Thank you All I ready enjoyed your critical appraisal. I can clearly see a dramatic improvement. I intentionally put this paper and the other one in the next journal club to realise the difference in design and how this difference can give different results which is sometimes misleading.
My question: If you have the chance to design a similar study, outline briefly (please briefly) how would you correct the weaknesses you kidney mentioned?
This a retrospective case control observational study which had low evidence level
so if l had the chance to design a similar study I will did it for larger Number prospectively with valid investigations tools in follow up of donor risk factors for longer time :
1-like ambulatory blood pressure measurement
2-Albuminuria measurement
3-GFR measurement
4-screening for diabetes
Prospective design multi-centers different ethnicity, and better international collaboration to get large sample size from different nations and matched to nondonor healthier group to avoid selection bias.
The controls group should be well-matched by demographic and clinical characteristics
Standardized the GFR measurement at the time of enrollment and upon FU for both groups.
reduce the selection and statistical bias by manual or electronic data collection and avoid self-reporting or surveys.
Target long Follow up
I would do randomized controlled trial with three arms as follow:
Donors whom received kidney.
Potential donors fully evaluated.
General population.
All with comparable age group and demographics, including comorbidities(obesity, smoking, DM, prediabetes,HTN, dyslipidemia, GFR, drugs …etc
The donors and the potential donors underwent the same protocol of evaluation.
*Increase the numbers of patients with ideal data collection to avoid the response and survival bias.
*Increase the numbers of study area.
*White and non white donor should be involved in the study.
*The selection of ideal control group should be according to healthy potential donors not according to the general populations.
*Measurement of the GFR, proteinuria, HTN for long period and with recent diagnostic methods
1-Enlarge the sample size;
Help to estimate the incidence of a relatively rare event and to make inferences specific to race/ethnicity subgroups, providing critical information not only for those considering donation .
2-Use an ideal control group;
The comparison with a healthy non donor cohort matched on a wide range of demographic and clinical variables.
3- View more relevant current studies that, have examined renal function in kidney donors.
people: include different races, ethnic groups, and multiceneters.
include optimum and suboptimal donors intervention: study survival and risks for ESRD i.e. HTN, albuminuria, GRF by creatinine clearance, then translate them into a standardized calculated accurate estimate comparison compare with screened healthy nondonors
Time: longer duration for follow up
A study comparing outcomes in renal donors should be:
1) A multi-center study with large number of cases and controls.
2) With healthy, potential donors as controls, who should be matched to the donors with respect to age, gender, race/ ethnicity, hypertension, BMI etc.
3) Proper randomization
4) A prospective study with long-term follow-up (More than 20 years at least)
5) Robust data keeping involving testing and examination of the subjects (instead of phone interviews and self-reportage) with ultimate goal of evaluating endpoints like fall in GFR, ESRD, death, development of hypertension, diabetes etc.
I will include a very large number of donors from different centers.
I will include control groups by similar potential donors who didn’t donate.
I will follow them over a very long period of time.
I will classify all donors and control groups to certain subgroups according to their demographic data, medical histories, laboratory panels, … etc, then to manage separate results with the subgroups, searching for possible risk factors for the adverse outcome of donation.
If I would have to design similar study, I would like to do following:
1. Prospective and multicentric study to include different racial groups
2. Long-term Follow-up
3. Will include non-Donors with similar characteristics as Donor, meaning an ideal matched control
4. Active monitoring of kidney functions with KFTs, Urine Spot Albumin Creatinine ratio/24 hours Urinary proteins as a protocol like donors in control group as per schedule
– larger number of cases.
-control group should be matched in age ,sex ,race , carefully selected to be eligible for donation.
-Long follow-up period up to 20 years .
– retrospective study with proper collection of dara from multi-center.
-dara collection by health reports not self report
The design I would consider is to compare the cohort of patients characteristics to an equivalent control group {age, sex, race and other risk factors },This group is preferably consist of potential donors because the general population control is featuring heterogenous characteristics .that might overshadow the outcome of the study. And overestimate the study findings.
· If I want to choose a study design, I would like to have prospective study, large and multicenter one.
· choose controls as those who were screened for donation, but did not donate, and well matched with the study group/ not from the general population. In addition, standardization of measurement methods of proteinuria and GFR.
· 24 h urine creatinine clearance is the best method to assess the GFR (rather than e GFR)
1-multi-Centre study sample
2-More donors group for study
3-Long time follow up
4-Ideal control group
5-Data collection not from persons only
6-Use more resent tolls to estimate GFR and kidney function
7-I should consider all other risk factors for ESKD
if conduct similar study
1- large sample size
2- use standard measurement for proteinuria and GFR by 24 hour urinary collection
3- randomized control trial more beneficial.
4- control group is better to be healthy donors than general population.
If you have the chance to design a similar study, outline briefly (please briefly) how would you correct the weaknesses your kidney mentioned?
I would design a prospective study comparing long term kidney outcome of donor vs healthy individual. It will be comparing eGFR, UACR, post-transplant blood pressure, post transplantation diabetes and patient survival.
The study will be conducted at multicentre involving multiple race- in our country (Malaysia) it can be multiracial involving – Indian, Chinese, and Malay. Other centres involving Caucasian, Hispanics and Africans will added to make the study more relevant to all races.
eGFR will be measured using CKD EPI with cystatin C which will measured pre donation, at 1 year, 3 years and 5 years.
Wee Leng Gan
2 years ago
small sample size.
response and survival bias.
lack of generalizability of the results due to racial bias.
The use of the MDRD study equation to estimate the GFR for the comparison of current and baseline rates is limited by the fact that this formula was developed in people with a GFR of less than 60 ml per minute per 1.73 m2, and the usefulness of the equation above this level is limited.
Serum creatinine was calibrated at the time of measurement of the iohexol GFR but not at the time of donation, a factor that may have resulted in imprecise estimates of the change in the estimated GFR after donation.
Lack of an ideal control group.
Rehab Fahmy
2 years ago
Because of small sample size,sngle center ,not double blinded ,they considered general population as control group ,very short follow up period .they neglected race as a risk factor .using MDRD formula in GFR calculation To correct it I will reverse these weak points
Wadia Elhardallo
2 years ago
This study was conducted to assess the long term consequence of donation: namely survival risk of end-stage renal disease (ESRD) by measured the glomerular filtration rate (GFR) and urinary albumin excretion and assessed the prevalence of hypertension, general health status, and quality of life.
Ø The main Drawback is that donors were compared to general population: The most important limitation of this study is the lack of an ideal control group.
Ø The glomerular filtration rate (GFR) and urinary albumin excretion
and assessed the prevalence of hypertension, general health status, and quality of life in 255 donors only.
Ø Study on donors who were known to be alive.
Amna Khalifa
2 years ago
The control group is not valid for comparison
The study population were small
Has a survival Biases
Same ethnicity
GFR is estimated rather than measured using a formula developed in people with a gfr of less than 60ml/minper 1.73m2.
Amna Khalifa
2 years ago
the conclusion of this study is not valid as ,
Age of the donors as the study period from 1963 through 2007
Selected populations were all white (same race, so cant apply to all).
Used old calculations of GFR.
The control group were healthy population.
Mohamed Ghanem
2 years ago
The result of this study is no more valid, will you explain why?
size of the sample : small
survival Biases
Because the majority of live donors were white, the results’ external validity was reduced.
Calculating GFR using the MDRD equation
There is no perfect control group
Theepa Mariamutu
2 years ago
Long-Term Consequences of Kidney Donation
The result of this study is no more valid, will you explain why?
The retrospective study is done a single centre at University of Minnesota, no healthy cohort to compare with – this study should have done prospective study comparing with heathy individual 1:1 or 1:2
The recruitment is from 1963 to 2007- where the surgical advances might differ from 1963 to 2007 which might give differences in outcome
consulted telephone and internet directories and asked recipients for their specific donor’s contact information- this method of retrieving information will lead to recall bias
Study population mainly form white population- it may not represent other races
eGFR calculated by MDRD which no more accurate in patient who had eGFR more than 60- the specificity and sensitivity of the method is questionable
Comparing eGFR measured by MDRD then with iohexol GFR – paired T test will be inaccurate with differences of measuring techniques.
Ahmed Omran
2 years ago
The conclusions of this study are no longer valid; because:
A small number of donors, risks compared to general population ,the analysis has response and survival bias and only white donors were included in the study. Additionally, due to the use of the MDRD equation for GER estimation ,serum creatinine was calibrated when measuring iohexol GFR but not at the time of donation which resulted in post donation imprecise estimate of GFR change and lack of standard control group.
Abdullah hindawy
2 years ago
The result of this study is no more valid, will you explain why?
There are multiple limitationn for this study :
1- the most important thing is the controll groub (general population ).
This is not un ideal controll groub .
2-small size study
3-Just still living donors without deadly donors
3-Most of the patients are from the same ethinicty (white)
4-lack of informatient from huge number of patients
5-The way GFR was calculated and the way to determin kidney injury .
how would you correct the weaknesses you kidney mentioned?
