (9733 subjects with baseline eGFR >65 mL/min): eGFR declined by 1.27 mL/min/ year in those without SCT, 1.67 mL/min/year in those with SCT, & 2.5 mL/min/year in the 230 participants with SCD.
5. Rehman et al: a single case report by of a 35-year-old who donated to his 22-year-old brother who has SCT as well; both had excellent kidney function 4 years later.
6. Mandelbrot et al: 83% of transplant centers did not have a policy for screening for SCT or SCD (a survey of US transplant centers); 18% of centers would not consider candidates with SCT.
KDIGO recognized the deficiency in this area and identified expanding knowledge about donors with SCT as a future research direction.
CDC website dedicated to SCD & SCT states that those with SCT can donate blood, tissue & organs. Limitations
The size of case series is small.
Lack of information in dataset on how the diagnosis of SCT was made & how many donors were actually tested for SCT.
The lower prevalence of SCT in RELIVE donors may reflect that many candidates with SCT were perhaps not allowed to donate and many if not most were not screened.
The 17 donors with SCT who donated reflect a high selection of those who have had no any signs of kidney disease such as concentrating defects or hematuria.
Excluding kidney donors with SCT should be reviewed.
More information regarding these outcomes can be expanded if AA donors could be invited back for SCT screening & formal assessment of kidney function. ========================== What is the level of evidence provided by this article? Level V
Mohammad Alshaikh
2 years ago
Please summarise this article in your own words
It is not routine to screen potential donors for sickle cell trait, and many centers would decline these patients from donation, because they are 2 fold increased risk of ESRD. the study reports short and long term out come in 17 living donor candidates extracted from RELIVE study, compared to donor with no SCT.
Primary out come: proteinuria (defined by urine dipstick +1 or more,urineprotein/osmolality ratio >0.42, urine random protein >15 mg/dl or 24 hours protein urine >300 mg/day) , HTN (B/P equal or more than 140/90 mmHg or use of antihypertensive medications), ESRD (need of dialysis or on the waiting list for transplantation), and cardiovascular diesease(MI,heart failure, need for coronary or peripheral intervention, and stroke).
Results: The patients with SCT had lower fasting glucose level (P value =.002) No difference in hemoglobin level, GFR, ICU admission post donation , blood transfusion , volume of intra-operative blood loss in both groups. There were no difference in primary outcome variables but proteinuria was more in the SCT donors (P value= .01).
Limitations:
Small number of patients.
Lack of public data on SCT diagnosis, and how many donors tested for it.
Difficult/ lack of proper data required for better interpretation.
Conclusion: the healthiest donors with SCT are able to donate kidney with favourable outcomes, inspite of higher risk of proteinuria.
African americans should be screened for SCT when they scren for APOL1 gene, and give more comprehensive informed consent, and better evaluation in large study.
What is the level of evidence provided by this article? case control cohort out come study, level IIc
Abdulrahman Ishag
2 years ago
The aim o the study ;
To evaluate the outcome of kidney donor with sickle cell trait
Population;
17 donors with SCT: nine are African-American (AA), six are White, two listed as other or unknown ethnicity.
The method ;
17 kidney donors with SCT were compared to propensity score matched donor controls
on mortality, reduced eGFR, proteinuria and kidney failure.
Statistical analysis;
Baseline characteristics are reported as frequencies and proportions for categorical variables and median and interquartile range (IQR) for continuous ones.
Differences between donors with and without SCT were compared using Fisher’s exact test for categorical variables and the Wilcoxson rank-sum test for continuous variables.
The generalized linear mixed model used eGFR as the dependent variable, SCT as the independent variable and employed a random intercept plus random slope model and an unstructured covariance option. All analyses were performed on Stata version 17.0 (Stata-Corp LLC)
The result;
1-No donor with SCT developed an eGFR <30 mL/min/1.73 m 2 or kidney failure.
2-SCT was, however, associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 – 22.7), P = .01.
The limitation o the study ;
1-small size.
2-The lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
Conclusion;
1-this preliminary data suggests that donors with SCT who were allowed to donate have done well, but may develop proteinuria which can be an early sign of kidney disease and hence more data is needed.
2- This small and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort of donors with SCT
2-Excluding potential kidney donors with SCT, particularly older ones, should be revisited. Nevertheless, the favorable outcomes reported here may also be indicative of the fact that only the health candidates with SCT were able to donate.
3-AA donor candidates support testing for APOL1 gene polymorphisms and perhaps should be screened for SCT as that would lead to a more comprehensive informed consent process, higher quality research in this area and importantly the signal for proteinuria can be studied more carefully.
What is the level of evidence provided by this article?
Level III ( case controlled study )
Hussein Bagha baghahussein@yahoo.com
2 years ago
Introduction
Patients with sickle cell disease (SCD) are disqualified from donating because of a high prevalence of developing CKD. The RR of developing CKD is also slightly higher in patients with SCT as compared to the non-carriers. African Americans have a higher prevalence of SCT due to its evolutionary protective effects against malaria. The prevalence of APOL1 gene polymorphism is 11-13%. The prevalence of SCT is 8-9%. The RR of developing ESRD is similar in both populations but very few centers screen for SCT and there are no guidelines regarding whether to accept these individuals as donors or not. Methodology
This was a case control study that looked at the short and long term outcomes of 17 kidney donors with SCT and compared them to propensity score matched donor controls without SCT. Both the SCT donors and non-SCT donors were selected from the RELIVE study.
The RELIVE study collected data for living kidney donors from 3 centers from 1967 to 2007. The database had 8922 living kidney donors from which 17 donors with SCT and 68 donors without SCT were identified and followed up for an average of 18.2 years.
The exposure of interest was SCT.
The outcome measures were the development of:
Post donation HTN
Cardiovascular disease
Proteinuria
ESKD
Majority of the donors with the SCT were African American (9/16) and 6/16 were Caucasians (6/16). Majority of the SCT donors donated to their relatives. Outcomes
The development of post donation HTN, CVD and CKD (eGFR of < 60 mls/min) was similar between SCT donors and donors without the SCT
However, the development of proteinuria was higher in SCT donors (28.6% compared to donors without SCT (5%)
It is postulated that SCT carriers can experience renal medullary damage over secondary to sickling albeit slower than those with SCD
3 large studies have demonstrated a link between SCT and development of CVD
Naik et al showed that individuals with SCT were more likely to develop albuminuria and CKD (eGFR< 60 mls/min) as compared to the non-carriers. The carriers of SCT were not at an increased risk of developing HTN and CVD which was what was found in this study.
In the REGARDS trial, the risk of developing ESKD was similar in patients with APOL1 gene polymorphism and SCT carriers. However, the risk did not increase if the patients had both APOL1 gene polymorphisms and SCT carrier state.
A study by Masimango et al suggested a synergistic association between SCT and APOL1 high risk gene mutation on reduced eGFR independent of albuminuria.
A study by Olaniran demonstrated a higher decline in GFR in SCT carriers versus non-carriers.
There have been only case reports of outcomes of SCT donors.
This was the first study that looked at SCT donors and compared them to non-SCT donors.
A limitation of this study was the small size and no data available as to how the diagnosis of how the diagnosis of SCT was made
Larger prospective studies are needed to assess the risks of developing CKD, CVD, HTN and proteinuria in SCT donors so that appropriate guidelines are formulated regarding SCT donors
Level of Evidence
This was level III evidence as the it was a case control study with the exposure of interest being SCT and the outcomes were development of CKD, HTN, CVD and proteinuria. The cases were compared to propensity score matched controls
Mohamed Saad
2 years ago
Outcomes of kidney donors with sickle cell trait: A preliminary analysis.
Still this point of long term outcome of kidney donors with SCT has not being cleared and no identifying knowledge about this .
African-American are higher risk to develop ESRD than white people, and also has higher incidence to develop SCT and mainly due to association of APOL 1 gene polymorphism.
It is not routine in many transplant center to screen donors for SCT, in this study try to signify the immediate and long term effect of SCT on mortality, reduced eGFR, proteinuria and kidney failure.
Method:
We compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure.
By collecting data from donors by phone contact or e-mail , check mortality rate and HTN defines as as self-reported use of antihypertensive medications or BP ≥140/90 mmHg .
Cardiovascular disease (CVD) was defined as a diagnosis of myocardial infarction, heart failure, stroke, or need for coronary or peripheral arterial intervention.
CKD-EPI to assess kidney function and ESRD defined as needing for RRT or KTX listing.
Proteinuria defined as urine dipstick protein ≥1+, urine protein/osmolality ratio >0.42, urine random protein >15 mg/dL, or 24- hour protein >300 mg/day.
Result:
After propensity score matching of one donor with SCT: four donors without SCT, there were no significant differences between cases and controls.
After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive, developed hypertension or cardiovascular disease were similar except proteinuria was common than in SCT donors.
Strength points:
This study provided preliminary data for future larger prospective studies.
Limitation:
-small size.
-lack of information in the public dataset on how the diagnosis of SCT.
Conclusion:
Study give us preliminary data about out comes of kidney donors with sickle sell trait and they were associated with risk of proteinuria which may be risk of CKD, but still need large prospective studies to clarify this point.
African-American donor candidates support testing for APOL1 gene polymorphisms and should be screened for SCT .
Level of evidence III(case-control study).
Amit Sharma
2 years ago
Please summarise this article in your own words
Screening for sickle cell trait (SCT) is not done in prospective kidney donor sin majority of transplant centres and those with SCT are rejected as donors, considering faster fall in GFR, increased risk of CKD and ESRD development in such patients, especially if of African-American ethnicity.
The study was conducted based on dataset from RELIVE Study, comparing 17 kidney donors with SCT with 4 times matched donors (between 1963 and 2007) with respect to mortality, eGFR reduction, proteinuria, and renal failure.
Out of 17, 9 were of African-American ethnicity.
After a follow up of 18.2 mean years, the risk of hypertension and cardiovascular disease was similar and none of the SCT donors developed eGFR<30 ml/min. Donors with SCT had higher proteinuria (28.6% versus 5%).
The study had limitations like: small size, lack of data regarding testing of SCT, small number of serum creatinine measurements, urine microscopy and specific gravity were not available in data.
The donors with SCT have similar parameters with respect to reduction in GFR, ESRD and mortality. They may develop proteinuria, which may be an early marker of kidney disease. So, donors with SCT can be considered, if other parameters are met for organ donation, especially in older donors.
What is the level of evidence provided by this article?
Level of evidence: Level III – Case-control study
KAMAL ELGORASHI
2 years ago
SCT screened in some center as a routine, while other not, and some center decline donors with SCT from donation.
The prevalence of SCT in African American AA, was 1/1000, compared to 73/1000 in non-donor AA.
Donors with SCT were younger; 33 VS 35 years in controls, as fellow; 9 were AA, 6 were white, and 2 as others.
AA have higher risk factors of ESKD compared to whites, with no obvious scientific explanation, and those with APOL1 as well as SCT are more risky to develop ESKD, despite this risk , SCT screening in USA for kidney donors are not routinely done in all transplant centers.
The evidence is to proceed for donation or not for SCT donors are not yet clearly available, KDIGO , recognise a deficient data in this area. Methods; Study population;
Data used are from RELIVE study, involving 8922 living kidney donors, from 1963 to 2007.
HTN, DM, kidney diseases, and CVD are involved in the study. Statistical analysis;
Donors with SCT and those without SCT differences were studied using Fishers exact test for categorically variables and the Wilson rank-sum test for continuous variables.
The ratio of SCT donor to controls was 1:4, with similar data; age, sex, ethnicity, weight, eGFR at donation, related VS untrlated. Results:
There were 8820/8922, (98.8%) donors involve data of SCT donors, there were 17 donors with SCT; 9 are AA, 6 are whites, 2 listed to other, or unknown ethnicity.
2.SCT donors, had a lower FBG; 84 VS 92; P=.002,
3.Of 9 SCT donors; 8 were donoated to AA recipients, 5/6 white donors donated to related whites recipients.
4.Predonation Hb was13.6 g/dl in SCT donors compared to 14 gm/dl in non-SCT donors .
5.There were no differences between between cases and controls, according to the propencity score matching of 1 SCTDx/SCTnon-Dx.
6.Cases and controls were highly comparable on lowest postoperative hemotocrit, need ICU admission or BT, and volume of intraoperative blood loss.
7.The proportion of SCT Dx undergoing laparoscopic left nephrectomy was similar to that of controls. Long term outcome:
Mean follow-up is 18.2+/-10.5 years.
One SCT donor died , tow develop CVD, five develop HTN, and five reached an eFGR <60 ml/min/1.73m2.
None of SCT donors develop an eGFR < 30 ml/min/1.72m2, or ESKD.
Similar above mentioned outcome , develop between SCT donors/non-SCT donors, except for proteinuria, which was 4 SCT donors/3 in controls
SCT donors had an overall eGFR increase of 2.13 ml/min/1.73m2, compared to 1.24 ml/min/1.73m2/year in controls; P=.51.
Discussion:
The risk of reduced eGFR, HTN,CVD, in those with SCT and non-SCT donors are similar, but SCT donors are more likely to develop proteinuria.
Sickle cell disease nephropathy is characterized by cortical hyperperfusion, medullary hypoperfusion, and an overall augmented vasoconstrictive response to systemic and regional stresses,(note; hyperfilteration is not a feature of SCD).
SCD manifest by proteinuria, urinary concentrating defects, and progressive kidney disease.
In SCT, 30-40% of red cell Hb, is HgbS, and this level is sufficient to cause complication such as haematuria, and impaired concentrating ability.
Renal microangiographic study show medullary damage over time secondary to sickling , and markedly less than that of SCD.
Studies that link between SCT and CKD;
Naik et al.; showed that SCT carrier are more likely to develop microalbuminuria; 31.8% VS 19.6% in non-carriers were more likely to lose > 3ml/min/year of eGFR,(22.6% VS 19.0%), and also more likely to develop incident CKD 20.7% VS 13.7% , risk of ESKD was 5.4% VS 2.6% in non-carriers.
Olaniran et al.; showed that in 9733 participants with an eGFR >65 ml/min/1.73m2, at base line , show eGFR decline by 1.27 ml/min/year in those without SCT, while decline by 1.67 ml/min /year in those with SCT, and 2.5 ml/min/year in the 230 participants with SCD.
In all , this data suggests that SCT donors who were donate have done well , but may develop proteinuria, which can be early sign of kidney disease.
Excluding potential donors with SCT, particularly older ones . should be revisited, but healthiest one is advisable.
Hi Dr Kamal,
That is a very good summary, that is not difficult to write. I am looking for the strengths and limitations of this publication to be described the way a senior fellow and experienced clinicians would do. Only then would one be able to determine whether to adopt lessons from publications to clinical practice, the first step in the implementation of principles of evidence-based medicine.
Ajay
Hadeel Badawi
2 years ago
Please summarise this article in your own words
Screening for SCT in African-American kidney candidates is not commonly done despite the fact that the relative risk of ESKD in those with SCT is almost identical to those with APOL1 high-risk gene polymorphism. The outcome of kidney donors who harbor the SCT need to evaluated.
Study population:
Participant from (RELIVE) Study, which included 8922 living kidney donors from 3 transplant centers.
Donations took place between 1963 and 2007.and donors were contacted in 2010–2012.
17 live kidney donors with SCT compared to 68 propensity score matched donor controls without SCT. The matching 1:4. Exposure The exposure of interest is SCT.