1-By increasing the number of patient and expand to all transplant centers
2-Choose the ideal controll groub
3-use accurate method to detect kidney disease .
4-Increase the duration of follow up
Last edited 2 years ago by Abdullah hindawy
Ahmed Abd El Razek
2 years ago
The result of the study is no longer valid, as the control group is the general population which is not totally healthy compared to clinically fit healthy renal donors, they are subjected to the burden of variable comorbidities including ESRD itself.
This study was limited regarding the number of renal donors included, also the ethnicity was almost the same as well as white donors were only considered.
Assessment of renal functions by serum creatinine compared to eGFR was performed late not at time of donation.
The study time is relatively short compared to other studies which extended more than 15 to 20 years.
Abdullah Raoof
2 years ago
The weakness of this study are
1- Retrospective study.
2- Single center study.
3- There is a bias in selection of control group and bias in comparison.
4- There is a problem with data collection.
5- Indicate no negative consequences of donation which is refuted by later on studies.
6- Small sample size and there is ethnicity bias ( white).
7- Using the estimated but not measured GFR.
TO CORRECT THIS STUDY IT IS BETTER TO DO
1- Large size sample, multicenter study .
2- Well-designed sex and age matched study group (patient and control group)
3- Adequate duration of study.
4- To use the measured instead of estimated GFR.
5- To use prospective other than retrospective study.
Hamdy Hegazy
2 years ago
The result of this study is no more valid, will you explain why?
Limitations of this study:
1-small sample size.
2-short follow up duration.
3-Racial Bias because of including predominantly whites.
4-Response and Survival Bias.
5-e-GFR by MDRD study equation.
6-absent control group.
7-High attrition rate.
Ahmed Fouad Omar
2 years ago
This study showed that kidney donors have a similar life span and risk for ESRD compared to the general population:
The results are no more valid as:
The control group is general population. Better design if kidney donors ( were carefully selected after medical screening for any medical condition) to be compared to eligible donors who were fit for donation but didn’t donate
Donor number is small and only white donors were included in the study, so the results could not be generalized
The use of MDRD equation to estimate GFR is also a limitation. It is not suitable for use in patients with GFR >60.
Serum creatinine was calibrated at the time of measurement of GFR but not at the time of donation.
The analysis is subjected to response(those with available contact details) and survival bias.
The duration of the study despite being long, but there are more longer studies with follow up that extended beyond 20 years and showed different results (donors do have an increased risk of ESRD).
A better design:
Use healthy donors rather than general population as the controls
Include different ethnic groups
Better to be a prospective multicenter design with larger number of donors
Electronic data collection and avoid self-reporting.
Standardize the GFR measurement at the time of enrollment and follow up
Longer duration of follow-up
Hinda Hassan
2 years ago
This study was one of basis of the myth that kidney donor have a life span and health status that is similar to that of the general population.
The drawbacks of this study are:
1- It is an observational comparative study
2- The sample technique is through stratified sampling which despite being considered a type of random sampling; it is affected by response bias. bias as the donors who can be reached out are the one who are included. I think this sampling is more like quota which is non-random sampling
3- Small number of donors only 255 is included despite the large number of kidney nephrectomies (3698) which was done throughout the study period. This made the sample unrepresentative of this population.
4- The controls were only matched for few criteria without considering other confounding which might be present.
5- There are a number of donors who died so there was survival bias. . They need to be added in the analysis (NNT). The cause of death was unknown for 162 donors
6- Most of the donors are white so the result of this study cannot be generalized.
7- The use of the MDRD study equation at the time of donation to estimate the GFR was another major drawback. It is designed for GFR that are less than 60 ml per minute per 1.73 m2. This was compared with a measured creatinine later on.so the estimation of GFR changes over the study period is not accurate.
Manal Malik
2 years ago
The result of this study is no more valid, will you explain why? 1-this study is invalid as there are recent studies concluded that kidney donors have a sighnificant increased risk of ESRD.
2-the control group is general population but idealy should be living donors.
3-study group population included only white people .
4- sample size is small so if we need to make it larger study to be multicentre.
5-GFR is calculted so idealy to be measured rathe than calculation
6-serum creatinine measure at the time of eGFR idealy should be at time of donation
Amna Khalifa
2 years ago
the results is not valid because of
The control group is not valid for comparison
The study population were small
Has a survival Biases
Same ethnicity
GFR is estimated rather than measured using a formula developed in people with a gfr of less than 60ml/min per 1.73m2.
i would design a study , multicentre , using controls age and sex match, will follow them for longer duration and measure properly renal function and any factor which can attribute to the patient survival.
rindhabibgmail-com
2 years ago
Because it needed more data to decrease bias.
It should be multicentrac, RCT, proper randomization, needed proper and ling term follow-ups.
Filipe Prohaska Batista
2 years ago
It is a retrospective study with single center data from November 1963 to December 2007 with 3698 nephrectomies in living donors excluding patients with arterial hypertension, diabetes mellitus, and proteinuria. Although 80% of the donors were contacted, only 255 underwent the necessary new tests. Comparison with the general population becomes a major problem, due to different characteristics, after all, the first group is selected from a select group of donors compared to a predominantly obese population with metabolic alterations.
For donors who died, there is no robust data on how it happened, being restricted to comments from family members or data in the system coded by disease. Follow-up data were also restricted to periods close to 5 to 7 years, which may mask the complications resulting from transplants with longer periods.
The conclusion of this study indicates that kidney donors have a good quality of life and performance status similar to the general population, giving a false impression that nephrectomy has no consequences. Subsequent studies comparing an audience with similar characteristics for a longer follow-up period showed discrepant data.
Alyaa Ali
2 years ago
The results of study are Invalid. As the study had many limitations
1. Small sample size
2. There is response and survival bias , only donors with available contact data or who still alive were included.
3. Most of living donors were white , this limited the generalization of results, as 14% of living donors in US are non-white
4. Using of the MDRD equation for estimation of GFR, as this formula was developed to estimate GFR less than 60 ml per minute per 1.73 m2
5. Serum creatinine was calibrated at time of study but not the time of donation
6. Lack of ideal control group
To correct weakness
1. Larger sample size
2. Ideal control group who are well matched to donors
3. Measurement of GFR rather than estimate it
4. Do multicentre studies
Mu'taz Saleh
2 years ago
The result of this study is no more valid, will you explain why?
1- control group : potential donor is one who is healthy with no medical problem and will investigated so its not correct to compare the potential donor with general population 2-2- number of donors are small and from same medical center
3- Most of the living donors were white
4- using MDRD instead of CKD EPI in calculating eGFR
thanks
Jamila Elamouri
2 years ago
Long-term consequences of kidney donation: Limitations:
1- Small size of the sample, so represent the proportion of all donors
2- The study includes only donors with available contact information who are still alive, this causes the study to be subject to both response and survival bias.
3- The majority of the donors are white, limiting the generalization of the results, although; the nonwhite donors represent only 14% in the USA.
4- The MDRD equation was developed in people with GFR < 60 ml/min/1.73 m2 and its usefulness above this level are limited. So, its use in this study adds limitations to it.
5- S. Cr was measured as well, at the time of iohexol GFR measurement, but not at the time of donation, this may result in a vague estimate of the change in the estimated GFR after donation.
6- Lack of an ideal control group. As it uses the general population for comparison, it was better to use sibling controls who were screened for donation
by these limitation the study result can not be generalized.
If I design a study I will suggest to be:
1- a prospective study over a long period
2- a large sample
3- multi centres
4- ideal control group (sibling whom did not donate but subject to evaluation during search for donor)
5- same equation for GFR estimation a donation and during the study (24h urine creatinine clearance)
6- good match of the donor and control
7- do not include dead donor with lack of information
Hussam Juda
2 years ago
1- More recent studies andBTS/RA Living Donor Kidney Transplantation Guidelines 2018, indicates that risk of ESKD increased by donation
2- This study has many limitations, which make it weak study and unreliable:
Matched group is general population which is not ideal
All risk factors should be compared like smoking, obesity, race, HTN, DM, and age
We need bigger group for study
We need longer duration for follow up as ESRD may need a longer time to occur
Recently CKD-EPI formula should be used to estimate GFR
Most of donors of the study were white, so the results could be no applicable on non-white.
Information was given by alive donors only, which indicates bias in response and survival
mai shawky
2 years ago
The current article is not valid.
· The current study founded that, the long term outcomes of donors is similar to those who were none donors as regard the decline in GFR and albuminuria.
· proteinuria was assessed as morning sample spot urine for ACR, GFR as clearance of nonradioactive iohexol and hypertension when ABP was >140/90 or need of antihypertensive medications.
· Similar mortality rates to non-donors, 1/3 mortality was due to cardiovascular mortality.
· ESKD developed in donors (related living donors with the same original kidney disease of the recipients), but similar rate to that of general population.
· This can be attributed to wide scale screening for health problems in donors.
· The current study findings cannot be validated due to the following point of weakness:
o absence of similar control group, and the comparison with general population.
o an old study involved previous studies before 2009.
o Small sample size (although 3698 donors had been assessed, but only 1 of 7 donors responded.
o Relatively insufficient period for follow up,
o use of e GFR by MDRD equation which is not valid in GFR > 60 ml/min/m2.
Wael Jebur
2 years ago
In order to assess the long term outcome of kidney donation , a study was conducted to include donors from 1963 through 2003 with median follow up period of 15 years post donation in. 3698 donation nephrectomies were performed in Minnesota university hospital. From 2003 through 2007 , 255 donors were evaluated for proteinuria and eGFR, blood pressure was done to evaluate for underlying hypertension.
Results of the study revealed 11 ESKD patients, with varied etiology ,ranging from Diabetic nephropathy, hypertension, interstitial nephropathy and glomerular disease.
The control group was selected from NHANES.
The outcome of the study showcased a comparable results to the control group, indicating that the life span , risk of ESKD, proteinuria and hypertension incidence in donors was similar to its incidence in general population..
The main cavate of the study was the control group . as it was heterogenous and non matching the study cohort…
Maksuda Begum
2 years ago
This study indicates that kidney donors have a normal life span, a health status that is similar to that of the general population, and an excellent quality of life; they do not have an excessive risk of ESRD.
Questions challenging the validity of this study?
They don’t have an ideal control group, donors were matched with General population.
This study is not valid as there are many limitations of this study which are mentioned in the limitation section.
The better way of doing this study would be:
Prospective (this will minimize the recall bias)
Multicentric
Controls should be from the same population who are healthy enough to be potential donors matched for age, sex and most important ethnicity
Measurement of GFR using 24 hours urine creatinine clearance at the time of enrollment and at regular follow-up would be ideal
Creation of National level Donor registry would be ideal for such long-term studies.
Shereen Yousef
2 years ago
The result of this study is no more valid, will you explain why?
-The small sample size which will affect the results .
– Single center study, not double blind may influence the results.
– consideting general population as control group without beeing matched in health status to donors which is fully investigated and carefully selected.
-very short follow-up period to evaluate long termeffect.
–effect of of race was neglected as all participants were white while higher risk if kidney disease is will known risk factor in African-Americans.
– using eGFR by MDRD rather than measured GFR ,also its not the best equation for healthy population .
– collecting dara through phone contact and contacting only donors who were known to be alive will affect the results greatly.
Last edited 2 years ago by Shereen Yousef
Rahul Yadav rahulyadavdr@gmail.com
2 years ago
The result of this study is no more valid, will you explain why?
1. Study included small number of subjects
2. Donors were contacted who were alive (in 1:7 ratio) so survival and response bias.
3. Subjects and controls are from one ethnicity i.e. whites, so similar conclusions can’t be extended to other ethnicities or to general population
4. Use of MDRD equation for estimation of GFR to compare current and baseline kidney function
5. Control group in matched in terms of age, sex and race and not an ideal control group having characteristic’s similar to a donor (like lack of comorbidities)
Mohamad Habli
2 years ago
The results of this study is in favor of living kidney donation with excellent long term outcomes for the donors as results of the study include:
Comparable donor survival with general population.
ESRD incidence is similar to general population.
Stable GFR in the follow-up.
Incidence of albuminuria and hypertension was comparable between donors and general population.
In contrast to the results of this study, same author has conducted studies on the long-term effects of donation from donors with different risk factors and the results came out with higher risk comparing to the control groups.
The results of the study could be no more valid because of selecting general population (with different risk factors) as a control group along with bias, in addition to including patients since 1963 with possible inadequate followup or evaluation/documentation in the post donation period.
Mohammed Sobair
2 years ago
The result of this study is no more valid, will you explain why?
The lack of an ideal control group.
a small numbers of donor studied.
Its retrospective study.
Includes only white donors.
GFR not estimated.
Selection bias ,only those who have contact.
Cause of death in those who died not identified .
The use of the MDRD study equation to estimate the GFR.
Sahar elkharraz
2 years ago
Long Term Consequences of Kidney Donation:
This article address risk of ESRD in living donor from 1963 to 2007, where efforts start from 2003 to 2007 in university of minnesota.
The most of living donor has quality of life better than general population.
Life expectancy appear similar to non donor and there’s no risk of ESRD or raised creatinine level even more than 30 years post donation.
Criteria of selection donor:
Free of DM and hypertension
GFR > 80 ml/min / 1.73m2 of body surface area
They provided good history and examination
Renal and vascular imaging
Laboratory studies to role out liver disease/ active infection and systemic illness
Urinary albumin creatinine ratio > 0.02 in one occasion was accepted.
All donor with albuminuria excluded from donation
In December 2003 do comprehensive efforts to contact all persons who donated kidney transplant after november 1963. Around 80% of donor was accepted to contact. They were full information regarding health status and asked for urine routine and creatinine level/ blood pressure measurements 3 times while donor seated.
All patients with blood pressure more than 140/90 considered hypertension or use anti hypertension medication.
Quality of life assessed by medical outcomes studies focus on general health survey.
Expected mortality rate was measured in comparison to general population.
Risk of ESRD in general population was calculated from 2007 by Annual data reports of united states renal data system.
Survival rate and ESRD expected post donation was similar to general population.
General health assessed by age at time of donation/ Bp measurements/ BMI and smoking/ baseline eGFR by used of MDRD equations.
Mortality rate in donor was 30% related to cardiovascular disease not from ESRD.
Low risk of ESRD seen in donor and related to hypertension and DM and few from glomerulonephritis especially in those donate to their siblings.
In this survey no donor who died had needing to dialysis or transplant.
The estimated incidence of ESRD in donor appear to be 180 per million persons per year as compared to 268 per million persons annually.
Mean creatinine level at time of donation 0.9 and eGFR 84 ml / min. mean of creatinine level after donation 1.1 & GFR 63 ml/min.
The young age at time of donation the longer time since donation and high eGFR and greater compensation but high protein creatinine excretion ratio.
The average hypertension is 122/70. Those with high blood pressure has high risk of cardiovascular disease. The risk of proteinuria associated with old age donor and high BMI.
Decline of eGFR not associated with smoking donor. However more in diabetic patients and hypertension patients.
Quality of life is excellent in donor and it’s may related to carful selected of donor in comparison to general population. Donors less likely to be smoking and less like to develop cancer.
There’s no significant difference between donor and non donor in prevalence of hypertension and DM.
Limitations of this study is small group and lack of informative data .
In conclusion, They concluded that kidney donors have a normal life span.
Good a health status similar to the general population
An excellent quality of life
No risk of ESRD because carefully selected
The rates of albuminuria and hypertension were similar to those of matched controls.
Dalia Ali
2 years ago
Limitations
1-the study included only a small, though representative, proportion of all kidney donors to date.
2-Only donors with available contact information who are still alive participated in this effort
3-Most of our living donors are white, a factor that may also limit the generalizability of our results, though only 14% of living kidney donors in the United States are nonwhite.
4-The most important limitation of our study is
the lack of an ideal control group.
The data offer prospective donors information regarding their life span and their risk of ESRD as compared with those of the general population, but it would be even more informative to compare their outcomes with those of sibling controls who were screened for donation and accepted as donors but did not donate a kidney, since kidney donors are carefully screened and are healthier, on average, than general-population controls.
Conclusion
1-The study indicates that kidney
donors have a normal life span
2-a health status that is similar to that of the general population, and an excellent quality of life
3-they do not have an excessive risk of ESRD.
The majority of donors in this study had a preserved GFR, and their rates of albuminuria and hypertension were similar to those of matched controls.
fakhriya Alalawi
2 years ago
· Being a retrospective analysis carries much bias
· The study had included 80% of the donors, not all as many had died.
· The control group included the general population based on Human Mortality Database, which combines data regarding survival and death rates from the National Center for Health Statistics with data from other sources, which means the included general population have many comorbidities. Similarly, the rate of ESRD in the general population was obtained from the 2007 annual data report of the United States Renal Data System.
· It should include donors from multicentric trials
Ibrahim Omar
2 years ago
The result of this study is no more valid, will you explain why?
the results are not valid due to several limitations including the following :
1- the study included a small fraction of all kidney donors (1 out of 7 donors). the included donors were only those who are still alive and whose contact numbers were available.
2- most of the included donors were white that limits the generalization of the results of the study.
3- the use of MDRD study equation for eGFR as this equation was developed for people with GFR less than 60 ml/min.
4- serum creatinine was calibrated at the time of measuring GFR but not at the time of donation. therefore, there were imprecise estimates of changes in GFR post-donation.
5- lack of ideal control groups. the study included general populations as control groups. it was better to use sibling controls who were screened for donation and accepted as donors but they didn’t donate. these potential donors are presumed to be more healthier to the general population.
several high powered studies including ideal control groups revealed opposite results.
Amit Sharma
2 years ago
· The result of this study is no more valid, will you explain why? The study is not valid in view of certain limitations: 1) There is lack of an ideal control group: the study used general population as controls, who would be less healthy than the study population (donors) selected after intense evaluation. 2) The sample size was small 3) The follow-up was of short duration. 4) The study population included predominantly whites, hence racial bias present 5) The study had response and survival bias 6) The GFR was calculated using MDRD study equation 7) There was high attrition rate 8) Most importantly, another study published later-on did compare outcomes of donors with healthy non-donors, invalidating the findings of this study by overcoming a major limitation.