The participating center excluded donors with sickle cell disease. Outcomes; Post-donation HTN; CVD; Proteinuria and ESKD. Results:
The prevalence of SCT in African American (AA) donors was 11 per 1000 compared to 73 per 1000 in non-donor AA.
Donors with SCT were younger, 9 were AA, 6 were White, and 2 unknown ethnicities.
The follow-up period of 18.2±10.5 years.
The proportions of donors with SCT and controls who were similar for HTN and CVD.
SCT donors have increased risk of proteinuria; RR 5.71
No donor with SCT developed an eGFR <30 mL/min/1.73 m2 or kidney failure.
Donors with SCT had an overall eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73m2/year in controls. Conclusion: The risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria. This small case series suggest that donors with SCT should perhaps be considered more often.
What is the level of evidence provided by this article?
Dear Dr Hadeel, That is a very good summary, that is not difficult to write. I am looking for the strengths and limitations of this publication to be described. Ajay
Abdullah hindawy
2 years ago
Please summarise this article in your own words
This article discuss the outcome of kidney donation in patients with sickle cell traits.
Sct is more prevelance in african amircan
The study found that patient with sct have no increase risk to develop Esrd ,CVD, or hypertension compare with other donors without scd trait but have an increase risk for developing protienurea.
This case control study has multiple limitations:
1_small number of patients with sct.
2_lack of information about the diagnosis of sct.
3_the real number of donors who have or tested for sct.
What is the level of evidence provided by this article?
Level 3 case control study.
Will this article change your practice and why?
Despite the limitations present in this study ,it may changing our criteria to accept patient with sct especially older patient and we live in area where scd is not uncommon (3% of population) and test for sct is available and not cost effective .
What are the problems encountered when you use the data registry for data collection?
multiple problems are present .:
Inconsistent data collection standards
Context of data collection.
Complexity
Changes to defenetions and polices and maintaining data comparability
Lack of some data
The origon data may not accurate or fake .
That is a fantastic analysis of this article, dear Dr Abdulla Hindawy. I am impressed.
Request to you:
Please type abbreviations ‘sct’ in capital letters as SCT, to save me discomfort of reading incorrect syntax.
Weam Elnazer
2 years ago
Methode:
We looked at the data from 9822 LKD that were participants in the RELIVE project ( donation 1963-2007).
Potential donors who had SCD were excluded from the donation process, however, there was a paucity of data about the screening strategy used for SCT.
Post-donation hypertension is defined by the use of anti-hypertensives or a blood pressure reading of more than 140/90. Reduced eGFR, hypertension, and cardiovascular disease risk were all similar in SCT donors and non-SCT donors, although SCT donors had a greater likelihood of developing proteinuria.
Results:
SCT has been associated with a faster decline in estimated glomerular filtration rate (eGFR) with ageing, incident chronic kidney disease (CKD), and a relative risk of ESKD that is at least twofold higher than those with normal haemoglobin in the nondonor population. Perhaps a wider screening should be considered, as this is the case because SCT has been associated with these factors. This is a small case series consisting of 17 live kidney donors that reports on the immediate and long-term effects of SCT in comparison to propensity score matched donor transplants.
Conclusions:
According to the findings of this limited case series, the risks of lower eGFR, hypertension, and cardiovascular disease are comparable in those with and without SCT. On the other hand, donors with SCT are more likely to develop proteinuria, which may be an early symptom of kidney disease.
Reconsidering whether or not to exclude prospective kidney donors with SCT, especially older ones, is something that has to be done.
-Introduction
African-Americans having the APOL1 high-risk gene polymorphism and those with sickle cell trait are more susceptible to develop ESRD.
Testing for APOL1 gene polymorphisms in potential African-American donor candidates is increased , screening for SCT in African-American kidney candidates is not frequently done in spite that the relative risk of ESRD in SCT cases is similar to those with APOL1 high-risk gene polymorphism.
Transplant centers policy regarding including SCT cases as donors are variable .
SCT is accompanied with rapid decrease in eGFR with aging, incident CKD and relative risk of ESRD.
KDIGO noticed insufficient data in this area . Methods
Data of living kidney donors in RELIVE study was used within 44 years .
There were 17 donors with SCT 9 were African-American (AA), six were white, two of unknown ethnicity. Donors with SCT had a lower Fasting blood sugar than those without SCT.
Propensity score matching of one donor with SCT: four donors without SCT was done on age , gender, ethnicity, weight ,eGFR at donation, relationship to the recipient, no significant differences between cases and control were detected. Long term outcomes
Follow-uping for 18.2±10.5 years, one donor with SCT
died, two developed CVD, five developed hypertension, and five reached an eGFR <60 mL/min/1.73 m2 .
None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2or ESKD.
One with trace proteinuria developed 20.4 years from donation, one with 2+,11.7 years from donation and one with 3+, 34.9 years from donation.
Donors with SCT had an eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73 m2/year in controls. Discussion
Reduced eGFR, hypertension, and cardiovascular disease risks are similar in those with and without SCT, but donors with SCT are more prone to develop
Proteinuria.
SCD nephropathy presents with proteinuria, urinary concentrating defects, and progressive kidney disease .
SCT carriers can suffer renal medullary affection due to sickling more than SCD cases.
Studies concluded that SCT are more likely to suffer of proteinuria , lower e GFR and CKD risk.
Masimango et al. supposed a similar association between SCT and APOL1 high-risk genotypes on reduced eGFR defined as <60 mL/min/1.73 m2.
Others noticed higher rate of decline of GFR in cases with SCT compared to non SCT.
There are sparse data on outcome of donation of SCT case to SCT recipient.
CDC decided that SCT can donate blood ,tissue and organs.
ESKD cases that could have been avoided in AA donors if no SCTdonors were accepted is 10 and for APOL1 high-risk alleles a total of 14 cases of ESKD would have been avoided.
The limitations of this study is being small ,lack of methodology of SCT detection.
Screening newborns for SCT wasnot applied until 2006.
17 donors with SCT indicated highly selected candidates whom did not have any signs of kidney disease.
Donors having SCT whom donated were stable , but may have developed proteinuria as an early sign of renal affection .
AA donors need testing for APOL1 gene polymorphisms and possibly screening for SCT as well.
Outcomes of kidney donors with sickle cell trait: A preliminary analysis
Summary of the Article
This study, reported on immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT. Cases ‘data was retrieved from the Renal and Lung Living Donor Evaluation (RELIVE) Study in the period between 1963 and 2007.
Study Outcome
1. After a median follow up of 18.2+/- 10.5y; 1died(5.9%), two (11.8%) developed CVD, five (29.4%) developed hypertension and five(31.3%) developed an eGFR <60. None of the donors developed an eGFR below 30.
2. The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls.
3. The risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
Limitations of the Study
1. This case series is limited by its small size.
2. No donor had quantitative urinary protein estimate available, only 3 donors had urine dipstick for protein.
3. The lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
What is the level of evidence provided by this article?
INTRODUCTION
-African-Americans (AA) have a higher risk of (ESKD) compared to Whites.
– African-Americans with the APOL1 high-risk gene polymorphism
and those with sickle cell trait (SCT) are more likely to develop ESKD.
The prevalence of the African-Americans is 11–13% and 8– 9% for the latter.3,4 While there is a growing advocacy for testing for APOL1 gene polymorphisms in potential African-American donor can dilates, screening for SCT in African-American kidney candidates is not commonly done despite the fact that the relative risk of ESKD in those with SCT is almost identical to those with APOL1 high-risk gene polymorphism.
-Wider screening perhaps should be considered as SCT has been associated with a faster decline in estimated (eGFR) with aging, incident chronic kidney
– (KDIGO) Live Donor Practice Guidelines recognized the deficiency of data in this area and identified expanding knowledge about donors with SCT as a future research direction. 8 Herein, we report on the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT.
METHODS
-RELIVE Study, which was a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study:
-RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama-Birmingham.
– Donations took place between 1963 and 2007
-Donors were contacted in 2010–2012 by mail requesting participation
in the RELIVE Study.
– Donors were asked if they developed diabetes, hypertension, kidney disease, CVD, cancer, and other conditions and were also asked to respond to quality-of-life surveys
-In all, post donation ascertainment of outcomes came from donor surveys, participating centers’ own records, review of medical records provided by the donors themselves and also from the recipients.
-Proteinuria was defined by the presence of one or more of the following: urine dipstick protein ≥1+, urine protein/osmolality ratio >0.42, urine random protein >15 mg/dL, or 24-
hour protein >300 mg/day.
-Cardiovascular disease (CVD) was defined as a diagnosis of myocardial infarction, heart failure, stroke, or need for coronary or peripheral arterial interventions.
Long-Term Outcomes
-After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m .
-None of the donors with SCT developed an eGFR <30 mL/min/1.73 m 2
or ESKD.
-SCT was, however, associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 – 22.7), P = .01.
-This small and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort of donors with SCT.
Limitation
1-Small size
2- Lack of information on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT. CONCLUSTIONS
-Donors with SCT were doing well with the exception of increased proteinuria which is an early sign of kidney disease.
-Risks of reduced eGFR, HTN, and CV disease were the same and.
-Excluding SCT from donation therefore should be revised particularly in older donors – -AA donors should be screened for SCT as for APOL1 gene for more studies of proteinuria.
What is the level of evidence provided by this article?
Introduction:
Most transplant centers do not screen kidney donor candidates for sickle cell trait, and many decline candidates with sickle cell trait since it may associate with kidney disease.
Aim of the study:
To evaluate the immediate and long-term outcomes of a small case series of 17 live kidney donors with sickle cell trait compared to propensity score matched donor controls without sickle cell trait (SCT).
Methods:
Records from the RELIVE study which included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama Birmingham. Donations took place between 1963 and 2007.
Donors were contacted in 2010–2012 by mail requesting participation in the RELIVE Study.
None of the participating centers accepted donors with sickle cell disease, and it is unclear how many donors were actually screened for SCT or why those with SCT were screened.
Post-donation hypertension, CV disease, proteinuria, and GFR were assessed.
Results:
The prevalence of SCT in African American donors was 11 per 1000 compared to 73 per 1000 in non-donor AA.
Donors with SCT were younger than the controls.
Nine were AA, six were White, and two were listed as other or unknown ethnicities.
After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive and developed hypertension or cardiovascular disease were similar.
No donor with SCT developed an eGFR <30 mL/min or kidney failure.
SCT was associated with an increased risk of proteinuria.
Conclusion:
Patients with SCT who donate their kidneys did well but developed proteinuria, which could be an early sign of renal disease. More data is needed.
Limitation:
Small sample size.
the lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
The eGFR trajectory results should be interpreted with caution due to the small sample size and the small number of serial creatinine measurements.
What is the level of evidence provided by this article?
Please summarise this article in your own words INTRODUCTION
AA are at high risk of ESKD. Those with APOL1 high-risk gene polymorphism (11-13%) and SCT (8-9%) are more likely to develop ESKD. Screening of SCT not done despite identical percentage of APOL1 gene
KEY WORDS: sickle cell trait (SCT), African-Americans (AA)
) AIM OF THE STUDY
Address immediate and long-term outcomes of live donor SCT compared to matched donors without SCT
MATERIALS AND METHODS
They used data from the Renal and Lung Living Donor Evaluation (RELIVE) Study. RELIVE included 8922 living kidney donors (1963 and 2007). Seventeen SCT were matched with 68 donors with no SCT (1:4). Donors were asked if they developed DM, HTN, kidney disease, CVD, cancer, and other conditions and also for quality of life
RESULTS
For the 17 donors with SCT: nine are AA, six are White, and two listed as other or unknown ethnicity. Of the nine AA donors with SCT, eight donated to related AA recipients, 5/6 White donors donated to related White recipients
After a follow-up of 18.2±10.5years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed HTN, and five (31.3%) reached an eGFR<60mL/min. None of the donors with SCT developed an eGFR<30mL/min or ESKD. Outcomes were similar of donor controls with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls
LIMITATIONS
*Small size
*Lack of information on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT
CONCLUSTIONS
Donors with SCT were doing well with the exception of increased proteinuria which is an early sign of kidney disease. Risks of reduced eGFR, HTN, and CV disease were the same and. Excluding SCT from donation therefore should be revised particularly in older donors
AA donors should be screened for SCT as for APOL1 gene for more studies of proteinuria What is the level of evidence provided by this article?
Level 3
Thank You all for your comments. Few questions:
1. Will this article change your practice and why?
2. What are the problems encountered when you use the data registry for data collection?
NB
It is a case-control study (level 3) where there is a control group.
YOU COPIED FROM EACH OTHER THE EVIDENCE LEVEL WITHOUT PUTTING AN EFFORT OR THEN THINKING FOR A MINUTE.
Thanks to Mohamed Abdullah for his thoughtful answer.
Will this article change your practice and why?
What are the problems encountered when you use the data registry for data collection?
Thank You
1. Will this article change your practice and why?
The study is a small case series further larger studies needed.It showed the risk are similar to non SCT except for proteinuria
Hemoglobin electrophoresis to look for the cause of anemia cause in any potential donor with high risk for hemoglobinopathies; family history, and AA.
SCD is absolute contraindication.
Donors with SCT if they wish to donate and the work was satisfactory they need to be aware about the risks, hematology opinion is valuable.
2. What are the problems encountered when you use the data registry for data collection?
Data from registries are prone to biases.
-That data already exist and it save valuable time. However, necessary information may be unavailable or misclassified. Often hard to know exactly how data are generated. Limited to use variables in register. Variation in coding between persons and institutions. Coding used in registers may not be detailed
– Lack of confounder information
– Missing data difficult to handle
– Low or unknown data quality
Thanks Dr Hadeel,
You have highlighted the limitations of secondary data well.
Ajay
Definitely this article will add and change our practice , for that any evident base study will allow many donors to be involved in donoation process, whoever in past was declined.
under guidance of this article, healthiest SCT donors should not be excluded from donation , as they have similar outcome, including risk of developing HTN, DM, CVD, but higher rate of declining eGFR , and proteinuria .
The problem encountered of using data registery of data collection, is the bias of data , exactly when collected from many centers , usding different way of collected data, responses of participant , and data loss during time-off followup, also lost participants due to death.
Thanks Dr Kamal.
You have highlighted the limitations of secondary data well.
Ajay
the problems encountered when you use the data registry for data collection?
1. Will this article change your practice and why?
No.
As far as our transplant unit is concerned, we do not come across patients with sickle cell disease or a family history.
It is more relevant to parts of India with high prevalence of Sickle cell disease/ SCT, mainly affecting tribal population.
Theoretically, it opens up avenues by expanding the donor pool, especially older SCT donors.
2. What are the problems encountered when you use the data registry for data collection?
Problems encountered with registry data is lack of homogeneity, dataset is not specific for the disease, some elements crucial with respect to the disease might not be captured adequately in the registry dataset. Sometimes there is lack of standardization, due to changes in criteria/ definitions over time.
1-YES
In our area here, we have high incidence of SCD and unfortunately our work up don’t have SCD screening.
We will try to keep it part of our work up.
Counsel our SCT patient about possibility of having proteinuria and will keep him under strict follow up.
2-difficult to collect précised data and difficult to follow up.(missing ).
-Low data quality
I like that short and sweet reply.
Once you have matched what you should be doing (screening for SCT in all the patients based on higher incidence in your patients), it is good to see you implementing the lessons learned even though this is level 3 evidence.
This is an essential clinical skill to adopt lessons from publications (external validity) to clinical practice, the first step in the implementation of principles of evidence-based medicine.
Ajay
Likewise.