Mahmud Islam
2 years ago
The excellent optimistic results showed close similarity in survival between donating and non-donating people, which was shown to be inaccurate in later papers. Limitations of the study like relatively smaller number compared to other studies and dependence on already available data limited by the availability of contacts as reported by the writers. Accordingly, both response and survival bias are considered. Ioxehol clearance is not a standard or practical nowadays.
This study can be redesigned as a randomized trial. only 255 donors underwent measurement of the GFR. This is not representative.
Huda Saadeddin
2 years ago
This study indicates that kidney donors have a normal life span and an excellent quality of life; they do not have an excessive risk of ESRD with preservation of GFR
but certain limitations in this study which are listed below
The most important limitation of this study is the lack of an ideal control group.
The study included only a small number of all kidney donors to date.
The analysis is subject to both response and survival bias.
Most of the living donors sharing the study are white, a factor that may also limit the generalizability of the study results.
The use of the MDRD study equation to estimate the GFR for the comparison of current and baseline rates is limited by the fact that this formula was developed in people with a GFR of less than 60 ml per minute per 1.73 m2 , and the usefulness of the equation above this level is limited.
Serum creatinine was calibrated at the time of measurement of the iohexol GFR but not at the time of donation.
That is a good use of bold type for the sake of emphasis, dear Dr Rihab.
Alaa eddin salamah
2 years ago
The result of this study is no more valid, will you explain why?
Only a small number of kidney donors to date were included in the study. Only donors who could be reached and who were still alive contributed to this project (a rate of one of seven selected donors). As a result, both response bias and survival bias can affect our analysis. Although just 14% of live kidney donors in the United States are nonwhite, the majority of our living donors are white, which may also restrict the generalizability of our findings.
The MDRD study equation was established in patients with a GFR of less than 60 ml per minute per 1.73 m2, and the utility of the equation above this level is limited. As a result, the use of the equation to estimate GFR for the comparison of current and baseline rates is limited.
Inaccurate estimates of the change in the estimated GFR after donation may have been caused by the fact that serum creatinine was calibrated at the time of measuring the iohexol GFR but not at the time of donation.
The absence of an optimal control group is our study’s most significant shortcoming. Our data provide prospective donors with information on their lifespan and risk of ESRD in comparison to that of the general population, but it would be even more insightful to compare their outcomes with sibling controls who were screened for donation and accepted as donors but did not donate a kidney because kidney donors are rigorously screened and, on average, healthier than general population controls.
The result of this study is no more valid, will you explain why?
– The study indicates that kidney donors have a normal life span, a health status
that is similar to that of the general population, and an excellent quality of life; they do not have an excessive risk of ESRD. The result of this study is no more valid because :
1.The study included only a small, though representative, proportion of all kidney donors to date and only donors with available contact information
who are still alive participated in this effort .
2.Analysis is subject to both response and survival bias.
3.The lack of an ideal control group.
4.Most of living donors are white, a factor that may limit the generalizability of results .
5.The use of the MDRD study equation to estimate the GFR which was developed in people with a GFR of less than 60 ml per minute per 1.73 m2, and the usefulness of the equation above this level is limited.
6.Serum creatinine was calibrated at the time of measurement of the iohexol GFR but not at the time of donation, a factor that may have resulted in imprecise estimates of the change in the estimated GFR after donation.
This study had limitations. First of all, selection bias by selecting a small percent of all donors and only those who were alive or had contact information were studied.
Most donors were white that increase selection bias. In addition, using MDRD equation for evaluating GFR was not appropriate. GFR measurement by iohexol was only done in a low present of donors’ post-donation and not before donation that limit comparison of GFR before and after donation.
Control group was not ideal, too. Using sibling controls would be better. Multi-central study with large number of donors will be more informative.
The result of this study is no more valid, will you explain why? The study design had many limitations: People: include reactively small numbers, white only, single-center and optimum donors. Intervention: depended on recalls for the recipients about their donors’ information, no solid data about all donors and their follow up including dead donors and those who were unable to connect with them. Comparison: with the general population whatever their comorbidities and their risks for ESRD Outcome: many outcomes were searched i.e. (survival, proteinuria, HTN, quality of life ) and were not looked for in all participants Time: short time period for follow up
That is a list of good suggestions. Dr Patil, especially a national level donor registry.
Last edited 2 years ago by Ajay Kumar Sharma
Muntasir Mohammed
2 years ago
This study is no more valid for many reasons:
1-The control group is not like study group, donor. This is because donors were highly selected, healthier, and followed up not like general population, some of whom may have undiagnosed medical problems.
2-Donation period was relatively older 1963 to 2007 at time where investigation and surgery may be different from current practice.
3-Follow up after donation is shorter for healthy donors to show effect on the kidney or cardiovascular disease.
4-Number of donors is relatively small.
5-Most of donors are white.
Nandita Sugumar
2 years ago
This study is not valid because :
Controls used were not of similar health to donors – controls also need to be eligible to donate in order to make correct reference
The study results mention that ESRD risk is not increased in kidney donors. This is not true, and recent studies have confirmed that kidney donors have a significantly increased risk of ESRD in their lifetime.
Donors used in this study had to be free from diabetes and hypertension. In the present age, it is very difficult to find such a donor. Even if the donor does not have diabetes currently, they may be at pre-diabetic stage or with family history of diabetes or hypertension. This makes it difficult to apply the results of this study to donors used nowadays.
SPSS statistical software is more accurate compared to SAS software used in the given study
Iohexol for GFR
Ethnic variety of donors in this study is highly limited, with majority being white. This severely impairs application of this study to real life donors since ethnicity can bring about a major change in expected long term consequences in kidney donors.
That is a good analysis, Dr Nandita.
However, I could not understand why use of statistical software influence the interpretation.
Eusha Ansary
2 years ago
Don’t have an ideal control group. The study included only a small number of donors in single center. Only donors with available contact information who are still alive participated in this effort. Therefore, the analysis is subject to both response and survival bias.
The use of the MDRD study equation to estimate the GFR is limited by the fact that this formula was developed in people with a GFR of less than 60 ml/minute/1.73 m2, and the usefulness of the equation above this level is questionable.
Majority of donors were white so the result might not hold true for other races. In addition to that, average age of general population is different in different parts of world which can impact these results.
Dear Dr Eusha,
I agree with limitation ‘the lack of ideal control group’, in this paper that you describe.
Last edited 2 years ago by Ajay Kumar Sharma
amiri elaf
2 years ago
# The result of this study is no more valid, will you explain why?
*The study included only a small number of donors in single center. Only donors with available contact information who are still alive participated in this effort (a rate of one of seven selected donors). Therefore, the analysis is subject to both response and survival bias
*Excluding donors who were foreign nationals, the survival of donors appeared to be similar to that of the controls in the general population, but survival could not be formally compared, since life tables from the National Center for Health Statistics do not provide confidence intervals for the probability of survival in the general population.
* Most of the living donors are white that limit the result, a factor that may also limit the generalizability of the results.
*The use of the MDRD study equation to estimate the GFR for the comparison of current and baseline rates, which is not suitable for the GFR less than 60 ml per minute per 1.73 m2.
*Serum creatinine was calibrated at the time of measurement of the iohexol GFR but not at the time of donation a factor that may have resulted in imprecise estimates of the change in the estimated GFR after donation. .
*The lack of an ideal control group, data offer prospective donors information regarding their life span and their risk of ESRD as compared with those of the general population, but it would be even more informative to compare their outcomes with those of sibling controls who were screened for donation and accepted as donors but did not donate a kidney, since kidney donors are carefully screened and are healthier, on average, than general-population controls.
Dear Dr Elaf,
I agree with limitation of this paper that you describe ‘the lack of ideal control group’.
Batool Butt
2 years ago
This study studied the long term consequences of kidney donation & risk of ESRD in donors & non donor population which revealed that no risk of ESRD on account of albuminuria , preserved GFR & quality of life in comparison to general population .This study is no more valid as it is a single center study with small sample(3698 kidney donors) and results can not be generalized because of white population only. The control group is not ideal as general population is not healthy and also MDRD equation for GFR estimation is considered as validity above GFR 60 ml/min/1.73m2 is limited and creatinine not caliberated at the time of donation. Response and survival bias is present in the study as only alive donors with available contact information were included. Data mainly reported by the donors or recipients themselves.
Dear Dr Butt, I agree with limitations of this paper that you describe biases and ‘the lack of ideal control group’.
Last edited 2 years ago by Ajay Kumar Sharma
Assafi Mohammed
2 years ago
Long-Term Consequences of Kidney Donation
1. The study ascertained the vital status and lifetime risk of ESRD in 3698 kidney donors who donated kidneys during the period from 1963 through 2007 at the University of Minnesota.