Level of evidence (level 4 incorrectly mentioned), as in this thread, is an example that we note many of you have copied each other. That is a setback to our plan in helping you to evolve as an independent thinker of transplantation.
Ajay
Will this article change your practice and why?
Some how may change, we usually do not screen patients for SCT, that would be a risk for proteinuria.
we still has small number of patients of sickle cell disease, we use to ask for detailed personal and family history, and trivial number of black Africans population in our community, if there is some suspicion
we would screen for it.
we have no registry for donation and no cadaveric donation.
What are the problems encountered when you use the data registry for data collection?
Lacking some informations, wide and different population characteristics
This article gives us 3 important ideas
What are the problems encountered when you use the data registry for data collection?
Missing some detailed information
1- yes,this study change my pracice to do Hb electrophoesis for high risk patient .with family history of sickle cell anemia ,ethicinty
2- data register from data collection .problem regarding information .
Yes, it will change in term of explaining to potential kidney donor the possible long-term effect of SCT and proteinuria. However, in my Centre we do genotype electrophoresis as a routine kidney transplant work may be because is West Africa where the SCD is endemic.
Problem with Data Registry data Collection
Yes of course as we should be screening for SCT especially in black peoples and counselling them regarding evidence of proteinuria and decline of eGFR
Size and number of sample and retrospective study gives different results
Also missing data and always not informative
1- yes I might consider donors with sickle cell trait (SCT)
2- a retrospective study particularly if data is old, there will be a lot of bias in data collection.
This study is motivating to expand and perform wider caliber studies to verify this contentious issue. This study per se is inconclusive and dont put weight against the inclusion of SCT persons in donation programs. Henceforth, my practice will not be changed by this 17 case series study.
i believe that the article will change my practice in that it has open my eyes knowing the significance of SCT and how it affects the kidneys. Ad such patients must be screened that is screen for sickle disease by doing Hb electrophoresis.
knowing what the risk factors the donor has will greatly impact on deciding if to accept the donation especially there are risk of CVD and HTN.
Data registry might only give general information and not specific and one would need to proper studies. While data collection will give precise and specific information.
Well, this article will let me re look at SCT potential donor as possible with greater risk of proteinuria and will need special counselling about the risk. If they accepted the increased risk and they do not have other risk factors they may go for donation. But still we should wait for larger studies with longer follow up.
limitations of registry data is that its retrospective, missing data, lack of certainty about some definition used and it was collected for other reasons not to current question or study,
-yes, considering screening for SCD or trait is a nice point with those with risk factors.
-collecting data from data registry has issues regarding accuracy, validity and missing detailed data and data of follow up.
1- I may screen AA donors for SCT, to follow them. And I will accept donor with SCT for donation
2- There maybe bias of data, as there could be differences in different studies in the inclusion and exclusion criteria, and transplant centres may have different guidelines and definitions of some data. I think also it is difficult to get retrospective information from those involved in the studies previously or contact them
Ø Study compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure. The prevalence of SCT in African American (AA) donors was 11 per 1000 compared to 73 per 1000 in non-donor AA.
Ø Donors with SCT were younger; 33 versus 35 years in controls, nine were AA, six were White, and two were listed as other or unknown ethnicities.
Ø After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive, developed hypertension or cardiovascular disease were similar.
Ø No donor with SCT developed an eGFR <30 mL/min/1.73 m2 or kidney failure. SCT was, however, associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 – 22.7), P = .01.
Ø This small and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort of donors with SCT.
Level 3
INTRODUCTION :
Only 34% of US transplant hospitals actually examine possible donor candidates for SCT, according to a survey focused on the topic.
More people should be screened because SCT has been linked to incident chronic kidney disease (CKD), a relative risk of ESKD that is at least two times higher than those with a normal haemoglobin in the nondonor population, and a faster decline in estimated glomerular filtration rate (eGFR) with ageing .
Results and Discussion:
The findings from this small case series reveal that whereas donors with SCT are more likely to develop proteinuria, the risks of lower eGFR, hypertension, and cardiovascular disease are equal in those with and without SCT
SCD, clinically
many people who have nephropathy experience proteinuria, urine concentrating issues, and worsening kidney damage.
In five major observational studies, Naik et al. found that SCT carriers had greater chances of developing albuminuria (31.8%) compared to noncarriers (19.6%), losing more than 3 mL/min/year of eGFR (22.6% vs. 19.0%), and developing acute CKD (20.7% vs. 13.7%).
Masimango et al. hypothesised a synergistic relationship between high-risk SCT and APOL1 genotypes on lowered eGFR, which was defined as 60 mL/min/1.73 m2, this connection was significantly not based on albuminuria.
the relative risk of ESKD in those with SCT and APOL1 high-risk alleles are 2.06 and 2.09, respectively
This initial studies reveals that donors with SCT who were permitted to donate have done well, but further research is required since they may experience proteinuria, which can be an early symptom of kidney disease. Potential kidney donors with SCT, especially older ones, are excludedThe good results seen here, however, could partly be a result of the fact that only the healthiest SCT candidates were permitted to donate
AA donor candidates favour testing for APOL1 gene polymorphisms and may want to be tested for SCT since that would result in a more thorough informed consent procedure, higher quality research in this field, and most significantly, it would allow for a closer examination of the proteinuria signal
Case – control ( Level III )
Although it is not well explained, the greater risk of end-stage renal disease (ESKD) among African-Americans (AA) is known, as well as the presence of Sickle Cell Trait (SCT) and the presence of the APOL 1 polymorphism gene. SCT, 30-40% of the hemoglobin content of red blood cells is hemoglobin S (HgbS) and this level is enough to cause complications such as hematuria and impaired ability to concentrate.
Only 34% of US transplant centers screen for SC, despite the fact that these donors are thought to be at higher risk for more rapid decline in Estimated Glomerular Filtration Rate (eGRF) with aging, incident chronic kidney, and relative risk of ESKD two times bigger.
The results of this study suggest that the risks of reduced eGFR, hypertension and cardiovascular disease are similar in those with and without TSS, but donors with TSS are more likely to develop proteinuria. There was no increase in progression to ESRD in patients with TSS.
Thus, it seems that patients with TSS should be better considered as potential donors.
This is a Serie of cases – level 04.
INTRODUCTION
African-Americans (AA) have a higher risk of end-stage kidney disease (ESKD) compared to Whites. The reasons for this are not entirely clear. African-Americans with theAPOL1 high-risk gene polymorphism and those with sickle cell trait (SCT) are more likely to develop ESKD.The prevalence of the former in African-Americans is 11–13% and 8– 9% for the latter.
Long-Term Outcomes
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m2 .None of the donors with SCT developed an eGFR<30 mL/min/1.73m2 or ESKD. The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls; univariable relative risk 5.71(95% CI 5.7 – 22.7), P = .01 (Table 3). No quantitative urinary protein was available on these donors, but three had urine dipstick results: one with “trace,” 20.4 years from donation, one with 2+, 11.7 years from donation and one with 3+,34.9 years fromdonation. In total, 11/17 (64.7%) of cases and 37/68 (54.4%) of controls had available serial creatinine measurements allowing construction of eGFR trajectory after donation. Donors with SCT had an overall eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73m2/year in controls; P= .51
Sickle cell disease (SCD) nephropathy is characterized by cortical
hyperperfusion, medullary hypoperfusion, and an overall augmented vasoconstrictive response to systemic and regional stresses. Notably, hyperfiltration is not a feature of SCD. Clinically, SCD nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease in many. In SCT, 30–40% of the red blood cell hemoglobin content is hemoglobin S (HgbS) and this level is sufficient to cause complications such as hematuria and impaired concentrating ability. Renal microangiographic studies show SCT carriers can indeed experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed in SCD.
In a survey of US transplant centers by Mandelbrot et al., 83% of
transplant centers did not have a policy for screening for sickle cell trait or disease.Moreover, 18% of centers would not consider candidates with SCT.5 KDIGO LiveDonor Practice Guidelines recognized the deficiency in this area and identified expanding knowledge about donors with SCT as a future research direction.
It is perhaps constructive to think about candidates with SCT similar to how we think about AA donor candidates with high-risk APOL1 gene polymorphisms. The prevalence of SCT and high-risk APOL1 risk alleles in AA are ≈ 9% and 13% and the relative risk of ESKD in those with SCT and APOL1 high-risk alleles are 2.06 and 2.09, respectively (Table 4). There have been a total of 133 824 live kidney donors in the US between 1987 and 2015 of whom16278 are African-American and 114 AA donors developed ESKD.
This case series is limited by its small size. Other limitations include
the lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT. The eGFR trajectory results should be interpreted with caution due to the small sample size and small number of serial creatinine measurements. Despite the limitation, this finding could be used as preliminary data for future larger prospective studies.
In all, this preliminary data suggests that donors with SCT who
FIGURE 2 eGFR change post kidney donation
were allowed to donate have done well, but may develop proteinuria which can be an early sign of kidney disease and hence more data is needed. Excluding potential kidney donors with SCT, particularly older ones, should be revisited.
Considering the small size of this series more information regarding
the outcomes of these donors can be readily expanded if centers would have the resources to invite AAdonors back for SCT screening and formal assessment of kidney function.
Level 2
INTRODUCTION
African-Americans (AA) have a higher risk of end-stage kidney disease compared to Whites.
The reasons for this are not entirely clear.
African-Americans with the APOL1 high-risk gene polymorphism and those with sickle cell trait are more likely to develop ESKD.The prevalence of the former in African-Americans is 11–13% and 8– 9% for the latter.
Here the report on the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT.
METHODS :
Study Population . the publicly available dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study, which was a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study.
RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of AlabamaBirmingham.
Donations took place between 1963 and 2007.
Results:
there were no significant differences between cases and controls .
Cases and controls were highly comparable on lowest postoperative hematocrit, need for ICU admission or blood transfusions, and volume of intraoperative blood loss .
The proportion of donors with SCT undergoing laparoscopic left nephrectomy was similar to that of controls.
Longterm outcomes:
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR.
None of the donors with SCT developed an eGFR.
The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls.
DISCUSSION :
The results from this small case series suggest the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with SCT and those who don’t have SCD.
, but donors with SCT are more likely to develop proteinuria.
Limitation of the study:
Small size study.
lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
The eGFR trajectory results should be interpreted with caution due to the small sample size and small number of serial creatinine measurements.
Level of evidence lol.
INTRODUCTION
African-Americans (AA) have a higher risk of end-stage kidney disease compared to Whites.
The reasons for this are not entirely clear.
African-Americans with the APOL1 high-risk gene polymorphism and those with sickle cell trait are more likely to develop ESKD.The prevalence of the former in African-Americans is 11–13% and 8– 9% for the latter.
Here the report on the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT.
METHODS :
Study Population . the publicly available dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study, which was a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study.
RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of AlabamaBirmingham.
Donations took place between 1963 and 2007.
Results:
there were no significant differences between cases and controls .
Cases and controls were highly comparable on lowest postoperative hematocrit, need for ICU admission or blood transfusions, and volume of intraoperative blood loss .
The proportion of donors with SCT undergoing laparoscopic left nephrectomy was similar to that of controls.
Longterm outcomes:
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR.
None of the donors with SCT developed an eGFR.
The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls.
DISCUSSION :
The results from this small case series suggest the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with SCT and those who don’t have SCD.
, but donors with SCT are more likely to develop proteinuria.
Limitation of the study:
Small size study.
lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
The eGFR trajectory results should be interpreted with caution due to the small sample size and small number of serial creatinine measurements.
Level of evidence111.
INTRODUCTION
African-Americans (AA) have a higher risk of end-stage kidney disease compared to
Whites.
The reasons for this are not entirely clear.
African-Americans with the APOL1 high-risk gene polymorphism and those with sickle
cell trait are more likely to develop ESKD.The prevalence of the former in African-
Americans is 11–13% and 8– 9% for the latter.
Here the report on the immediate and long-term outcomes of a small case series of 17
live kidney donors with SCT compared to propensity score matched donor controls
without SCT.
METHODS :
Study Population . the publicly available dataset from the Renal and Lung Living Donor
Evaluation (RELIVE) Study, which was a National Institute of Allergy and Infectious
Diseases (NIAID) sponsored study.
RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo
Clinic-Rochester, and the University of Alabama Birmingham.
Donations took place between 1963 and 2007.
Results:
there were no significant differences between cases and controls .
Cases and controls were highly comparable on lowest postoperative hematocrit, need for
ICU admission or blood transfusions, and volume of intraoperative blood loss .
The proportion of donors with SCT undergoing laparoscopic left nephrectomy was
similar to that of controls.
Longterm outcomes:
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%)
developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an
eGFR.
None of the donors with SCT developed an eGFR.
The proportion of donor controls reaching these outcomes were similar with the
exception of proteinuria as four (28.6%) SCT donors developed it compared to three
(5%) in controls.
DISCUSSION :
The results from this small case series suggest the risks of reduced eGFR, hypertension,
and cardiovascular disease are similar in those with SCT and those who don’t have
SCD.
, but donors with SCT are more likely to develop proteinuria.
Limitation of the study:
Small size study.
lack of information in the public dataset on how the diagnosis of SCT was ascertained
and how many donors were actually tested for SCT.
The eGFR trajectory results should be interpreted with caution due to the small sample
size and small number of serial creatinine measurements.
What is the level of evidence provided by this article
This was a case series of (17)donors with SCD 9 are AA, 6 are white and 2 of unknown ethnicity. The data was taken from RELIVE study which included 8922 live kidney donors between 1963 to 2007. the aim was to estimate immediate and long term outcomes to compared donors with SCD for loss of eGFR, proteinuria, CVD, death post donation after a follow up of 18.2-+ 10 years. they found that donors with SCD and control who were live developed hypertension or cardiovascular disease death were similar to control.
SCD donors were associated with increased risk of proteinuria, decrease eGFR.
level III
It would change, we are in initial stage of our transplantation currently we don’t have such facility to test, we do not come across patient we are doing in a area patient can not afford to do test from other cities.
low data quality.
Introduction:
Most transplant centers do not screen kidney donor candidates for sickle cell trait
(SCT) and many decline candidates with SCT.
Material and methods:
Conclusion:
This small and preliminary case series suggest that donors with SCT should perhaps be considered for kidney donation.
Level of evidence:
Level 3 (retrospective Case control study)
African-American are more likely to develop ESRD, sickle cell trait is important risk factor for developing ESRD, the prevelance of sickle cell trait among African-American about 8% to 9% . Screenìng for SCT in AA kidney candidates is uncommonly done despite its association with ESRD.
Sickle cell disease nephropathy is characterized by cortical hyperperfusion , medullary hypoperfusion and overall vasoconstriction
This study compared the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT to propensity score matched donor controls without SCT.
The data was taken from RELIVE study which included 8922 living kidney donors between 1963 and 2007.
There were 17 donors with SCT, 9 are AA , 6 are white and 2 of unknown ethnicity.
There were no significant differences between donors with SCT and their matched controls in age, gender, ethnicity, exact weight , exact eGFR at donation and relationship to the recipient.
After a mean follow-up of 18.2+/-10.5 years , the proportion of donar with SCT and without SCT are similar in death , development of CVD , HTN except for proteinuria which is more common in donors with SCT.
Donors with SCT had an overall eGFR increase of 2.31 ml/ min/1.73 m2/ year compared to 1.24 ml/min/1.73 m2/year
The results showed the risk of reduced eGFR, HTN and cardiovascular disease are similar in those with or without SCT, but donors with SCT are more likely to develop proteinuria.