2. In a 255 donors, from 2003 through 2007, the study parameters for evaluation were:
a) The measured glomerular filtration rate (GFR) and urinary albumin excretion to overcome the limitation of the previous studies.
b) Prevalence of hypertension.
c) General health status and quality of life. Study’s result and conclusion
1. Survival and risk of ESRD are similar between donors and the general population.
2. Donors had a lower estimated GFR, lower systolic blood pressure, and a lower urinary albumin excretion rate in comparison to the general population.
3. Self-reported diabetes and use of antihypertensive medications were similar in the two groups(donors and non-donors).
4. The life span of kidney donors is similar to that of persons who have not donated a kidney.
The result of this study is no more valid, will you explain why?
1. The confidence intervals for the probability of survival in the general population was not provided by the national center for health, so the survival wasn’t formally compared.
2. The study included only a small proportion of all kidney donors.
3. The analysis is subject to both response and survival bias (a rate of one of seven selected donors).
4. Most of the living donors were white, which may limit the generalizability of the results.
5. The used MDRD formula is not useful when the GFR is > 60( the formula was developed for those with GFR <60).
6. The calibration of SCr to measured GFR using iohexol, wasn’t at the time of donation. This may have resulted in a change in the estimated GFR after donation.
7. The have a lack of an ideal control group(the ideal control group is those who screened as potential donor and didn’t donate).
Dear Dr Assafi Mohammed,
I agree with long list of limitations that you have highlighted in this paper
Zahid Nabi
2 years ago
This study indicates that kidney donors have a normal life span, a health status that is similar to that of the general population, and an excellent quality of life; they do not have an excessive risk of ESRD.
Questions challenging the validity of this study?
They don’t have an ideal control group, donors were matched with General population.
The use of the MDRD study equation to estimate the GFR is limited by the fact that this formula was developed in people with a GFR of less than 60 ml per minute per 1.73 m2, and the usefulness of the equation above this level is limited.
The study analysis is subject to both response
and survival bias.
Majority of donors were white so the result might not hold true for other races, at the same time average age of general population is different in different parts of world which can impact these results.
Dear Dr Nabi, I agree with limitations of this paper that you describe biases and ‘the lack of ideal control group’.
Yashu Saini
2 years ago
This was the study where recruitment of cases was done where donors donated between 1963-2007. So as such in the research world the study is quite old.
But I think the major reason which made study currently invalid is because of taking general population as controls and stating that kidney donors have similar life span like general population with almost same risk of developing ESKD in remaining kidney.
this in current era is almost clear that donors are super selected and they are much more fit than general population so even if we take age, gender, BMI, etc matched controls from general population, the study is erroneous.
Other factors like, single center, small number of cases, self reporting, etc. seem to be the usual limitations which every study has one or the other.
If I consider about tools of analysis, then the researchers used the best available at their time though they have become obsolete or invalid in current era like:
Using MDRD instead of CKD-EPI
Using Iohexol for GFR instead of DTPA
Using SAS software Instead of SPSS for statistical analysis.
Thank you All
I ready enjoyed your critical appraisal. I can clearly see a dramatic improvement. I intentionally put this paper and the other one in the next journal club to realise the difference in design and how this difference can give different results which is sometimes misleading.
My question:
If you have the chance to design a similar study, outline briefly (please briefly) how would you correct the weaknesses you kidney mentioned?
I would do the following changes if I conduct similar study now.
That is a good analysis, Dr Saini.
That is a good analysis, Dr Ben
Thanks prof
This a retrospective case control observational study which had low evidence level
so if l had the chance to design a similar study I will did it for larger Number prospectively with valid investigations tools in follow up of donor risk factors for longer time :
1-like ambulatory blood pressure measurement
2-Albuminuria measurement
3-GFR measurement
4-screening for diabetes
That is a good analysis, Dr Mahmoud.
1.Would try to have ideal control group
2.Would try to have a multi center study conducted in different continents
3.Better to conduct a prospective study.
That is a list of good suggestions. Dr Nabi. .
Prospective design multi-centers different ethnicity, and better international collaboration to get large sample size from different nations and matched to nondonor healthier group to avoid selection bias.
The controls group should be well-matched by demographic and clinical characteristics
Standardized the GFR measurement at the time of enrollment and upon FU for both groups.
reduce the selection and statistical bias by manual or electronic data collection and avoid self-reporting or surveys.
Target long Follow up
That is a good analysis, Dr Mohammed.
That is a good use of bold type for the sake of emphasis, dear Dr Yusuf.
I would do randomized controlled trial with three arms as follow:
All with comparable age group and demographics, including comorbidities(obesity, smoking, DM, prediabetes,HTN, dyslipidemia, GFR, drugs …etc
The donors and the potential donors underwent the same protocol of evaluation.
That is a list of good suggestions. Dr Alshaikh
Sir,
This study is not valid as there are many limitations of this study which are mentioned in the limitation section.
The better way of doing this study would be:
That is a good use of bold type for the sake of emphasis, dear Dr Patil
*Increase the numbers of patients with ideal data collection to avoid the response and survival bias.
*Increase the numbers of study area.
*White and non white donor should be involved in the study.
*The selection of ideal control group should be according to healthy potential donors not according to the general populations.
*Measurement of the GFR, proteinuria, HTN for long period and with recent diagnostic methods
That is a good analysis, Dr Elaf.
1-Enlarge the sample size;
Help to estimate the incidence of a relatively rare event and to make inferences specific to race/ethnicity subgroups, providing critical information not only for those considering donation .
2-Use an ideal control group;
The comparison with a healthy non donor cohort matched on a wide range of demographic and clinical variables.
3- View more relevant current studies that, have examined renal function in kidney donors.
That is a list of good suggestions. Dr Ishag.
people: include different races, ethnic groups, and multiceneters.
include optimum and suboptimal donors
intervention: study survival and risks for ESRD i.e. HTN, albuminuria, GRF by creatinine clearance, then translate them into a standardized calculated accurate estimate
comparison compare with screened healthy nondonors
Time: longer duration for follow up
That is a list of good suggestions. Dr Ellisy
Follow-up of :-
Hi Dr WAdi,
You answer seems to brief for me to understand your thought process
A study comparing outcomes in renal donors should be:
1) A multi-center study with large number of cases and controls.
2) With healthy, potential donors as controls, who should be matched to the donors with respect to age, gender, race/ ethnicity, hypertension, BMI etc.
3) Proper randomization
4) A prospective study with long-term follow-up (More than 20 years at least)
5) Robust data keeping involving testing and examination of the subjects (instead of phone interviews and self-reportage) with ultimate goal of evaluating endpoints like fall in GFR, ESRD, death, development of hypertension, diabetes etc.
lack of an ideal control group REPRESNTIVE control group will be selected.
a small numbers of donor studied Large multicenter study will be more informative.
Its retrospective study prospective long term study and follow up
Includes only white donors .Nonwhite and Hispanic will be included
GFR not estimated. kpi GFR AND scanning more refection of renal function below and
above 6oml/1.73/
Selection bias ,only those who have contact, all or most donors will be included and
cause of death identified
If I would have to design similar study, I would like to do following:
1. Prospective and multicentric study to include different racial groups
2. Long-term Follow-up
3. Will include non-Donors with similar characteristics as Donor, meaning an ideal matched control
4. Active monitoring of kidney functions with KFTs, Urine Spot Albumin Creatinine ratio/24 hours Urinary proteins as a protocol like donors in control group as per schedule
5. Try to cut down Response/Communication bias
Trying to correct all weak points of the study by
– larger number of cases.
-control group should be matched in age ,sex ,race , carefully selected to be eligible for donation.
-Long follow-up period up to 20 years .
– retrospective study with proper collection of dara from multi-center.
-dara collection by health reports not self report
Ideal control group
More sample size
I will measure the GFR rather than to estimate it
If study could be conducted prospectively with proper randomization then this would be the best
The design I would consider is to compare the cohort of patients characteristics to an equivalent control group {age, sex, race and other risk factors },This group is preferably consist of potential donors because the general population control is featuring heterogenous characteristics .that might overshadow the outcome of the study. And overestimate the study findings.
· If I want to choose a study design, I would like to have prospective study, large and multicenter one.
· choose controls as those who were screened for donation, but did not donate, and well matched with the study group/ not from the general population. In addition, standardization of measurement methods of proteinuria and GFR.
· 24 h urine creatinine clearance is the best method to assess the GFR (rather than e GFR)
1-multi-Centre study sample
2-More donors group for study
3-Long time follow up
4-Ideal control group
5-Data collection not from persons only
6-Use more resent tolls to estimate GFR and kidney function
7-I should consider all other risk factors for ESKD
if conduct similar study
1- large sample size
2- use standard measurement for proteinuria and GFR by 24 hour urinary collection
3- randomized control trial more beneficial.
4- control group is better to be healthy donors than general population.
If you have the chance to design a similar study, outline briefly (please briefly) how would you correct the weaknesses your kidney mentioned?
I would design a prospective study comparing long term kidney outcome of donor vs healthy individual. It will be comparing eGFR, UACR, post-transplant blood pressure, post transplantation diabetes and patient survival.
The study will be conducted at multicentre involving multiple race- in our country (Malaysia) it can be multiracial involving – Indian, Chinese, and Malay. Other centres involving Caucasian, Hispanics and Africans will added to make the study more relevant to all races.
eGFR will be measured using CKD EPI with cystatin C which will measured pre donation, at 1 year, 3 years and 5 years.
small sample size.
response and survival bias.
lack of generalizability of the results due to racial bias.
The use of the MDRD study equation to estimate the GFR for the comparison of current and baseline rates is limited by the fact that this formula was developed in people with a GFR of less than 60 ml per minute per 1.73 m2, and the usefulness of the equation above this level is limited.
Serum creatinine was calibrated at the time of measurement of the iohexol GFR but not at the time of donation, a factor that may have resulted in imprecise estimates of the change in the estimated GFR after donation.
Lack of an ideal control group.
Because of small sample size,sngle center ,not double blinded ,they considered general population as control group ,very short follow up period .they neglected race as a risk factor .using MDRD formula in GFR calculation
To correct it I will reverse these weak points
This study was conducted to assess the long term consequence of donation: namely survival risk of end-stage renal disease (ESRD) by measured the glomerular filtration rate (GFR) and urinary albumin excretion and assessed the prevalence of hypertension, general health status, and quality of life.
Ø The main Drawback is that donors were compared to general population: The most important limitation of this study is the lack of an ideal control group.
Ø The glomerular filtration rate (GFR) and urinary albumin excretion
and assessed the prevalence of hypertension, general health status, and quality of life in 255 donors only.
Ø Study on donors who were known to be alive.
The control group is not valid for comparison
The study population were small
Has a survival Biases
Same ethnicity
GFR is estimated rather than measured using a formula developed in people with a gfr of less than 60ml/minper 1.73m2.
the conclusion of this study is not valid as ,
The result of this study is no more valid, will you explain why?
size of the sample : small
survival Biases
Because the majority of live donors were white, the results’ external validity was reduced.
Calculating GFR using the MDRD equation
There is no perfect control group
Long-Term Consequences of Kidney Donation
The result of this study is no more valid, will you explain why?
The conclusions of this study are no longer valid; because:
A small number of donors, risks compared to general population ,the analysis has response and survival bias and only white donors were included in the study. Additionally, due to the use of the MDRD equation for GER estimation ,serum creatinine was calibrated when measuring iohexol GFR but not at the time of donation which resulted in post donation imprecise estimate of GFR change and lack of standard control group.
The result of this study is no more valid, will you explain why?
There are multiple limitationn for this study :
1- the most important thing is the controll groub (general population ).
This is not un ideal controll groub .
2-small size study
3-Just still living donors without deadly donors
3-Most of the patients are from the same ethinicty (white)
4-lack of informatient from huge number of patients
5-The way GFR was calculated and the way to determin kidney injury .
how would you correct the weaknesses you kidney mentioned?
1-By increasing the number of patient and expand to all transplant centers
2-Choose the ideal controll groub
3-use accurate method to detect kidney disease .
4-Increase the duration of follow up
The result of the study is no longer valid, as the control group is the general population which is not totally healthy compared to clinically fit healthy renal donors, they are subjected to the burden of variable comorbidities including ESRD itself.
This study was limited regarding the number of renal donors included, also the ethnicity was almost the same as well as white donors were only considered.
Assessment of renal functions by serum creatinine compared to eGFR was performed late not at time of donation.
The study time is relatively short compared to other studies which extended more than 15 to 20 years.
The weakness of this study are
1- Retrospective study.
2- Single center study.
3- There is a bias in selection of control group and bias in comparison.
4- There is a problem with data collection.
5- Indicate no negative consequences of donation which is refuted by later on studies.
6- Small sample size and there is ethnicity bias ( white).
7- Using the estimated but not measured GFR.
TO CORRECT THIS STUDY IT IS BETTER TO DO
1- Large size sample, multicenter study .
2- Well-designed sex and age matched study group (patient and control group)
3- Adequate duration of study.
4- To use the measured instead of estimated GFR.
5- To use prospective other than retrospective study.
The result of this study is no more valid, will you explain why?
Limitations of this study:
1-small sample size.
2-short follow up duration.
3-Racial Bias because of including predominantly whites.
4-Response and Survival Bias.
5-e-GFR by MDRD study equation.
6-absent control group.
7-High attrition rate.
This study showed that kidney donors have a similar life span and risk for ESRD compared to the general population:
The results are no more valid as:
A better design:
This study was one of basis of the myth that kidney donor have a life span and health status that is similar to that of the general population.
The drawbacks of this study are:
1- It is an observational comparative study
2- The sample technique is through stratified sampling which despite being considered a type of random sampling; it is affected by response bias. bias as the donors who can be reached out are the one who are included. I think this sampling is more like quota which is non-random sampling
3- Small number of donors only 255 is included despite the large number of kidney nephrectomies (3698) which was done throughout the study period. This made the sample unrepresentative of this population.
4- The controls were only matched for few criteria without considering other confounding which might be present.
5- There are a number of donors who died so there was survival bias. . They need to be added in the analysis (NNT). The cause of death was unknown for 162 donors
6- Most of the donors are white so the result of this study cannot be generalized.
7- The use of the MDRD study equation at the time of donation to estimate the GFR was another major drawback. It is designed for GFR that are less than 60 ml per minute per 1.73 m2. This was compared with a measured creatinine later on.so the estimation of GFR changes over the study period is not accurate.
The result of this study is no more valid, will you explain why?
1-this study is invalid as there are recent studies concluded that kidney donors have a sighnificant increased risk of ESRD.
2-the control group is general population but idealy should be living donors.
3-study group population included only white people .
4- sample size is small so if we need to make it larger study to be multicentre.
5-GFR is calculted so idealy to be measured rathe than calculation
6-serum creatinine measure at the time of eGFR idealy should be at time of donation
i would design a study , multicentre , using controls age and sex match, will follow them for longer duration and measure properly renal function and any factor which can attribute to the patient survival.
Because it needed more data to decrease bias.
It should be multicentrac, RCT, proper randomization, needed proper and ling term follow-ups.
It is a retrospective study with single center data from November 1963 to December 2007 with 3698 nephrectomies in living donors excluding patients with arterial hypertension, diabetes mellitus, and proteinuria. Although 80% of the donors were contacted, only 255 underwent the necessary new tests. Comparison with the general population becomes a major problem, due to different characteristics, after all, the first group is selected from a select group of donors compared to a predominantly obese population with metabolic alterations.
For donors who died, there is no robust data on how it happened, being restricted to comments from family members or data in the system coded by disease. Follow-up data were also restricted to periods close to 5 to 7 years, which may mask the complications resulting from transplants with longer periods.
The conclusion of this study indicates that kidney donors have a good quality of life and performance status similar to the general population, giving a false impression that nephrectomy has no consequences. Subsequent studies comparing an audience with similar characteristics for a longer follow-up period showed discrepant data.
The results of study are Invalid. As the study had many limitations
1. Small sample size
2. There is response and survival bias , only donors with available contact data or who still alive were included.
3. Most of living donors were white , this limited the generalization of results, as 14% of living donors in US are non-white
4. Using of the MDRD equation for estimation of GFR, as this formula was developed to estimate GFR less than 60 ml per minute per 1.73 m2
5. Serum creatinine was calibrated at time of study but not the time of donation
6. Lack of ideal control group
To correct weakness
1. Larger sample size
2. Ideal control group who are well matched to donors
3. Measurement of GFR rather than estimate it
4. Do multicentre studies
The result of this study is no more valid, will you explain why?
1- control group : potential donor is one who is healthy with no medical problem and will investigated so its not correct to compare the potential donor with general population 2-2- number of donors are small and from same medical center
3- Most of the living donors were white
4- using MDRD instead of CKD EPI in calculating eGFR
thanks
Long-term consequences of kidney donation:
Limitations:
1- Small size of the sample, so represent the proportion of all donors
2- The study includes only donors with available contact information who are still alive, this causes the study to be subject to both response and survival bias.
3- The majority of the donors are white, limiting the generalization of the results, although; the nonwhite donors represent only 14% in the USA.
4- The MDRD equation was developed in people with GFR < 60 ml/min/1.73 m2 and its usefulness above this level are limited. So, its use in this study adds limitations to it.
5- S. Cr was measured as well, at the time of iohexol GFR measurement, but not at the time of donation, this may result in a vague estimate of the change in the estimated GFR after donation.
6- Lack of an ideal control group. As it uses the general population for comparison, it was better to use sibling controls who were screened for donation
by these limitation the study result can not be generalized.
If I design a study I will suggest to be:
1- a prospective study over a long period
2- a large sample
3- multi centres
4- ideal control group (sibling whom did not donate but subject to evaluation during search for donor)
5- same equation for GFR estimation a donation and during the study (24h urine creatinine clearance)
6- good match of the donor and control
7- do not include dead donor with lack of information
1- More recent studies and BTS/RA Living Donor Kidney Transplantation Guidelines 2018, indicates that risk of ESKD increased by donation
2- This study has many limitations, which make it weak study and unreliable:
The current article is not valid.