Level 3
Yes , do screenìng for SCT as donors may develop proteinuria
This is a retrospective cohort study using data from three American centers (Minnesota, Mayo, and Alabama – RELIEVE) with data from 8922 living donors performed between 1963 and 2007. The idea of this study is to determine the impact of sickle cell trait on kidney donation to donors and recipients.
Of the 8922 patients, 8820 were tested and 17 were positive, 9 African American, 6 Caucasian, and two without an established record. Clinical and laboratory findings were compared in a 1:4 ratio control group.
Despite being a small series of cases, probably due to the characteristics of the studied population being predominantly Caucasian, there was no difference in the clinical evolution of patients with sickle cell trait compared to the control group. Sickle cell trait nephropathy usually progresses with proteinuria, concentration defects,
Naik et al, Masimango et al and Olaniran et al show good results in recipients. The presence of APOL1 genes suggests worse outcomes in kidney transplantation.
Proteinuria and the presence of APOL 1 genes are signs to be considered to avoid kidney transplantation in donors with sickle cell trait. In the absence of these situations, the donor can be considered and proceed with a kidney transplant.
# Please summarise this article in your own words
*African-Americans (AA) have a higher risk of (ESKD) compared to Whites.
*The AA with the APOL1 high-risk gene polymorphism and those with (SCT) are more likely to develop ESKD.
*The prevalence of the former in African-Americans is 11–13% and 8– 9% for the latter.
*While there is a growing advocacy for testing for APOL1 gene polymorphisms in potential AA donor candidates, screening for SCT in AA kidney candidates is not commonly done despite the fact that identical to those with APOL1 high-risk gene polymorphism.
* (KDIGO) Live Donor Practice Guidelines recognized the deficiency of data in this area and identified expanding knowledge about donors with SCT as a future research direction.
# The aim of study:
To estimate the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT.
# METHODS
Study Population
They used the publicly available dataset from the (RELIVE) Study, which was a (NIAID) sponsored study. RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama- Birmingham. Donations took place between 1963 and 2007.
Donors’ medical records were abstracted for baseline demographic information, anthropometric measurements, prior or current diagnosis or treatment for hypertension and hyperlipidemia, laboratory data, family history of HTN, DM, CKD and (CVD). (BP) readings were collected at multiple time points during the evaluation
process and the average of the three lowest readings was used as baseline.
# Exposure and Outcomes:
The exposure of interest is SCT. None of the participating centers accepted donors with sickle cell disease, and it is unclear from the public dataset how many donors were actually screened for SCT or why those with SCT were screened.
# Statistical Analysis
*Baseline characteristics are reported as frequencies and proportions for categorical variables and median and interquartile range (IQR) for continuous ones.
* Differences between donors with and without SCT were compared using Fisher’s exact test for categorical variables and the Wilcoxson rank-sum test for continuous variables.
*Score matching without replacement was conducted with a ratio of one SCT donor: four donor controls without SCT using a caliper of 1 and matching criteria of age, gender, ethnicity, weight, eGFR at donation, related versus unrelated, study center, and year of donation.
*(GLM) was used to determine factors associated with having SCT and the risk ratio of outcomes associated with having SCT.
Difference in mean eGFR change over time in donors with and without SCT was compared using a generalized linear mixed model and depicted by cubic spline plots.
# RESULTS:
*There were 17 donors with SCT: 9 are (AA), six are White, two listed as other or unknown ethnicity.
*Of the 9 AA donors with SCT,8 donated to related AA recipients, 5/6 White donors donated to related White recipients.
* Pre-donation hemoglobin was 13.6 g/dL in donors with SCT compared to 14.0 g/dL in controls.
* After propensity score matching of one donor with SCT: four donors without SCT on age, gender, ethnicity, exact weight, exact eGFR at donation, relationship to the recipient, study center, and donation year; there were no significant differences
between cases and controls.
# Long-Term Outcomes
*After a mean follow-up of 18.2±10.5 years, one donor with SCT died, two developed CVD, five developed HTN, and five reached an eGFR <60 mL/min/1.73 m2.
*None of the donors with SCT developed an eGFR <30 mL/min/1.73m2 or ESKD. *The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four SCT donors developed it compared to three (5%) in controls.
*No quantitative urinary protein was available on these donors, but three had urine dipstick results: one with “trace,” 20.4 years from donation, one with 2+, 11.7 years from donation and one with 3+, 34.9years from donation.
*In total, 11/17 of cases and 37/68 of controls had available serial creatinine measurements allowing construction of eGFR trajectory after donation.
* Donors with SCT had an overall eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73m2/year in controls.
# The limitation:
*Small size.
*Lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
# This small and preliminary case series suggest that donorswith SCT should perhaps be considered
more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort ofdonors with SCT.
# What is the level of evidence provided by this article?
*Level 3, case control/retrospective study
Summary
· The aim of the study to evaluate the outcome of kidney donation in patients with sickle cell traits that is common among African-Amircans
· No increase risk to develop ESRD, CVD, or hypertension compare with donors without SCD trait.
· Only risk observed was higher risk of proteinuria.
· Points of weakness:
o small sample size.
o lack of data about the diagnosis of SCT.
· Will this article change your practice and why?
· Test for SCT is available and affordable and should be done in all donors, especially in high endemic areas
· problems encountered when you use the data registry for data collection?
· Not standardized definition or cut of point for diagnosis.
· Missing data
· It depends on the accuracy and honesty during data entry.
Level of evidence: III (case control study)
· Only 34% of US transplant centers actually screen potential donor candidates for sickle cell trait (SCT)
· There are big differences in the acceptance of SCT donors, between transplant centres
· SCT has been associated with a faster decline in eGFR with aging, incident CKD, and a relative risk of ESKD that is at least twofold higher than those with a normal hemoglobin in the nondonor population
· This study compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure
METHODS
Study Population
· Dataset obtained from the RELIVE Study, which included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama Birmingham, were donations took place between 1963 and 2007
· Participation of donors in the RELIVE Study was requested by mail in 2010-2012. If no response was received, an additional mailing and at least two phone calls were made.
· Donors were asked if they developed diabetes, hypertension, kidney disease, CVD, cancer, and other conditions and were also asked to respond to quality-of-life surveys
Exposure and Outcomes
· None of the participating centers accepted donors with sickle cell disease and it was unclear from the public dataset how many donors screened for SCT or why those with SCT were screened
· Definitions:
– Post-donation HTN: self-reported use of antihypertensive medications or BP ≥140/90 mmHg
– Cardiovascular disease: a diagnosis of myocardial infarction, heart failure, stroke, or need for coronary or peripheral arterial interventions.
-Proteinuria: the presence of one or more of the following: urine dipstick protein ≥1+, urine protein/osmolality ratio >0.42, urine random protein >15 mg/dL, or 24- hour protein >300 mg/day
– ESKD: the need for dialysis or being listed for or receiving a kidney transplant
· The CKD-EPI equation was used to estimate GFR
CONCLUSION
· Risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria
· Excluding potential kidney donors with SCT, particularly older ones, should be revisited
· AA donor candidates support testing for APOL1 gene polymorphisms and perhaps should be screened for SCT as that would lead to a more comprehensive informed consent process, higher quality research in this area and importantly the signal for proteinuria can be studied more carefully
LIMITATIONS
· Small size group
· lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT
· SCT was by self-report and the fact that the field for SCT indicated a response by 8820 donors likely represents the impression of study personnel abstracting records who perhaps entered no SCT if it was not positive but in reality it should have been labeled as not available
What is the level of evidence provided by this article?
Level III: Evidence obtained from well-designed controlled trials without randomization
Summary:
Prevalence of sickle cell trait is higher in African American than other US population. The risk of ESRD in SCT is higher than those without it and is comparable to those with the high risk gene APOL1.
The publicly available dataset from RELIVE study was used. Donations took place between 1963 and 2007. Donors’ medical records were abstracted for baseline demographic information, anthropometric measurements, prior or current diagnosis or treatment for hypertension and hyperlipidemia, laboratory data, family history of hypertension, diabetes, kidney disease, and cardiovascular disease (CVD).
The exposure of interest is SCT. Propensity score matching without replacement was conducted with a ratio of one SCT donor: four donor controls without SCT using a caliper of 1 and matching criteria of age (in years), gender, ethnicity, weight, eGFR at donation, related versus unrelated, study center, and year of donation.
There were 17 donors with SCT: nine are African-American (AA), six are White, two listed as other or unknown ethnicity. Both groups are similar except that SCT donors has lower fasting glucose 84 versus 92mgldl, P value 0.002.
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m2.
None of the donors with SCT developed an eGFR <30 mL/min/1.73m2 or ESKD.
Level of evidence: 4
-Most transplant centers do not screen kidney donor candidates for sickle cell trait (SCT) and many decline candidates with SCT since it may associate with kidney disease.
-Its not clear why African-Americans (AA) have higher risk of end-stage kidney disease (ESKD) compared to Whites espicially those with the APOL1 high-risk gene polymorphism and those with sickle cell trait (SCT) .
Despite that the incidence of ESKD in both conditions are almost the same But screening for SCT is not common
34% of US transplant centers screen potential donor candidates for SCT.
SCT has been associated with a faster decline in eGFR with aging, CKD and a relative risk of ESKD that is at least two folds higher normal donors.
Sickle cell disease (SCD) nephropathy is characterized by cortical hyperperfusion, medullary hypoperfusion, and an overall augmented vasoconstrictive response to systemic and regional stresses
SCD nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease .
Renal microangiographic studies show SCT carriers can indeed experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed in SCD.
▪︎METHODS
* Study Population
Data were collected from RELIVE study which included 8922 living kidney donors between 1963 and 2007.
None of the participating centers accepted donors with sickle cell disease and it is unclear from the public dataset how many donors were actually screened for SCT or why those with SCT were screened.
Since SCT is most common in African-Americans, we also determined the ethnicity of the recipients in related donors.
For the 17 donors with SCT: nine are AA, six are White, and two listed as other or unknown ethnicity. Of the nine AA donors with SCT, eight donated to related AA recipients, 5 White donors donated to related White recipients
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m2 (Table 3).
None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2 or ESKD.
these results were similar to controls group
proteinuria occurred in four (28.6%) SCT donors compared to three (5%) in controls
P = .01
The results from this small case series suggest the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
▪︎Three large studies have demonstrated a link between SCT and CKD.
-Naik et al. showed that SCT carriers (from five large observational studies) were more likely to develop albuminuria; 31.8% versus 19.6% in noncarriers, were more likely to lose > 3 mL/min/year of eGFR and were also more likely to develop incident CKD, 20.7% versus 13.7%.
– risk of ESKD in 739 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study with SCT was 5.4% versus 2.6% in non-carriers.
this relative risk of ESKD in REGARDS participants with SCT was comparable to ESKD risk in those with APOL1 high-risk genotypes and having both SCT and APOL1 high-risk genotypes was not associated with increased risk beyond that observed with SCT only
LIMITATIONS
-Small sample size
-how the diagnosis of SCT was ascertained is not clear and how many donors were actually tested for SCT.
In CONCLUSTIONS
SCT donors didn’t have major long term effects except increased proteinuria which is an early sign of kidney disease.
Therefore donors with shouldn’t be declined from donation
What is the level of evidence provided by this article?
Level 3
African Americans having the APOL1 high-risk gene polymorphism and those with sickle cell trait are more susceptible to develop ESRD. Evaluate for APOL1 gene polymorphisms in potential African American donor candidates is increasing. however, screening for SCT in African American kidney candidates is not done most of the time.
Despite that the relative risk of ESRD in SCT cases is similar o those with APOL1 high-risk gene polymorphism. Transplant centres policy inclusion of SCT cases as donors are subjective. SCT is accompanied with rapid decrease in eGFR with aging, incident CKD and relative risk of ESRD.
Data of living kidney donors in RELIVE study was used within 44 years. There were 17 donors with SCT 9 were African American, six were white, two of unknown ethnicity.
Donors with SCT had a lower fasting blood sugar than those without SCT.
Propensity score matching of one donor with SCT: four donors without SCT was done on age , gender, ethnicity, weight ,eGFR at donation, relationship to the recipient, no significant differences between cases and control were detected.
The study was followed up for 18.2±10.5 years, one donor with SCT died, two developed CVD, five developed hypertension, and five reached an eGFR <60 mL/min/1.73 m2. None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2or ESKD. One with trace proteinuria developed 20.4 years from donation, one with 2+,11.7 years from donation and one with 3+, 34.9 years from donation. Donors with SCT had an eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73 m2/year in controls.
Reduced eGFR, hypertension, and cardiovascular disease risks are similar in those with and without SCT, but donors with SCT are more prone to develop. SCD nephropathy presents with proteinuria, urinary concentrating defects, and progressive kidney disease.
Studies concluded that SCT are more likely to suffer of proteinuria, lower e GFR and CKD risk. Masimango et al. supposed a similar association between SCT and APOL1 high-risk genotypes on reduced eGFR defined as <60 mL/min/1.73 m2. Others noticed higher rate of decline of GFR in cases with SCT compared to non SCT.
ESKD cases that could have been avoided in donors if no SC donors were accepted is 10 and for APOL1 high-risk alleles a total of 14 cases of ESKD would have been avoided.
The limitation of this study is being small, lack of methodology of SCT detection. Screening new-borns for SCT was not applied until 2006. 17 donors with SCT indicated highly selected candidates who did not have any signs of kidney disease. Donors having SCT whom donated were stable, but may have developed proteinuria as an early sign of renal disease. African American donors need testing for APOL1 gene polymorphisms and possibly screening for SCT as well.
Level of evidence is 3
African Americans with sickle cell trait (SCT) are more vulnerable to develop ESKD, and potential donors selected from this population are not routinely screened for SCT.
Available data of the outcome of kidney donors with SCT are not enough..
SCD nephropathy leads to proteinuria ,hematuria, urinary concentrating defects, and progressive kidney disease.
SCT patients may have renal medullary damage with less incidence than that in SCD.
Several studies proved association between SCT and CKD, but outcome of live kidney donation with SCT is unclear.
83% of transplantation centers do not proceed for screening potential donors for SCT and 18% of centers exclude donors with SCT or SCD
The study aims at evaluation of immediate and long-term outcome of kidney donors with SCT compared to propensity score matched donor controls without SCT, it comprised 17 donors with SCT and 68 matched donors without SCT
Data were collected from data set from RELIVE study.
The study showed that donors with SCT and those without have the same risk of HTN, CVD and decreased GFR but donors with SCT were at higher risk of developing proteinuria which may denote early kidney damage.
Further studies are required to evaluate outcome of live kidney donor with SCT
Limitations: Small size of the sample, and lack of data about tests done to diagnose SCT. GFR values should be interpreted cautiously due to the small sample size
Urine specific gravity and urine microscopy data were not available.
Case control study; level 3.
Outcomes of kidney donors with sickle cell trait: A preliminary analysis
☆INTRODUCTION:
▪︎Sickle cell trait (SCT) has been associated with a faster decline in eGFR with aging, incident chronic kidney disease (CKD), and a relative risk of ESKD that is at least 2 fold higher than those with a normal hemoglobin in the non donor population.
☆METHODS
Study Population
▪︎ Dataset from the RELIVE Study was used, which included 8922 living kidney donors. ▪︎Donors were asked if they developed diabetes, hypertension, kidney disease, CVD, cancer, and other conditions and were also asked to respond to quality-of-life surveys.
Exposure and Outcomes
▪︎The exposure of interest is SCT. None of the participating centers accepted donors with sickle cell disease and it is unclear from the public dataset how many donors were actually screened for SCT or why those with SCT were screened.
☆RESULTS
General Characteristics
▪︎There were 17 donors with SCT: nine are African-American (AA), six are White, two listed as other or unknown ethnicity.
▪︎Donors with SCT had a lower fasting plasma glucose, but were otherwise similar to those without SCT.
▪︎Pre-donation hemoglobin was low in donors with SCT compared to controls,
Long-Term Outcomes
▪︎ After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed HTN , and five (31.3%) reached an eGFR <60 mL/min/1.73 m2.
▪︎ None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2 or ESKD.
▪︎The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT
donors developed it compared to three (5%) in controls.
▪︎Donors with SCT had an overall eGFR increase compared to controls.
☆DISCUSSION
▪︎The results from this study suggest the risks of reduced eGFR, HTN, and CVD are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
▪︎Clinically, SCD nephropathy manifests with proteinuria, urinary concentrating
defects, and progressive kidney disease in many.
▪︎SCT can develop hematuria and impaired concentrating ability and can experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed in SCD.
☆Limitations:
1. Small size.
2. Lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
3. The eGFR results should be interpreted with caution due to the small sample size and small number of serial creatinine measurements.
4. There is a lower prevalence of SCT in RELIVE donors which may reflect that many candidates with SCT were perhaps not allowed to donate and many if not most were not screened.
5. Screening for SCD was adopted in 1975 but was not fully implemented until 1986.
6. Screening newborns for SCT was not adopted until 2006.
7. SCT was by self-report
8. The 17 donors with SCT reflect a highly selected group that may have lacked any signs of any subtle kidney disease.
9. Urine-specific gravity and urine microscopy are not available in the dataset.
☆Strength: The finding could be used as preliminary data for future larger prospective studies.
☆Conclusion:
▪︎Only the healthiest candidates with SCT were able to donate.
▪︎This study suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported likely represent a healthy cohort of donors with SCT.
INTRODUCTION
Sickle cell trait (SCT) prevalence is higher in African American AA) than other US population. The risk of ESRD in SCT is higher than those without it and is comparable to those with the high risk gene APOL1. Despite all of that there is no consistency in transplant centres about screening for SCT, accepting or declining their donation. Even in KDIGO guidelines they acknowledged the lack of literature and ask for further research in those with SCT. This is a study of immediate and long term outcomes of live kidney donors with SCT compared to propensity score matched donor controls without SCT.
METHODS
Study Population
The publicly available dataset from Renal and Lung living Donor Evaluation (RELIVE) study was used. Donations took place between 1963 and 2007. Donors’ medical records were abstracted for baseline demographic information, anthropometric measurements, prior or current diagnosis or treatment for hypertension and hyperlipidemia, laboratory data,
family history of hypertension, diabetes, kidney disease, and cardiovascular disease (CVD).
Exposure and Outcomes
The exposure of interest is SCT. Propensity score matching without replacement was conducted with a ratio of one SCT donor: four donor controls without SCT using a caliper of 1 and matching criteria of age (in years), gender, ethnicity, weight, eGFR at donation, related versus unrelated, study center, and year of donation.
RESULTS
There were 17 donors with SCT: nine are African-American (AA), six are White, two listed as other or unknown ethnicity. Both groups are similar except that SCT donors has lower fasting glucose 84 versus 92mgldl, P value 0.002.
Long term outcomes
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m2.
None of the donors with SCT developed an eGFR <30 mL/min/1.73m2 or ESKD. The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls; univariable relative risk 5.71(95% CI 5.7 – 22.7), P = .01. No quantitative urinary protein was available on these donors, but three had urine dipstick results: one with “trace,” 20.4 years from donation, one with 2+, 11.7 years from donation and one with 3+, 34.9years from donation.
DISCUSSION
This study showed that donors with SCT have same out come as those without it, except proteinuria. This case series is limited by:
· Its small size
· Lack of information in the public dataset on how the diagnosis of SCT was ascertained.
· How many donors were actually tested for SCT.
Level 111.
Sickle cell trait has been an important focus in the article since not many transplant centers do not routinely screen for it. Some may screen and others refuse donors with the trait. SCT is found widely but in the US especially African American it was found that out of 1/10000 population has the trait while 73 /1000 found in non-donor.
It was found that in the African American group the risk is much higher for ESRD when compared with other race like whites with no possible explanation. However, it has been investigated that patients with APOL1 and SCT are at a higher risk of having ESRD.
There is not sufficient investigation dealing or giving a detailed explanation to the current situation. KDIGO has not investigate the matter and there has not been any data.
The population that was studied involved 8922 living kidney donors from a period of 1963 to 2007. The data was obtained from the RELIVE study. The study also involved or included CVD, HTN, DM and kidney diseases.
Based on the above study, the following results were obtained.
1) There were 98.8% donors that involved data of SCT donors of which 17 donors with SCT, 9 were African American, 6 were whites and 2 were listed as others or unknown ethnicity,
2) It was found that SCT donors had a lower FBC
3) Now it was also found that 9 SCT donors of which 8 were donated to African American recipients, and 5/6 white donors donated to related white’s recipients.
4) It was found that the Hb was slightly lower in SCT donors than in non-SCT donors.
5) After a follow-up period of about 18.2 years, the donors with SCT and control group who were alive, developed HTN or CVD were similar.
The study had its limitations and strengths, and they are as follows:
Limitation is that the population size was small and lacked data on how to diagnose SCT.
The strength was that it opened a window of opportunity to possible conduct further investigation in the field.
So, in conclusion the study revealed that there was a reduced in GFR, presence on HTN, CVD in individuals with SCT and non-SCT donors were similar. But it was also noticed that SCT donors there was a higher chance of developing proteinuria.
Also, it was found that African American that have the APOL1 gene must be screen
The level of evidence of this study is 3
I would like to put into practice what I have learnt in this article for information to consider when possible, transplantation to be conducted in the future in my center.
1- Summary of Outcomes of kidney donors with sickle cell trait: A preliminary analysis:Introduction
34% of US transplant centre showed sickle cell trait as potential candidate .
Kidigo live donor practise guidelines recognized the deficiency of data about donor with SCT and should be as a future research direction.
In this study reported and long terms and comes of a small series of 17 line Kidney donors with SCT compared to matched donor controls with that SCT
Method
study population.
RELIVE study : study form which dataset used. Included 8922 living donors from university of Minnesota.
Exposure out come
No centre accepted donor with sickle cell disease.
Unclear have many donors were screen for SCT.
Results
In 8820 there were 17 donors with SCT:
9 are African-American
6 are white .
2 donors unknown ethnicity
Long term out comes
Follow up of 18 . 2+ 10 . 5 years.
One donor with SCT (5-9%) died
Two (11-8%) develop CVD
Five (29.4%) develop HTN fine (31.3%) EGHR < 60mL/mm/1.73m2
Discussion
The results from this small case series suggest the risk of reduced eGPR, HTN and CVD are similar in those with and without SCT, but donor with SCT are more likely to develop proteinemia.
There is single case report by Rehman of 35 Years who donated man who donated to his 22 years old brother who has SCT as well.
Both donor and recipient had excellent Kidney function 4 years later.
This case series is limited by its small size.
Other limitation of this data set on his the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
Despite the limitation, this finding could be used as preliminary data for future larger prospective studies
Till now screening for SCD not fully implemented
In this data suggest that donor with SCT who were allowed to donate have done well but many develop proteinemia which can be an early disease and hance more data is needed .Garden et -d survey AA donors about their attitudes towards ApoL1 testing and donor fear additional testing .
Considering the small size of this sense more information regarding the outcomes of these donors can readily expand if centre would have the resources to invite AA donor back for SCT screening and assessment of Kidney Function
-level of evidence is level 4
This article might not change our practicing style as we don’t encounter SCT patients in our part of the world.However if we found a known SCT potential donor we will consider him which otherwise would have been rejected.
What are the problems encountered when you use the data registry for data collection?
Incomplete information
Bias
Database: a collection of information (i.e., data) arranged for ease of search and retrieval of information. Registry: a collection of information or databases whose organizers receive information from multiple sources, maintain the information over time, and control access to the information.
Introduction: African Americans are susceptible to ESRD especially in those with APOL1 gene polymorphism (12%) and Sickle cell trait (SCT). Only 1/3 of US transplant centers screen donors for SCT. Hb S represents 30% of HB in those with SCT and is the cause of mild tubular damage.
Aim: assess the outcomes in SCT kidney donors. Outcomes include HTN, DM, CKD, ESRD, CVD, cancer and QOL.
Methods:
The analyzed data was extracted from collected data in RELIVE trial. Data collected from 1963-2007 included 8922, 68 donors without SCT were matched for 17 kidney donors with SCT.
Follow up: 18.2 +/- 10.5 years.
Results: kidney donors with SCT didn’t have increased risk for ESRD, CVD or HTN compared to non-SCT donors.
SCT kidney donors were at higher risk for proteinuria post-donation (28% vs 5% in controls).
Limitations:
1- Small number of cases (17 SCT kidney donors).
2- The actual number of donors with SCT.
3- Lack of information about SCT diagnosis.
Level III
l of evidence (LOE)
Description
Level I
Evidence from a systematic review or meta-analysis of all relevant RCTs (randomized controlled trial) or evidence-based clinical practice guidelines based on systematic reviews of RCTs or three or more RCTs of good quality that have similar results.
Level II
Evidence obtained from at least one well-designed RCT (e.g. large multi-site RCT).
Level III
Evidence obtained from well-designed controlled trials without randomization (i.e. quasi-experimental).
Level IV
Evidence from well-designed case-control or cohort studies.
Level V
Evidence from systematic reviews of descriptive and qualitative studies (meta-synthesis).
Level VI
Evidence from a single descriptive or qualitative study.
Level VII
Evidence from the opinion of authorities and/or reports of expert committees.
1- Summary:
Method:
Dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study were used, where 17 kidney donors with sickle cell trait (SCT) were gathered and compared to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure.
Results:
After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive, and developed hypertension or cardiovascular disease were similar. None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2 or ESKD.
The proportion of donor controls reaching these outcomes was similar except for proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls; P = .01.
Conclusion:
This is a small case series; however, it suggests that the risks of reduced eGFR, hypertension and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
Healthy candidates with SCT can be allowed for donation, however large sample of patients is required.
2- This is a case series, level 3 evidence.
Sickle cell trait CST is common in African American AA, and it was reported to be associated with increased risk of chronic kidney disease. Nevertheless, most of the transplantation centers declined to test for SCT in potential kidney donors.
As a telling truth, CKD and ESKD are common in AA, probably related to APOL1 gene polymorphism, as the incidence of APOL1 is 73 per 100000 and the focus of this study SCT, with incidence of 11 per 100000. Although there is an escalating advocacy to test for APOL1 polymorphism, testing for SCT is still premature to imply. In order to project the outcome and consequences on SCT kidney donors, this case series study was conducted.
17 SCT kidney donors were compared to non SCT kidney donors’ controls.
follow up period is 18+- 10 years.
End points includes
Mortality, reduced GFR, proteinuria, CKD and ESKD. Furthermore, hypertension and cardiovascular mortality were assessed as well.
Results:
The life expectancy, hypertension and cardiovascular mortality were comparable between the two groups. Similarly, CKD with GFR below 30 and ESKD were not reported in the SCT group.
Proteinuria was the mere complication reported in the context of kidney donation by SCT people reported in this study.
.
This study address the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to matched donor controls without SCT.
Sickle cell triad are more common in African-Americans.
African-Americans, have a higher risk of ESRD compared to Whites. It’s may related to APOL1 high-risk gene polymorphism.
Patients with sickle cell trait (SCT), are more likely to develop ESRD.
survey specific to sickle cell trait screening showed that only 34% of US transplant centers actually screen potential donor candidates for SCT.
US transplant centers vary widely in their practice regarding whether those with SCT can be considered for donation and there have been no publications regarding the outcome of kidney donors who with SCT.
Sickle cell triad has been associated with a faster decline in estimated glomerular filtration rate (eGFR) with aging, incident chronic kidney disease.
In this study none of the participating centers accepted donors with sickle cell disease and it is unclear from the public dataset how many donors were actually screened for SCT or why those with SCT were screened.
Post donation screening of hypertension/ cardiovascular disease/ proteinuria / eGFR by CKD-EPI equations.
The sickle cell triad not included in screening for donation and also excluded any patients with sickle cell triad.
The screening 8922 kidney donor from 1963-2007, 102 there is no available data regarding SCT and 8820 eligible propensity studies, from them about 8803 no SCT and 17 with SCT, 9 of them are Africa-American.
Donor with SCT has low blood sugar in comparison with control.
All donor with SCT undergoing laparoscopic left nephrectomy and it’s similar to control.
Long term outcome for more than 18.5 years// one donor with SCT died, 2 had cardiovascular disease and 5 develop hypertension and low eGFR < 60ml/min. Non of donor reach eGFR less than 30ml/min.
Proportion of donor with SCT or without similar exceptions in presence of proteinuria which develop in 4 donor with SCT and 3 patients of control.
The results of case series studies suggest risk of eGFR , hypertension and cardiovascular disease similar in both groups.
Sickle cell disease nephropathy is characterized by cortical hyperperfusion, medullary hypoperfusion and vasoconstrictive response to systemic and regional stresses. Hyperfiltration is not a feature of SCD. Clinically it’s manifests with proteinuria, urinary concentrating defects, and progressive kidney disease. In SCT, 30–40% of the red blood cell hemoglobin content is hemoglobin S (HgbS) and this level is sufficient to cause complications such as hematuria and impaired urine concentration.
This study is unaware about data addressing the outcomes of live kidney donors with SCT.
The most of centres not screening for SCT and accept donation with SCT.
Limitations of this study is small size and small number and lack of data.
This study focus for further feature prospective studies to assess prevalence of SCT and complications on kidney pre and post donation.
Q2: Level 3
Introduction
African Americans (AA) are at more risk of CKD compared to the white population, no clear cause but may be due to more APOL1 gene polymorphisms and a higher rate of Sickle cell traits and SCD in the black race (AA). The majority of kidney transplant centers are not screening their donors for SCT, in the US > 80% of the centers not screening their donors for SCD, or SCT, and in 18% of centers’ policies, they declined donors with SCT carriers. SCT screening is limited to 1/3 of US centers, however, some centers limited such screening for AA background and declined them from donations based on limited evidence for small observational studies that SCT is associated with a higher risk of albuminuria and progression to ESKD. The KDIGO guideline acknowledged the area of deficiency in relation to SCT donation and call for high-quality future research. However, the center for disease control (CDC) they do recommend that SCT individuals for blood, tissues, and organ donation without clear justification.
Aim of the study
To determine the short and long-term outcomes of donors with SCT in comparison to well-matched donors with non-SCT.