· The current study founded that, the long term outcomes of donors is similar to those who were none donors as regard the decline in GFR and albuminuria.
· proteinuria was assessed as morning sample spot urine for ACR, GFR as clearance of nonradioactive iohexol and hypertension when ABP was >140/90 or need of antihypertensive medications.
· Similar mortality rates to non-donors, 1/3 mortality was due to cardiovascular mortality.
· ESKD developed in donors (related living donors with the same original kidney disease of the recipients), but similar rate to that of general population.
· This can be attributed to wide scale screening for health problems in donors.
· The current study findings cannot be validated due to the following point of weakness:
o absence of similar control group, and the comparison with general population.
o an old study involved previous studies before 2009.
o Small sample size (although 3698 donors had been assessed, but only 1 of 7 donors responded.
o Relatively insufficient period for follow up,
o use of e GFR by MDRD equation which is not valid in GFR > 60 ml/min/m2.
In order to assess the long term outcome of kidney donation , a study was conducted to include donors from 1963 through 2003 with median follow up period of 15 years post donation in. 3698 donation nephrectomies were performed in Minnesota university hospital. From 2003 through 2007 , 255 donors were evaluated for proteinuria and eGFR, blood pressure was done to evaluate for underlying hypertension.
Results of the study revealed 11 ESKD patients, with varied etiology ,ranging from Diabetic nephropathy, hypertension, interstitial nephropathy and glomerular disease.
The control group was selected from NHANES.
The outcome of the study showcased a comparable results to the control group, indicating that the life span , risk of ESKD, proteinuria and hypertension incidence in donors was similar to its incidence in general population..
The main cavate of the study was the control group . as it was heterogenous and non matching the study cohort…
This study indicates that kidney donors have a normal life span, a health status that is similar to that of the general population, and an excellent quality of life; they do not have an excessive risk of ESRD.
Questions challenging the validity of this study?
They don’t have an ideal control group, donors were matched with General population.
This study is not valid as there are many limitations of this study which are mentioned in the limitation section.
The better way of doing this study would be:
Prospective (this will minimize the recall bias)
Multicentric
Controls should be from the same population who are healthy enough to be potential donors matched for age, sex and most important ethnicity
Measurement of GFR using 24 hours urine creatinine clearance at the time of enrollment and at regular follow-up would be ideal
Creation of National level Donor registry would be ideal for such long-term studies.
The result of this study is no more valid, will you explain why?
-The small sample size which will affect the results .
– Single center study, not double blind may influence the results.
– consideting general population as control group without beeing matched in health status to donors which is fully investigated and carefully selected.
-very short follow-up period to evaluate long termeffect.
–effect of of race was neglected as all participants were white while higher risk if kidney disease is will known risk factor in African-Americans.
– using eGFR by MDRD rather than measured GFR ,also its not the best equation for healthy population .
– collecting dara through phone contact and contacting only donors who were known to be alive will affect the results greatly.
The result of this study is no more valid, will you explain why?
1. Study included small number of subjects
2. Donors were contacted who were alive (in 1:7 ratio) so survival and response bias.
3. Subjects and controls are from one ethnicity i.e. whites, so similar conclusions can’t be extended to other ethnicities or to general population
4. Use of MDRD equation for estimation of GFR to compare current and baseline kidney function
5. Control group in matched in terms of age, sex and race and not an ideal control group having characteristic’s similar to a donor (like lack of comorbidities)
The results of this study is in favor of living kidney donation with excellent long term outcomes for the donors as results of the study include:
In contrast to the results of this study, same author has conducted studies on the long-term effects of donation from donors with different risk factors and the results came out with higher risk comparing to the control groups.
The results of the study could be no more valid because of selecting general population (with different risk factors) as a control group along with bias, in addition to including patients since 1963 with possible inadequate followup or evaluation/documentation in the post donation period.
The result of this study is no more valid, will you explain why?
The lack of an ideal control group.
a small numbers of donor studied.
Its retrospective study.
Includes only white donors.
GFR not estimated.
Selection bias ,only those who have contact.
Cause of death in those who died not identified .
The use of the MDRD study equation to estimate the GFR.
Long Term Consequences of Kidney Donation:
This article address risk of ESRD in living donor from 1963 to 2007, where efforts start from 2003 to 2007 in university of minnesota.
The most of living donor has quality of life better than general population.
Life expectancy appear similar to non donor and there’s no risk of ESRD or raised creatinine level even more than 30 years post donation.
Criteria of selection donor:
In December 2003 do comprehensive efforts to contact all persons who donated kidney transplant after november 1963. Around 80% of donor was accepted to contact. They were full information regarding health status and asked for urine routine and creatinine level/ blood pressure measurements 3 times while donor seated.
All patients with blood pressure more than 140/90 considered hypertension or use anti hypertension medication.
Quality of life assessed by medical outcomes studies focus on general health survey.
Expected mortality rate was measured in comparison to general population.
Risk of ESRD in general population was calculated from 2007 by Annual data reports of united states renal data system.
Survival rate and ESRD expected post donation was similar to general population.
General health assessed by age at time of donation/ Bp measurements/ BMI and smoking/ baseline eGFR by used of MDRD equations.
Mortality rate in donor was 30% related to cardiovascular disease not from ESRD.
Low risk of ESRD seen in donor and related to hypertension and DM and few from glomerulonephritis especially in those donate to their siblings.
In this survey no donor who died had needing to dialysis or transplant.
The estimated incidence of ESRD in donor appear to be 180 per million persons per year as compared to 268 per million persons annually.
Mean creatinine level at time of donation 0.9 and eGFR 84 ml / min. mean of creatinine level after donation 1.1 & GFR 63 ml/min.
The young age at time of donation the longer time since donation and high eGFR and greater compensation but high protein creatinine excretion ratio.
The average hypertension is 122/70. Those with high blood pressure has high risk of cardiovascular disease. The risk of proteinuria associated with old age donor and high BMI.
Decline of eGFR not associated with smoking donor. However more in diabetic patients and hypertension patients.
Quality of life is excellent in donor and it’s may related to carful selected of donor in comparison to general population. Donors less likely to be smoking and less like to develop cancer.
There’s no significant difference between donor and non donor in prevalence of hypertension and DM.
Limitations of this study is small group and lack of informative data .
In conclusion, They concluded that kidney donors have a normal life span.
Good a health status similar to the general population
An excellent quality of life
No risk of ESRD because carefully selected
The rates of albuminuria and hypertension were similar to those of matched controls.
Limitations
1-the study included only a small, though representative, proportion of all kidney donors to date.
2-Only donors with available contact information who are still alive participated in this effort
3-Most of our living donors are white, a factor that may also limit the generalizability of our results, though only 14% of living kidney donors in the United States are nonwhite.
4-The most important limitation of our study is
the lack of an ideal control group.
The data offer prospective donors information regarding their life span and their risk of ESRD as compared with those of the general population, but it would be even more informative to compare their outcomes with those of sibling controls who were screened for donation and accepted as donors but did not donate a kidney, since kidney donors are carefully screened and are healthier, on average, than general-population controls.
Conclusion
1-The study indicates that kidney
donors have a normal life span
2-a health status that is similar to that of the general population, and an excellent quality of life
3-they do not have an excessive risk of ESRD.
The majority of donors in this study had a preserved GFR, and their rates of albuminuria and hypertension were similar to those of matched controls.
· Being a retrospective analysis carries much bias
· The study had included 80% of the donors, not all as many had died.
· The control group included the general population based on Human Mortality Database, which combines data regarding survival and death rates from the National Center for Health Statistics with data from other sources, which means the included general population have many comorbidities. Similarly, the rate of ESRD in the general population was obtained from the 2007 annual data report of the United States Renal Data System.
· It should include donors from multicentric trials
The result of this study is no more valid, will you explain why?
1- the study included a small fraction of all kidney donors (1 out of 7 donors). the included donors were only those who are still alive and whose contact numbers were available.
2- most of the included donors were white that limits the generalization of the results of the study.
3- the use of MDRD study equation for eGFR as this equation was developed for people with GFR less than 60 ml/min.
4- serum creatinine was calibrated at the time of measuring GFR but not at the time of donation. therefore, there were imprecise estimates of changes in GFR post-donation.
5- lack of ideal control groups. the study included general populations as control groups. it was better to use sibling controls who were screened for donation and accepted as donors but they didn’t donate. these potential donors are presumed to be more healthier to the general population.
· The result of this study is no more valid, will you explain why?
The study is not valid in view of certain limitations:
1) There is lack of an ideal control group: the study used general population as controls, who would be less healthy than the study population (donors) selected after intense evaluation.
2) The sample size was small
3) The follow-up was of short duration.
4) The study population included predominantly whites, hence racial bias present
5) The study had response and survival bias
6) The GFR was calculated using MDRD study equation
7) There was high attrition rate
8) Most importantly, another study published later-on did compare outcomes of donors with healthy non-donors, invalidating the findings of this study by overcoming a major limitation.