Method
Exposure of responsiveness is SCT, none of the participating centers accept donations from SCD, and no clear data about how many of them they screened. They used a database from a national RELIVE study from different enters including university centers including 8922 livening kidneys donors from 1963-2007 and the data collected from the electronic medical records provided by the participating centers in addition to the donor survey ( from 2010-2012and recipients’ information, all patients clinical characteristics documented and well matched to the control group of donors with non-. They use propensity scores for matching between the two groups for age gender, wt., ethnicity, related vs nonrelated donation, baseline GFR, and years’ post-donation, SCT, and after exclusions, total number included in this study contains only 17 SCT donors and matched to 85 non-SCT donors s a control group the rate of matching was 1-4, they well -matched by baseline characteristics accept the SCT donors have lower blood sugar at baseline compared to non-SCT donors
Out of 17 SCT donors, only 9 are AA, and the majority are related donors
Mean fu 18 +/- 10 years
Outcome upon long follow-up
Hypertension is defined based on donor self-report use of hypertension medication, BP > 140/90
The cardiovascular outcome, MI, Heart failure, stroke, or need for coronary or peripheral vascular intervention
Proteinuria: defined by one or more of the following urine dipstick proteins ≥1+, urine protein/osmolality ratio >0.42, urine random protein >15 mg/dL, or 24-hour protein >300 mg/day
ESKD, defined by the patient’s need for dialysis or listed for kidney transplantation, they used CKD- EPI calculation for e GFR
Results
None of the SCT donors reach ESRD, one died, two got CVD, five developed HTN and another 5 had GFR < 60ml/min/1.73m2 similar outcome in the control group of non-SCT donors except for proteinuria which is more in SCT donors
Discussion
SCD nephropathy is characterized by medullary concentration defect with increased vasoconstrictive effect upon the stressful condition with ischemic nephropathy and proteinuria and CKD while SCT carriers have around 30-40% of HBs Which might be enough to cause early concertation defect and hematuria which can progress over time to medullary damage and proteinuria overtime previous three large observational studies have been confirming such risk and SCT carries can progress to CKD(2.7.14). Naik et al. showed that SCT carriers (from five large observational studies) were more likely to develop albuminuria; 31.8% versus 19.6% of noncarriers, were more likely to lose > 3 mL/min/year of eGFR (22.6% vs 19.0%). Based on this pilot study and upon long-term follow up we can tell the risk of hypertension, cardiovascular disease and ESKD were similar in SCT donors compared to non-SCT control donors however the SCT donors are more liable to develop proteinuria.
In AA ethnicity with SCT carriers, they have similar risk stratification as donors with high-risk APOL1 gene polymorphism inheritance. prevalence of SCT and high-risk APOL1 risk alleles in AA are ≈ 9% and 13% and the relative risk of ESKD in those with SCT and APOL1 high-risk alleles are 2.06 and 2.09, respectively.
Limitation
Small sample size, case series, (however they are a highly selected group of SCT and well-matched with the control group)
missing nation- database for exposure of interest which is the SCT and depends on self-reporting of SCT (selection bias)
most data during FU is based on donor self-reporting or from donor surveys (bias)
Missing data about the urine-specific gravity and urine microscopy
The GFR change over follow-up time should be interpreted with caution due to the small sample size
Conclusion
Based on this small case series they found that highly selected SCT donors have overall good cardiovascular and renal outcomes with a small risk of proteinuria. however the pilot study can be used for future larger prospective research, and till now we should be cautious about the SCT in a particular ethnicity including the APOL1 gene, still may consider them as donors provide they older age healthy with no FH of CKD, and reflect this in my practice we do screen all potential donors for SCT and we declined them for donation as the SCD and SCT in Oman quite common due to consanguinity. we need good quality research to improve our knowledge in this particular area
What is the level of evidence provided by this article?
Case series with control group level 3 B without consistently applied reference standards
Please summarise this article in your own words
– African-Americans with the APOL1 high-risk gene polymorphism and those with sickle cell trait (SCT) are more likely to develop ESKD.
-SCT associates with a faster decline in estimated glomerular filtration rate (eGFR) with aging, incident chronic kidney disease (CKD), and a relative risk of ESKD that is at least twofold higher than those with a normal hemoglobin in the nondonor population.
-The study used the publicly available dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study, which was a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study. RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama- Birmingham. Donations took place between 1963 and 2007.
-The results from this small case series suggest the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
-Sickle cell disease (SCD) nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease in many.
-In SCT, 30–40% of the red blood cell hemoglobin content is hemoglobin S (HgbS) and this level is sufficient to cause complications such as hematuria and impaired concentrating ability.
-Renal microangiographic studies show SCT carriers can indeed experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed in SCD.13
-The absolute risk of ESKD in those with SCT, however, was only 8.5 per 1000 person years.
– Masimango et al. suggested a synergistic association between SCT and APOL1
high-risk genotypes on reduced eGFR defined as <60 mL/min/1.73m2.
-Outcomes for recipients of deceased donor kidneys from SCT donors has not been reported.
-The prevalence of SCT in African-American donors was 9/822 and 6/7482 white
donors, yielding a prevalence of 11/1000 and 0.8/1000, respectively.
The corresponding rates in the general populations are 73.1/1000 in AA and 3/1000 in Whites.
-In all, this preliminary data suggests that donors with SCT who were allowed to donate have done well, but may develop proteinuria which can be an early sign of kidney disease and hence more data is needed. Excluding potential kidney donors with SCT, particularly older ones, should be revisited.
What is the level of evidence provided by this article?
Level 3
Outcomes of kidney donors with sickle cell trait: A preliminary analysis
Screening for sickle cell is not a routine workup in kidney donor evaluation only 34% of transplantation centers do screening and some centers will reject donors with sickle cell trait just of unclear data regarding risks for CV morbidity and risk for proteinuria and ESRD. It’s well known that SCD is associated with the risk of proteinuria, tubular dysfunction, and ESRD because of hyperperfusion in the cortex and hypoperfusion in the medulla caused by abnormal HB S but for SCT correlation is still unclear.
Aim of the study:
a case-control study (level of evidence III) evaluating the immediate and long-term outcomes of live kidney donors with sickle cell trait compared to matched donor controls.
Methods:
+ve sickle cell trait donors from records of the RELIVE study were contacted.
post-donation hypertension, CV disease, proteinuria, and GFR were assessed.
Results:
Nine were African Americans, six were White, and two were listed as other or unknown ethnicities. Patients were followed-up period for 18.2 ± 10.5 years:
-both groups showed no difference regarding the development of hypertension or cardiovascular disease.
-No donor with SCT developed an eGFR <30 mL/min or kidney failure.
-SCT was associated with an increased risk of proteinuria.
Conclusion:
till now there is still suspicion regarding accepting donors with SCT but as regards this small number of a donor who did well regarding eGFR and hypertension but developed proteinuria, it looks safe to accept but More data is needed.
Limitation:
African Americans (AA) with SCT are more likely to develop ESKD, however AA potential donors are not routinely screened for SCT despite the associated risk of ESKD.
Available data about the outcome of kidney donors with SCT is not sufficient.
SCD nephropathy manifest with proteinuria, urinary concentrating defects, progressive kidney disease and hematuria.
SCT carriers may develop renal medullary damage but less than that in SCD.
Several studies showed association between SCT and CKD, but the outcome of live kidney donor with SCT is unclear.
83% of transplant centers don’t screen potential donors for SCTand 18% of centers exclude donors with SCT or SCD
This study aims to evaluate immediate and long-term outcome of kidney donors with SCT compared to propensity score matched donor controls without SCT, it included 17 donors with SCT and 68 matched donors without SCT
Data were obtained from dataset from RELIVE study.
The study suggested that donors with SCT and those without have the same risk of HTN, CVD and decreased GFR but donors with SCT were at higher risk of developing proteinuria which may indicate early kidney disease.
The favorable outcome of this study may be due to careful choice of donors with good health to donate.
Further studies are needed to determine the outcome of live kidney donor with SCT
Limitations:
Small sample size
No data available about tests done to diagnose SCT
Results of GFR should be interpreted cautiously due to small sample size
Urine specific gravity and urine microscopy were not available so donors with hematuria or concentrating defects are not determined.
Level 3, (Case control study)
SCT is a silent disease. SCT is more common among African-American population and associated with a higher risk of end-stage kidney disease compared to white. The prevalence of the Apol1 in African-Americans is 11–13% and 8– 9% for the SCT.
Screening for SCT is not a standardized across transplant centers. Only 34% of US transplant centers actually screen potential donor candidates for SCT. BUT is wider screening for SCT should be considered all donors? Few studies showed that patients with SCT have faster decline in estimated glomerular filtration rate with aging, incident chronic kidney disease, and twofold higher risk of ESRD compared to those with a normal hemoglobin in the nondonor population.
The provided study evaluated dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study. Donations took place between 1963 and 2007.
Donors were asked if they developed diabetes, hypertension, kidney disease, CVD, cancer, and other conditions and were also asked to respond to quality-of-life surveys.
RESULTS
Out of 8922 screened for SCT, 17 donors had SCT: nine are African-American, six are White, two listed as other or unknown ethnicity.
Long-Term Outcomes
After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR < 60 mL/min/1.73 m2.
None of the donors with SCT developed an eGFR. The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls; univariable relative risk 5.71.
In summary, the results from this small case series suggest that the risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
What is the level of evidence provided by this article?
Level of evidence 3
Will this article change your practice and why?
Results of this study would not change screening plan for donors, as SCT is very rare and very small percentage of population is affected and this study showed no higher risk of ESRD, hypertension or CVD with kidney donation. However in areas with high prevalence of SCD, screening should be done, so that unexplained proteinuria in kidney donor with confirmed SCT could be attributed to SCT.
Summary:
Introduction:
· Sickle cell disease (SCD) nephropathy is characterized by cortical hyperperfusion, medullary hypoperfusion, and an augmented vasoconstrictive response to systemic and regional stresses. Notably, hyperfiltration is not a feature of SCD. Clinically, SCD nephropathy manifests with proteinuria and urinary concentration.
· In SCT, 30–40% of the red blood cell hemoglobin content is hemoglobin S (HgbS), and this level is sufficient to cause complications such as hematuria and impaired concentration. Renal microangiographic studies show SCT carriers can indeed experience renal medullary damage over time secondary to sickling, albeit markedly less than that observed inSCD
· African-Americans (AA) have a higher risk of end-stage kidney disease (ESKD) than Whites.
· African-Americans with the APOL1 high-risk gene polymorphism and sickle cell trait (SCT) are more likely to develop ESKD screening for SCT in African-American kidney candidates ESKD in those with SCT is almost identical to those with APOL1 high-risk gene polymorphism.
· Kidney Disease Improving Global Outcomes (KDIGO) Live Donor Practice Guidelines recognized the deficiency of data in this area. In addition, they identified expanding knowledge about donors with SCT as a future research direction.
METHODS:
Study Population
We used the publicly available dataset from the Renal and Lung Living Donor Evaluation (RELIVE) Study, a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study. The exposure of interest is SCT. None of the participating centers accepted donors with sickle cell disease. It needs to be clarified from
the public dataset how many donors screened for SCT or why those with SCT were screened. Since SCT is most common in African-Americans, we also determined the ethnicity of the recipients in related donors
Statistical Analysis
SCT was compared using Fisher’s exact test for categorical variables and the Wilcoxson rank-sum test for continuous variables. In addition, ascertained propensity score matching without replacement with a ratio of one SCT donor: four donor controls without SCT using a caliper of 1 and matching criteria of age (in years), gender, ethnicity, weight, eGFR at donation, related versus unrelated, study center, and year of contribution.
All analyses were performed on Stata version 17.0 (Stata- Corp LLC)
RESULTS:
General Characteristics:
Ø There were 8820/8922 (98.8%) donors who provided field for the presence of SCT
Ø There were 17 donors with SCT: nine are African-American (AA), six are White, and two are listed as other or unknown ethnicity.
Ø Of the nine AA donors with SCT, eight donated to related AA recipients, and 5/6 White donors donated to related White recipients. Pre-donation hemoglobin was 13.6 g/dL (IQR 12.3, 14.9) in donors with SCT compared to 14.0 g/dL (IQ R 13.1, 15.1) in controls, P = .17.
Ø Donors with SCT had a lower fasting plasma glucose; 84 versus 92 mg/dL; P = .002, but were otherwise similar to those without SCT
Long-Term Outcomes:
Ø Death (5.9%)
Ø CVD(11.8%)
Ø hypertension (29.4%)
Ø CKD <60 mL/min/1.73 m2(31.3%)
Ø proteinuria (28.6%)
The results from this small case series suggest that reduced eGFR, hypertension, and cardiovascular disease risks are similar in those with and without SCT. Still, donors with SCT are more likely to develop proteinuria.
Conclusion :
This preliminary data suggests that donors with SCT who were allowed to donate have done well but may develop proteinuria, which can be an early sign of kidney disease, and hence more data is needed. Therefore, excluding potential kidney donors with SCT, particularly older ones, should be revisited.
Study limitation :
This case series is limited by its small size. Other rules include the need for more information in the public dataset on how to ascertain the diagnosis of SCT and how many donors were tested for SCT.
Three large studies have demonstrated a link between SCT and CKD:
Naik et al. showed that SCT carriers (from five large observational studies) :
1- albuminuria; 31.8% , non carriers, 19.6%
2- CKD, 20.7% versus 13.7%.
3-Stroke was 5.4% versus 2.6% in non-carriers.
Masimango et al.:
A synergistic association between SCT and APOL1 high-risk genotypes on reduced eGFR was defined as <60 mL/min/1.73m2.
Olaniran et al. demonstrated that in 9733 subjects with an eGFR >65 mL/min/1.73 m2 at baseline, eGFR declined by 1.27 mL/min/1.73 m2/year in those without SCT, 1.67 mL/min/1.73 m2/year in those with SCT, and 2.5 mL/min/1.73m2/year in the 230 participants with SCD.
SUMMARY
Introduction:
African American are known to be more at risk of CKD particularly from the established effect of mutation APOL1 gene and coupled with the increase prevalence of sickle cell disease and trait then the tendency to come down early with CKD or ESRD among them is more. However, despite this possibility, only 34% of transplant Centre in US screen for SCT in potential donors.
Aim of the Study:
Method:
Results:
Conclusion:
The study showed that, the risk of reduction in GFR, or development of hypertension or CVD among donor SCT or without SCT is similar with the exception of higher number of donors with SCT having proteinuria.
Limitation
Level of evidence is 3 because the subject has the outcome of interest
This study highlights the short and long term outcomes of living donors with SCT
Populations
8922 living donors
From 1963 to 2007
Survey was accomplished between 2010- 2012 about incidence of
DM- Hypertension- CKD CVD- cancer
among living donors
Results
17 LD with SCT(9 AA 6wight 2 other ethnicities )
After propensity score matching 4: 1 ( non SCT : SCT)
there were no difference of results between the two groups according to : age – gender- ethnicity BMI- donation year..
Long term outcomes
After a mean follow- up ( 18 years), living donor with SCT had
5.9% death
11.8% CVD
29.4% Hypertension
31.3% reduction of eGFR less than 60
All of above are similar and with no significant importance when compared with control group
However, proteinuria was found in 28.6% among LD with SCT vs 5% in LD without SCT
RR 5.7% 95% CI P=0.1
Clinically, SCD nephropathy manifests with proteinuria, urinary concentrating defects, and progressive kidney disease
There are 3 large studies demonstrate the relation between SCT and the incidence of CKD
It is perhaps constructive to think about candidates with SCT similar to how we think about AA donor candidates with high-risk APOL1 gene polymorphisms
Some limitations
Level of evidence 3( as professor Ahmed explained)
In our practice
We may think about expand living donors pool by accepting donors with SCT
However, for sure, we need other large studies to confirm the validity of these results
V. Outcomes of kidney donors with sickle cell trait: A preliminary analysis
Please summarise this article in your own words
Introduction
The prevalence of sickle cell trait (SCT) in African-Americans is 8–9%; however, screening for SCT is not commonly done.
Screening potential donors for SCT is done in only 34% of US transplant centers; centers vary widely in accepting those with SCT for donation.
Wider screening is needed as SCT is associated with a faster decline in eGFR with aging, incident CKD, & a relative risk of ESRD ( 2 fold higher than those with a normal Hb hemoglobin in non-donors).
KDIGO identified expanding knowledge about donors with SCT as a future research trend.
The study
The outcomes (short & long-term) of a small case series of LKDs with SCT compared to matched donor controls without SCT.
Study population
Dataset from RELIVE Study (8922 LKDs between 1963 & 2007) was used.
Exposure & outcomes
None of the participating centers accepted donors with SCD; however, it is unclear from the dataset how many donors were screened for SCT or why those with SCT were screened.
The ethnicity of the recipients was determined in related donors.
Post-donation HTN was defined as use of medications or BP = or more than 140/90 mmHg.
CVD was defined as a diagnosis of MI, HF, stroke, or need for coronary or peripheral arterial interventions.
Proteinuria was defined by the presence of 1 or more of the following:
– urine dipstick protein !1+ or more
– urine protein/osmolality ratio >0.42
– urine random protein >15 mg/dL
– 24-hour protein >300 mg/day.
CKD-EPI equation was used to estimate GFR.
ESKD defined by the need for dialysis or being listed for or a kidney transplant.
Statistical analysis
Stata version 17.0 (Stata-Corp LLC) was used for analysis.
Results
General Characteristics
Total number of donors: 8922
Field for the presence of SCT was present in 8820 (98.8%).
The number of donors with SCT: 17 (9 African-American, 6 White, 2 unknown ethnicity).
Donors with SCT had a lower FBG; otherwise similar to those without SCT.
Pre-donation Hb was 13.6 g/dL versus 14.0 g/dL in controls.
Long-Term Outcomes (a mean follow-up of 18.2± 10.5 years):
Deaths: 1(5.9%)
CVD: 2(11.8%)
HTN: 5 (29.4%)
eGFR <60 mL/min: 5 (31.3%)
eGFR <30 mL/min: None
ESKD: None
The proportion of these outcomes were similar between SCT donor & controls.
No urinary protein quantitative in any SCT donor; 3 had urine dipstick (1, trace, 1, 2+, 1, 3+)
Serial creatinine measurements were available in 11/17 (64.7%) of cases & 37/68 (54.4%) of controls.
Donors with SCT had an eGFR increase of 2.13 mL/min/year versus 1.24 mL/min/year in controls.
Discussion
Risks of reduced eGFR, HTN, & CVD are similar in SCT & controls.
Donors with SCT are more likely to develop proteinuria.
SCD nephropathy is characterized by cortical
hyper-perfusion, medullary hypo-perfusion, & augmented vasoconstrictive response to systemic & regional stresses.
Hyperfiltration is not a feature of SCD.
Clinical manifests of SCD: proteinuria, urinary concentrating defects, & progressive kidney disease.
In SCT, 30–40% of the RBC hemoglobin content is HgbS ; a level sufficient to cause complications such as hematuria & impaired concentrating ability.
Renal medullary (dt sickling) damage can occur over
time in SCT; but less than in SCD.
Studies linking SCT & CKD:
1. Naik et al: SCT carriers were more likely to develop albuminuria (31.8% vs 19.6% in non-carriers) , were more likely to lose > 3 mL/min / year of eGFR (22.6% vs 19.0%) & were also more likely to develop CKD (20.7% versus 13.7%).
2. REGARDS study (739 participants): risk of ESRD with SCT was 5.4% versus 2.6% in non-carriers. The absolute risk of ESRD was only 8.5/1000 person years. Interestingly, this relative
3. Masimango et al.: synergistic association between SCT & APOL1 high-risk genotypes on reduced eGFR (<60 mL/min).
4. Olaniran et al (9733 subjects with baseline eGFR >65 mL/min): eGFR declined by 1.27 mL/min/ year in those without SCT, 1.67 mL/min/year in those with SCT, & 2.5 mL/min/year in the 230 participants with SCD.
5. Rehman et al: a single case report by of a 35-year-old who donated to his 22-year-old brother who has SCT as well; both had excellent kidney function 4 years later.
6. Mandelbrot et al: 83% of transplant centers did not have a policy for screening for SCT or SCD (a survey of US transplant centers); 18% of centers would not consider candidates with SCT.
KDIGO recognized the deficiency in this area and identified expanding knowledge about donors with SCT as a future research direction.
CDC website dedicated to SCD & SCT states that those with SCT can donate blood, tissue & organs.
Limitations
The size of case series is small.
Lack of information in dataset on how the diagnosis of SCT was made & how many donors were actually tested for SCT.
The lower prevalence of SCT in RELIVE donors may reflect that many candidates with SCT were perhaps not allowed to donate and many if not most were not screened.
The 17 donors with SCT who donated reflect a high selection of those who have had no any signs of kidney disease such as concentrating defects or hematuria.
Excluding kidney donors with SCT should be reviewed.
More information regarding these outcomes can be expanded if AA donors could be invited back for SCT screening & formal assessment of kidney function.
==========================
What is the level of evidence provided by this article?
Level V
Please summarise this article in your own words
It is not routine to screen potential donors for sickle cell trait, and many centers would decline these patients from donation, because they are 2 fold increased risk of ESRD.
the study reports short and long term out come in 17 living donor candidates extracted from RELIVE study, compared to donor with no SCT.
Primary out come: proteinuria (defined by urine dipstick +1 or more,urineprotein/osmolality ratio >0.42, urine random protein >15 mg/dl or 24 hours protein urine >300 mg/day) , HTN (B/P equal or more than 140/90 mmHg or use of antihypertensive medications), ESRD (need of dialysis or on the waiting list for transplantation), and cardiovascular diesease(MI,heart failure, need for coronary or peripheral intervention, and stroke).
Results:
The patients with SCT had lower fasting glucose level (P value =.002)
No difference in hemoglobin level, GFR, ICU admission post donation , blood transfusion , volume of intra-operative blood loss in both groups.
There were no difference in primary outcome variables but proteinuria was more in the SCT donors (P value= .01).
Limitations:
Small number of patients.
Lack of public data on SCT diagnosis, and how many donors tested for it.
Difficult/ lack of proper data required for better interpretation.
Conclusion: the healthiest donors with SCT are able to donate kidney with favourable outcomes, inspite of higher risk of proteinuria.
African americans should be screened for SCT when they scren for APOL1 gene, and give more comprehensive informed consent, and better evaluation in large study.
What is the level of evidence provided by this article?
case control cohort out come study, level IIc
The aim o the study ;
To evaluate the outcome of kidney donor with sickle cell trait
Population;
17 donors with SCT: nine are African-American (AA), six are White, two listed as other or unknown ethnicity.
The method ;
17 kidney donors with SCT were compared to propensity score matched donor controls
on mortality, reduced eGFR, proteinuria and kidney failure.
Statistical analysis;
Baseline characteristics are reported as frequencies and proportions for categorical variables and median and interquartile range (IQR) for continuous ones.
Differences between donors with and without SCT were compared using Fisher’s exact test for categorical variables and the Wilcoxson rank-sum test for continuous variables.
The generalized linear mixed model used eGFR as the dependent variable, SCT as the independent variable and employed a random intercept plus random slope model and an unstructured covariance option. All analyses were performed on Stata version 17.0 (Stata-Corp LLC)
The result;
1-No donor with SCT developed an eGFR <30 mL/min/1.73 m 2 or kidney failure.
2-SCT was, however, associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 – 22.7), P = .01.
The limitation o the study ;
1-small size.
2-The lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
Conclusion;
1-this preliminary data suggests that donors with SCT who were allowed to donate have done well, but may develop proteinuria which can be an early sign of kidney disease and hence more data is needed.
2- This small and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort of donors with SCT
2-Excluding potential kidney donors with SCT, particularly older ones, should be revisited. Nevertheless, the favorable outcomes reported here may also be indicative of the fact that only the health candidates with SCT were able to donate.
3-AA donor candidates support testing for APOL1 gene polymorphisms and perhaps should be screened for SCT as that would lead to a more comprehensive informed consent process, higher quality research in this area and importantly the signal for proteinuria can be studied more carefully.
What is the level of evidence provided by this article?
Level III ( case controlled study )
Introduction
Patients with sickle cell disease (SCD) are disqualified from donating because of a high prevalence of developing CKD. The RR of developing CKD is also slightly higher in patients with SCT as compared to the non-carriers. African Americans have a higher prevalence of SCT due to its evolutionary protective effects against malaria. The prevalence of APOL1 gene polymorphism is 11-13%. The prevalence of SCT is 8-9%. The RR of developing ESRD is similar in both populations but very few centers screen for SCT and there are no guidelines regarding whether to accept these individuals as donors or not.
Methodology
This was a case control study that looked at the short and long term outcomes of 17 kidney donors with SCT and compared them to propensity score matched donor controls without SCT. Both the SCT donors and non-SCT donors were selected from the RELIVE study.
The RELIVE study collected data for living kidney donors from 3 centers from 1967 to 2007. The database had 8922 living kidney donors from which 17 donors with SCT and 68 donors without SCT were identified and followed up for an average of 18.2 years.
The exposure of interest was SCT.
The outcome measures were the development of:
Majority of the donors with the SCT were African American (9/16) and 6/16 were Caucasians (6/16). Majority of the SCT donors donated to their relatives.
Outcomes
The development of post donation HTN, CVD and CKD (eGFR of < 60 mls/min) was similar between SCT donors and donors without the SCT
However, the development of proteinuria was higher in SCT donors (28.6% compared to donors without SCT (5%)
It is postulated that SCT carriers can experience renal medullary damage over secondary to sickling albeit slower than those with SCD
3 large studies have demonstrated a link between SCT and development of CVD
Naik et al showed that individuals with SCT were more likely to develop albuminuria and CKD (eGFR< 60 mls/min) as compared to the non-carriers. The carriers of SCT were not at an increased risk of developing HTN and CVD which was what was found in this study.
In the REGARDS trial, the risk of developing ESKD was similar in patients with APOL1 gene polymorphism and SCT carriers. However, the risk did not increase if the patients had both APOL1 gene polymorphisms and SCT carrier state.
A study by Masimango et al suggested a synergistic association between SCT and APOL1 high risk gene mutation on reduced eGFR independent of albuminuria.
A study by Olaniran demonstrated a higher decline in GFR in SCT carriers versus non-carriers.
There have been only case reports of outcomes of SCT donors.
This was the first study that looked at SCT donors and compared them to non-SCT donors.
A limitation of this study was the small size and no data available as to how the diagnosis of how the diagnosis of SCT was made
Larger prospective studies are needed to assess the risks of developing CKD, CVD, HTN and proteinuria in SCT donors so that appropriate guidelines are formulated regarding SCT donors
Level of Evidence
This was level III evidence as the it was a case control study with the exposure of interest being SCT and the outcomes were development of CKD, HTN, CVD and proteinuria. The cases were compared to propensity score matched controls
Outcomes of kidney donors with sickle cell trait: A preliminary analysis.
Still this point of long term outcome of kidney donors with SCT has not being cleared and no identifying knowledge about this .
African-American are higher risk to develop ESRD than white people, and also has higher incidence to develop SCT and mainly due to association of APOL 1 gene polymorphism.
It is not routine in many transplant center to screen donors for SCT, in this study try to signify the immediate and long term effect of SCT on mortality, reduced eGFR, proteinuria and kidney failure.
Method:
We compared 17 kidney donors with SCT to propensity score matched donor controls on mortality, reduced eGFR, proteinuria and kidney failure.
By collecting data from donors by phone contact or e-mail , check mortality rate and HTN defines as as self-reported use of antihypertensive medications or BP ≥140/90 mmHg .
Cardiovascular disease (CVD) was defined as a diagnosis of myocardial infarction, heart failure, stroke, or need for coronary or peripheral arterial intervention.
CKD-EPI to assess kidney function and ESRD defined as needing for RRT or KTX listing.
Proteinuria defined as urine dipstick protein ≥1+, urine protein/osmolality ratio >0.42, urine random protein >15 mg/dL, or 24- hour protein >300 mg/day.
Result:
After propensity score matching of one donor with SCT: four donors without SCT, there were no significant differences between cases and controls.
After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive, developed hypertension or cardiovascular disease were similar except proteinuria was common than in SCT donors.
Strength points:
This study provided preliminary data for future larger prospective studies.
Limitation:
-small size.
-lack of information in the public dataset on how the diagnosis of SCT.
Conclusion:
Study give us preliminary data about out comes of kidney donors with sickle sell trait and they were associated with risk of proteinuria which may be risk of CKD, but still need large prospective studies to clarify this point.
African-American donor candidates support testing for APOL1 gene polymorphisms and should be screened for SCT .
Level of evidence III(case-control study).
Screening for sickle cell trait (SCT) is not done in prospective kidney donor sin majority of transplant centres and those with SCT are rejected as donors, considering faster fall in GFR, increased risk of CKD and ESRD development in such patients, especially if of African-American ethnicity.
The study was conducted based on dataset from RELIVE Study, comparing 17 kidney donors with SCT with 4 times matched donors (between 1963 and 2007) with respect to mortality, eGFR reduction, proteinuria, and renal failure.
Out of 17, 9 were of African-American ethnicity.
After a follow up of 18.2 mean years, the risk of hypertension and cardiovascular disease was similar and none of the SCT donors developed eGFR<30 ml/min. Donors with SCT had higher proteinuria (28.6% versus 5%).
The study had limitations like: small size, lack of data regarding testing of SCT, small number of serum creatinine measurements, urine microscopy and specific gravity were not available in data.
The donors with SCT have similar parameters with respect to reduction in GFR, ESRD and mortality. They may develop proteinuria, which may be an early marker of kidney disease. So, donors with SCT can be considered, if other parameters are met for organ donation, especially in older donors.
Level of evidence: Level III – Case-control study
SCT screened in some center as a routine, while other not, and some center decline donors with SCT from donation.
The prevalence of SCT in African American AA, was 1/1000, compared to 73/1000 in non-donor AA.
Donors with SCT were younger; 33 VS 35 years in controls, as fellow; 9 were AA, 6 were white, and 2 as others.
AA have higher risk factors of ESKD compared to whites, with no obvious scientific explanation, and those with APOL1 as well as SCT are more risky to develop ESKD, despite this risk , SCT screening in USA for kidney donors are not routinely done in all transplant centers.
The evidence is to proceed for donation or not for SCT donors are not yet clearly available, KDIGO , recognise a deficient data in this area.
Methods;
Study population;
Data used are from RELIVE study, involving 8922 living kidney donors, from 1963 to 2007.
HTN, DM, kidney diseases, and CVD are involved in the study.
Statistical analysis;
Donors with SCT and those without SCT differences were studied using Fishers exact test for categorically variables and the Wilson rank-sum test for continuous variables.
The ratio of SCT donor to controls was 1:4, with similar data; age, sex, ethnicity, weight, eGFR at donation, related VS untrlated.
Results:
2.SCT donors, had a lower FBG; 84 VS 92; P=.002,
3.Of 9 SCT donors; 8 were donoated to AA recipients, 5/6 white donors donated to related whites recipients.
4.Predonation Hb was13.6 g/dl in SCT donors compared to 14 gm/dl in non-SCT donors .
5.There were no differences between between cases and controls, according to the propencity score matching of 1 SCTDx/SCTnon-Dx.
6.Cases and controls were highly comparable on lowest postoperative hemotocrit, need ICU admission or BT, and volume of intraoperative blood loss.
7.The proportion of SCT Dx undergoing laparoscopic left nephrectomy was similar to that of controls.
Long term outcome:
Discussion:
The risk of reduced eGFR, HTN,CVD, in those with SCT and non-SCT donors are similar, but SCT donors are more likely to develop proteinuria.