The excellent optimistic results showed close similarity in survival between donating and non-donating people, which was shown to be inaccurate in later papers. Limitations of the study like relatively smaller number compared to other studies and dependence on already available data limited by the availability of contacts as reported by the writers. Accordingly, both response and survival bias are considered. Ioxehol clearance is not a standard or practical nowadays.
This study can be redesigned as a randomized trial. only 255 donors underwent measurement of the GFR. This is not representative.
This study indicates that kidney donors have a normal life span and an excellent quality of life; they do not have an excessive risk of ESRD with preservation of GFR
but certain limitations in this study which are listed below
That is a good use of bold type for the sake of emphasis, dear Dr Huda.
That is a good use of bold type for the sake of emphasis, dear Dr Rihab.
The result of this study is no more valid, will you explain why?
That is a list of good suggestions. Dr Alaa.
The result of this study is no more valid, will you explain why?
– The study indicates that kidney donors have a normal life span, a health status
that is similar to that of the general population, and an excellent quality of life; they do not have an excessive risk of ESRD. The result of this study is no more valid because :
1.The study included only a small, though representative, proportion of all kidney donors to date and only donors with available contact information
who are still alive participated in this effort .
2.Analysis is subject to both response and survival bias.
3.The lack of an ideal control group.
4.Most of living donors are white, a factor that may limit the generalizability of results .
5.The use of the MDRD study equation to estimate the GFR which was developed in people with a GFR of less than 60 ml per minute per 1.73 m2, and the usefulness of the equation above this level is limited.
6.Serum creatinine was calibrated at the time of measurement of the iohexol GFR but not at the time of donation, a factor that may have resulted in imprecise estimates of the change in the estimated GFR after donation.
That is a good analysis, Dr Younis.
This study had limitations. First of all, selection bias by selecting a small percent of all donors and only those who were alive or had contact information were studied.
Most donors were white that increase selection bias. In addition, using MDRD equation for evaluating GFR was not appropriate. GFR measurement by iohexol was only done in a low present of donors’ post-donation and not before donation that limit comparison of GFR before and after donation.
Control group was not ideal, too. Using sibling controls would be better. Multi-central study with large number of donors will be more informative.
That is a good analysis, Dr Nasrin
The result of this study is no more valid, will you explain why?
The study design had many limitations:
People: include reactively small numbers, white only, single-center and optimum donors.
Intervention: depended on recalls for the recipients about their donors’ information, no solid data about all donors and their follow up including dead donors and those who were unable to connect with them.
Comparison: with the general population whatever their comorbidities and their risks for ESRD
Outcome: many outcomes were searched i.e. (survival, proteinuria, HTN, quality of life ) and were not looked for in all participants
Time: short time period for follow up
That is a list of good suggestions. Dr Ellisy
Sir,
This study is not valid as there are many limitations of this study which are mentioned in the limitation section.
The better way of doing this study would be:
That is a list of good suggestions. Dr Patil, especially a national level donor registry.
This study is no more valid for many reasons:
1-The control group is not like study group, donor. This is because donors were highly selected, healthier, and followed up not like general population, some of whom may have undiagnosed medical problems.
2-Donation period was relatively older 1963 to 2007 at time where investigation and surgery may be different from current practice.
3-Follow up after donation is shorter for healthy donors to show effect on the kidney or cardiovascular disease.
4-Number of donors is relatively small.
5-Most of donors are white.
This study is not valid because :
That is a good analysis, Dr Nandita.
However, I could not understand why use of statistical software influence the interpretation.
Don’t have an ideal control group. The study included only a small number of donors in single center. Only donors with available contact information who are still alive participated in this effort. Therefore, the analysis is subject to both response and survival bias.
The use of the MDRD study equation to estimate the GFR is limited by the fact that this formula was developed in people with a GFR of less than 60 ml/minute/1.73 m2, and the usefulness of the equation above this level is questionable.
Majority of donors were white so the result might not hold true for other races. In addition to that, average age of general population is different in different parts of world which can impact these results.
Dear Dr Eusha,
I agree with limitation ‘the lack of ideal control group’, in this paper that you describe.
# The result of this study is no more valid, will you explain why?
*The study included only a small number of donors in single center. Only donors with available contact information who are still alive participated in this effort (a rate of one of seven selected donors). Therefore, the analysis is subject to both response and survival bias
*Excluding donors who were foreign nationals, the survival of donors appeared to be similar to that of the controls in the general population, but survival could not be formally compared, since life tables from the National Center for Health Statistics do not provide confidence intervals for the probability of survival in the general population.
* Most of the living donors are white that limit the result, a factor that may also limit the generalizability of the results.
*The use of the MDRD study equation to estimate the GFR for the comparison of current and baseline rates, which is not suitable for the GFR less than 60 ml per minute per 1.73 m2.
*Serum creatinine was calibrated at the time of measurement of the iohexol GFR but not at the time of donation a factor that may have resulted in imprecise estimates of the change in the estimated GFR after donation. .
*The lack of an ideal control group, data offer prospective donors information regarding their life span and their risk of ESRD as compared with those of the general population, but it would be even more informative to compare their outcomes with those of sibling controls who were screened for donation and accepted as donors but did not donate a kidney, since kidney donors are carefully screened and are healthier, on average, than general-population controls.
Dear Dr Elaf,
I agree with limitation of this paper that you describe ‘the lack of ideal control group’.
This study studied the long term consequences of kidney donation & risk of ESRD in donors & non donor population which revealed that no risk of ESRD on account of albuminuria , preserved GFR & quality of life in comparison to general population .This study is no more valid as it is a single center study with small sample(3698 kidney donors) and results can not be generalized because of white population only. The control group is not ideal as general population is not healthy and also MDRD equation for GFR estimation is considered as validity above GFR 60 ml/min/1.73m2 is limited and creatinine not caliberated at the time of donation. Response and survival bias is present in the study as only alive donors with available contact information were included. Data mainly reported by the donors or recipients themselves.
Dear Dr Butt,
I agree with limitations of this paper that you describe biases and ‘the lack of ideal control group’.
Long-Term Consequences of Kidney Donation
1. The study ascertained the vital status and lifetime risk of ESRD in 3698 kidney donors who donated kidneys during the period from 1963 through 2007 at the University of Minnesota.
2. In a 255 donors, from 2003 through 2007, the study parameters for evaluation were:
a) The measured glomerular filtration rate (GFR) and urinary albumin excretion to overcome the limitation of the previous studies.
b) Prevalence of hypertension.
c) General health status and quality of life.
Study’s result and conclusion
1. Survival and risk of ESRD are similar between donors and the general population.
2. Donors had a lower estimated GFR, lower systolic blood pressure, and a lower urinary albumin excretion rate in comparison to the general population.
3. Self-reported diabetes and use of antihypertensive medications were similar in the two groups(donors and non-donors).
4. The life span of kidney donors is similar to that of persons who have not donated a kidney.
The result of this study is no more valid, will you explain why?
1. The confidence intervals for the probability of survival in the general population was not provided by the national center for health, so the survival wasn’t formally compared.
2. The study included only a small proportion of all kidney donors.
3. The analysis is subject to both response and survival bias (a rate of one of seven selected donors).
4. Most of the living donors were white, which may limit the generalizability of the results.
5. The used MDRD formula is not useful when the GFR is > 60( the formula was developed for those with GFR <60).
6. The calibration of SCr to measured GFR using iohexol, wasn’t at the time of donation. This may have resulted in a change in the estimated GFR after donation.
7. The have a lack of an ideal control group(the ideal control group is those who screened as potential donor and didn’t donate).
Dear Dr Assafi Mohammed,
I agree with long list of limitations that you have highlighted in this paper
This study indicates that kidney donors have a normal life span, a health status that is similar to that of the general population, and an excellent quality of life; they do not have an excessive risk of ESRD.
Questions challenging the validity of this study?
They don’t have an ideal control group, donors were matched with General population.
The use of the MDRD study equation to estimate the GFR is limited by the fact that this formula was developed in people with a GFR of less than 60 ml per minute per 1.73 m2, and the usefulness of the equation above this level is limited.
The study analysis is subject to both response
and survival bias.
Majority of donors were white so the result might not hold true for other races, at the same time average age of general population is different in different parts of world which can impact these results.
Dear Dr Nabi,
I agree with limitations of this paper that you describe biases and ‘the lack of ideal control group’.
This was the study where recruitment of cases was done where donors donated between 1963-2007. So as such in the research world the study is quite old.
But I think the major reason which made study currently invalid is because of taking general population as controls and stating that kidney donors have similar life span like general population with almost same risk of developing ESKD in remaining kidney.
this in current era is almost clear that donors are super selected and they are much more fit than general population so even if we take age, gender, BMI, etc matched controls from general population, the study is erroneous.
Other factors like, single center, small number of cases, self reporting, etc. seem to be the usual limitations which every study has one or the other.
If I consider about tools of analysis, then the researchers used the best available at their time though they have become obsolete or invalid in current era like:
Dear Dr Saini,
I agree with limitations of this paper that you describe reporting biases and ‘the lack of ideal control group’.