Sickle cell disease nephropathy is characterized by cortical hyperperfusion, medullary hypoperfusion, and an overall augmented vasoconstrictive response to systemic and regional stresses,(note; hyperfilteration is not a feature of SCD).
SCD manifest by proteinuria, urinary concentrating defects, and progressive kidney disease.
In SCT, 30-40% of red cell Hb, is HgbS, and this level is sufficient to cause complication such as haematuria, and impaired concentrating ability.
Renal microangiographic study show medullary damage over time secondary to sickling , and markedly less than that of SCD.
Studies that link between SCT and CKD;
In all , this data suggests that SCT donors who were donate have done well , but may develop proteinuria, which can be early sign of kidney disease.
Excluding potential donors with SCT, particularly older ones . should be revisited, but healthiest one is advisable.
Level of the study;
RCT level (III)
Hi Dr Kamal,
That is a very good summary, that is not difficult to write. I am looking for the strengths and limitations of this publication to be described the way a senior fellow and experienced clinicians would do. Only then would one be able to determine whether to adopt lessons from publications to clinical practice, the first step in the implementation of principles of evidence-based medicine.
Ajay
Screening for SCT in African-American kidney candidates is not commonly done despite the fact that the relative risk of ESKD in those with SCT is almost identical to those with APOL1 high-risk gene polymorphism. The outcome of kidney donors who harbor the SCT need to evaluated.
Study population:
Participant from (RELIVE) Study, which included 8922 living kidney donors from 3 transplant centers.
Donations took place between 1963 and 2007.and donors were contacted in 2010–2012.
17 live kidney donors with SCT compared to 68 propensity score matched donor controls without SCT. The matching 1:4.
Exposure The exposure of interest is SCT.
The participating center excluded donors with sickle cell disease.
Outcomes; Post-donation HTN; CVD; Proteinuria and ESKD.
Results:
The prevalence of SCT in African American (AA) donors was 11 per 1000 compared to 73 per 1000 in non-donor AA.
Donors with SCT were younger, 9 were AA, 6 were White, and 2 unknown ethnicities.
The follow-up period of 18.2±10.5 years.
The proportions of donors with SCT and controls who were similar for HTN and CVD.
SCT donors have increased risk of proteinuria; RR 5.71
No donor with SCT developed an eGFR <30 mL/min/1.73 m2 or kidney failure.
Donors with SCT had an overall eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73m2/year in controls.
Conclusion: The risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria. This small case series suggest that donors with SCT should perhaps be considered more often.
level 3, retrospective, case- control study
Dear Dr Hadeel,
That is a very good summary, that is not difficult to write. I am looking for the strengths and limitations of this publication to be described.
Ajay
This article discuss the outcome of kidney donation in patients with sickle cell traits.
Sct is more prevelance in african amircan
The study found that patient with sct have no increase risk to develop Esrd ,CVD, or hypertension compare with other donors without scd trait but have an increase risk for developing protienurea.
This case control study has multiple limitations:
1_small number of patients with sct.
2_lack of information about the diagnosis of sct.
3_the real number of donors who have or tested for sct.
Level 3 case control study.
Will this article change your practice and why?
Despite the limitations present in this study ,it may changing our criteria to accept patient with sct especially older patient and we live in area where scd is not uncommon (3% of population) and test for sct is available and not cost effective .
What are the problems encountered when you use the data registry for data collection?
multiple problems are present .:
Inconsistent data collection standards
Context of data collection.
Complexity
Changes to defenetions and polices and maintaining data comparability
Lack of some data
The origon data may not accurate or fake .
That is a fantastic analysis of this article, dear Dr Abdulla Hindawy. I am impressed.
Request to you:
Please type abbreviations ‘sct’ in capital letters as SCT, to save me discomfort of reading incorrect syntax.
Methode:
We looked at the data from 9822 LKD that were participants in the RELIVE project ( donation 1963-2007).
Potential donors who had SCD were excluded from the donation process, however, there was a paucity of data about the screening strategy used for SCT.
Post-donation hypertension is defined by the use of anti-hypertensives or a blood pressure reading of more than 140/90. Reduced eGFR, hypertension, and cardiovascular disease risk were all similar in SCT donors and non-SCT donors, although SCT donors had a greater likelihood of developing proteinuria.
Results:
SCT has been associated with a faster decline in estimated glomerular filtration rate (eGFR) with ageing, incident chronic kidney disease (CKD), and a relative risk of ESKD that is at least twofold higher than those with normal haemoglobin in the nondonor population. Perhaps a wider screening should be considered, as this is the case because SCT has been associated with these factors. This is a small case series consisting of 17 live kidney donors that reports on the immediate and long-term effects of SCT in comparison to propensity score matched donor transplants.
Conclusions:
According to the findings of this limited case series, the risks of lower eGFR, hypertension, and cardiovascular disease are comparable in those with and without SCT. On the other hand, donors with SCT are more likely to develop proteinuria, which may be an early symptom of kidney disease.
Reconsidering whether or not to exclude prospective kidney donors with SCT, especially older ones, is something that has to be done.
Evidence to the Level of:
– Level 4 ( case series)
Thank You
See my comments above
Hmmm, level 4?
-Introduction
African-Americans having the APOL1 high-risk gene polymorphism and those with sickle cell trait are more susceptible to develop ESRD.
Testing for APOL1 gene polymorphisms in potential African-American donor candidates is increased , screening for SCT in African-American kidney candidates is not frequently done in spite that the relative risk of ESRD in SCT cases is similar to those with APOL1 high-risk gene polymorphism.
Transplant centers policy regarding including SCT cases as donors are variable .
SCT is accompanied with rapid decrease in eGFR with aging, incident CKD and relative risk of ESRD.
KDIGO noticed insufficient data in this area .
Methods
Data of living kidney donors in RELIVE study was used within 44 years .
There were 17 donors with SCT 9 were African-American (AA), six were white, two of unknown ethnicity. Donors with SCT had a lower Fasting blood sugar than those without SCT.
Propensity score matching of one donor with SCT: four donors without SCT was done on age , gender, ethnicity, weight ,eGFR at donation, relationship to the recipient, no significant differences between cases and control were detected.
Long term outcomes
Follow-uping for 18.2±10.5 years, one donor with SCT
died, two developed CVD, five developed hypertension, and five reached an eGFR <60 mL/min/1.73 m2 .
None of the donors with SCT developed an eGFR <30 mL/min/1.73 m2or ESKD.
One with trace proteinuria developed 20.4 years from donation, one with 2+,11.7 years from donation and one with 3+, 34.9 years from donation.
Donors with SCT had an eGFR increase of 2.13 mL/min/1.73 m2/year compared to 1.24 mL/min/1.73 m2/year in controls.
Discussion
Reduced eGFR, hypertension, and cardiovascular disease risks are similar in those with and without SCT, but donors with SCT are more prone to develop
Proteinuria.
SCD nephropathy presents with proteinuria, urinary concentrating defects, and progressive kidney disease .
SCT carriers can suffer renal medullary affection due to sickling more than SCD cases.
Studies concluded that SCT are more likely to suffer of proteinuria , lower e GFR and CKD risk.
Masimango et al. supposed a similar association between SCT and APOL1 high-risk genotypes on reduced eGFR defined as <60 mL/min/1.73 m2.
Others noticed higher rate of decline of GFR in cases with SCT compared to non SCT.
There are sparse data on outcome of donation of SCT case to SCT recipient.
CDC decided that SCT can donate blood ,tissue and organs.
ESKD cases that could have been avoided in AA donors if no SCTdonors were accepted is 10 and for APOL1 high-risk alleles a total of 14 cases of ESKD would have been avoided.
The limitations of this study is being small ,lack of methodology of SCT detection.
Screening newborns for SCT wasnot applied until 2006.
17 donors with SCT indicated highly selected candidates whom did not have any signs of kidney disease.
Donors having SCT whom donated were stable , but may have developed proteinuria as an early sign of renal affection .
AA donors need testing for APOL1 gene polymorphisms and possibly screening for SCT as well.
-level of evidence is IV
Thank You
See my comments above
Hmmm, level 4?
Outcomes of kidney donors with sickle cell trait: A preliminary analysis
Summary of the Article
This study, reported on immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT. Cases ‘data was retrieved from the Renal and Lung Living Donor Evaluation (RELIVE) Study in the period between 1963 and 2007.
Study Outcome
1. After a median follow up of 18.2+/- 10.5y; 1died(5.9%), two (11.8%) developed CVD, five (29.4%) developed hypertension and five(31.3%) developed an eGFR <60. None of the donors developed an eGFR below 30.
2. The proportion of donor controls reaching these outcomes were similar with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls.
3. The risks of reduced eGFR, hypertension, and cardiovascular disease are similar in those with and without SCT, but donors with SCT are more likely to develop proteinuria.
Limitations of the Study
1. This case series is limited by its small size.
2. No donor had quantitative urinary protein estimate available, only 3 donors had urine dipstick for protein.
3. The lack of information in the public dataset on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
What is the level of evidence provided by this article?
This is a case series study
Level of evidence grade V
Thank You
See my comments above
Hmmm, level 5?
INTRODUCTION
-African-Americans (AA) have a higher risk of (ESKD) compared to Whites.
– African-Americans with the APOL1 high-risk gene polymorphism
and those with sickle cell trait (SCT) are more likely to develop ESKD.
The prevalence of the African-Americans is 11–13% and 8– 9% for the latter.3,4 While there is a growing advocacy for testing for APOL1 gene polymorphisms in potential African-American donor can dilates, screening for SCT in African-American kidney candidates is not commonly done despite the fact that the relative risk of ESKD in those with SCT is almost identical to those with APOL1 high-risk gene polymorphism.
-Wider screening perhaps should be considered as SCT has been associated with a faster decline in estimated (eGFR) with aging, incident chronic kidney
– (KDIGO) Live Donor Practice Guidelines recognized the deficiency of data in this area and identified expanding knowledge about donors with SCT as a future research direction. 8 Herein, we report on the immediate and long-term outcomes of a small case series of 17 live kidney donors with SCT compared to propensity score matched donor controls without SCT.
METHODS
-RELIVE Study, which was a National Institute of Allergy and Infectious Diseases (NIAID) sponsored study:
-RELIVE included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama-Birmingham.
– Donations took place between 1963 and 2007
-Donors were contacted in 2010–2012 by mail requesting participation
in the RELIVE Study.
– Donors were asked if they developed diabetes, hypertension, kidney disease, CVD, cancer, and other conditions and were also asked to respond to quality-of-life surveys
-In all, post donation ascertainment of outcomes came from donor surveys, participating centers’ own records, review of medical records provided by the donors themselves and also from the recipients.
-Proteinuria was defined by the presence of one or more of the following: urine dipstick protein ≥1+, urine protein/osmolality ratio >0.42, urine random protein >15 mg/dL, or 24-
hour protein >300 mg/day.
-Cardiovascular disease (CVD) was defined as a diagnosis of myocardial infarction, heart failure, stroke, or need for coronary or peripheral arterial interventions.
Long-Term Outcomes
-After a mean follow-up of 18.2±10.5 years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed hypertension, and five (31.3%) reached an eGFR <60 mL/min/1.73 m .
-None of the donors with SCT developed an eGFR <30 mL/min/1.73 m 2
or ESKD.
-SCT was, however, associated with increased risk of proteinuria; RR 5.71 (95% CI 5.7 – 22.7), P = .01.
-This small and preliminary case series suggest that donors with SCT should perhaps be considered more often provided they were aware of the lack of evidence to support liberal acceptance and that these outcomes reported here likely represent a healthy cohort of donors with SCT.
Limitation
1-Small size
2- Lack of information on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT.
CONCLUSTIONS
-Donors with SCT were doing well with the exception of increased proteinuria which is an early sign of kidney disease.
-Risks of reduced eGFR, HTN, and CV disease were the same and.
-Excluding SCT from donation therefore should be revised particularly in older donors – -AA donors should be screened for SCT as for APOL1 gene for more studies of proteinuria.
The leve; of evidence (4)
Thank You
See my comments above
Introduction:
Most transplant centers do not screen kidney donor candidates for sickle cell trait, and many decline candidates with sickle cell trait since it may associate with kidney disease.
Aim of the study:
To evaluate the immediate and long-term outcomes of a small case series of 17 live kidney donors with sickle cell trait compared to propensity score matched donor controls without sickle cell trait (SCT).
Methods:
Records from the RELIVE study which included 8922 living kidney donors from the University of Minnesota, the Mayo Clinic-Rochester, and the University of Alabama Birmingham. Donations took place between 1963 and 2007.
Donors were contacted in 2010–2012 by mail requesting participation in the RELIVE Study.
None of the participating centers accepted donors with sickle cell disease, and it is unclear how many donors were actually screened for SCT or why those with SCT were screened.
Post-donation hypertension, CV disease, proteinuria, and GFR were assessed.
Results:
The prevalence of SCT in African American donors was 11 per 1000 compared to 73 per 1000 in non-donor AA.
Donors with SCT were younger than the controls.
Nine were AA, six were White, and two were listed as other or unknown ethnicities.
After a follow-up period of 18.2 ± 10.5 years, the proportions of donors with SCT and controls who were alive and developed hypertension or cardiovascular disease were similar.
No donor with SCT developed an eGFR <30 mL/min or kidney failure.
SCT was associated with an increased risk of proteinuria.
Conclusion:
Patients with SCT who donate their kidneys did well but developed proteinuria, which could be an early sign of renal disease. More data is needed.
Limitation:
Level 3
Thank You
See my comments above
Please summarise this article in your own words
INTRODUCTION
AA are at high risk of ESKD. Those with APOL1 high-risk gene polymorphism (11-13%) and SCT (8-9%) are more likely to develop ESKD. Screening of SCT not done despite identical percentage of APOL1 gene
KEY WORDS: sickle cell trait (SCT), African-Americans (AA)
)
AIM OF THE STUDY
Address immediate and long-term outcomes of live donor SCT compared to matched donors without SCT
MATERIALS AND METHODS
They used data from the Renal and Lung Living Donor Evaluation (RELIVE) Study. RELIVE included 8922 living kidney donors (1963 and 2007). Seventeen SCT were matched with 68 donors with no SCT (1:4). Donors were asked if they developed DM, HTN, kidney disease, CVD, cancer, and other conditions and also for quality of life
RESULTS
For the 17 donors with SCT: nine are AA, six are White, and two listed as other or unknown ethnicity. Of the nine AA donors with SCT, eight donated to related AA recipients, 5/6 White donors donated to related White recipients
After a follow-up of 18.2±10.5years, one donor with SCT (5.9%) died, two (11.8%) developed CVD, five (29.4%) developed HTN, and five (31.3%) reached an eGFR<60mL/min. None of the donors with SCT developed an eGFR<30mL/min or ESKD. Outcomes were similar of donor controls with the exception of proteinuria as four (28.6%) SCT donors developed it compared to three (5%) in controls
LIMITATIONS
*Small size
*Lack of information on how the diagnosis of SCT was ascertained and how many donors were actually tested for SCT
CONCLUSTIONS
Donors with SCT were doing well with the exception of increased proteinuria which is an early sign of kidney disease. Risks of reduced eGFR, HTN, and CV disease were the same and. Excluding SCT from donation therefore should be revised particularly in older donors
AA donors should be screened for SCT as for APOL1 gene for more studies of proteinuria
What is the level of evidence provided by this article?
Level 3
Thank You
I agree; level 3, case-control/retrospective study