II. Long-term risks for kidney donors
This is one of the key articles that changed our understanding of the risk of donation.
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- Please summarise this article in your own words
- How did they reach this conclusion?
This is one of the key articles that changed our understanding of the risk of donation.
Dear All
This article in addition to other few similar articles changed our practice in the UK. They did not use the general population as a control.
What is the disadvantage of using the general population as a control group?
Using the general population as a control group will lead to bias in the result. as the general population have underlying chronic diseases(CKD, Cardiac, diabetes, HTN and stone former). If you need to compare, should use a healthy population(medically free) of the same age, ethnicity and gender to avoid false results.
In that case what would be an (almost) ideal control for LRDs?
any person who has no contraindications for a donation could be included in the control group. As in this study, the Controls included from the Health Study of NordTrndelag (HUNT) population study are ideal.
ideal control is the one who has been already selected for donation, but excluded for recipient related issue like ABO or HLA incompatibility or complex vascular anatomy.
The ideal control for the donor group would be those who had one-sided nephrectomy for non-malignancy causes or for an incidentally detected very small tumor.
Any comments?
You do not have to agree with me, just because I am a faculty member on this course (fellowship).
those unilateral nephrectomy for non malignancy reasons or small tumour, for me, is similar to general population group. So, will have same bias, they could have underlying renal disease, diabetes, proteinuria etc. Unless we say will look at their lab and clinical data and exclude those with issues that would make them unsuitable donor. Still for me will be less ideal than those investigated as potential donors and approved by the transplant committee, however they did not donate at the last moment.
Dear Dr Sharma,
I agree with Dr Muntasir Mohammed that subjects with unilateral nephrectomy can have other associated diseases such as DM, hypertension, or any other systemic disease that may affect the remaining kidney. Unilateral nephrectomy is usually performed as an obligation secondary to a serious disease, which represt a different situation compared to electively donating a kidney after a meticulous evaluation of the donor’s history, general condition and kidney functions.
Furthermore, the persons who live with a single kidney after a unilateral nephrectomy will have the same risk factor under investigation in healthy kidney donors (which is, does the donation of a kidney and living with a single kidney will lead to a negative outcome that would not happen if the donor continued living with his both kidneys?). So, I believe that the control group for evaluation of the impact of donation on the donor outcome should be healthy subjects in the same age group who would have been accepted for kidney donation due to lack of any health-related contra-indication for kidney donation
(LRD): what does the R stands for? living related donors or living renal donors?
The ideal control for living related donors would be other family members of matching age who would be eligible for kidney donation.
You are so right Dr Elamin. LRD is the abbreviation of ‘living-related donation. But it becomes a misnomer for all living donation by family members.
Living donor is one of general population but he undergoes several laboratory and imaging tests and he is selected under strict control .
Otherwise, general population group may contains people with higher risk (mild stage of CKD, DM, CVD…)
The two groups are not equal therefore bias may affect results
As general population controls have coexisting medical conditions such as cardiovascular disease, malignancy, diabetes, hypertension, and chronic kidney disease were included that led them to an appropriate comparison with living donors who are very carefully selected so bias control will affect the results
So control group should be selected in a similar manner to living donors
Criteria for donors selection allows detailed examination and investigations to confirm good donor health
So comparing such healthy individuals with general population with all variations in comorbidities ( DM ,HTN ,Obesity, smoking, cardiovascular disease, dyslipidemia….etc)that affects renal function ,cardiovascular events and mortality would be inaccurate
Living donors is a highly selected cohort of patients based on their absence of comorbidities and longevity of GFR post donation. The general population, if selected as controls, can include patients with co-morbidities like CKD, DM, Uncontrolled hypertension, pre-existing CVD and malignancy, introducing a bias and giving a falsely lower incidence of mortality and progression to ESRD
The general population is a less healthy group than the – thoroughly investigated, meticulously screened, donor population.
In short general population may be less healthier than the donor
because if take general population as a control group , it will underestimate the incidence of the risk of ESRD and all cause mortality in donors group because the general population include many of hypertensives and diabetics whom prone to kidney disease and of course other disease which leads to kidney disease and ends by ESRD.
but the selected control are donors but not donating , i mean all preliminary investigations were done and history was taken from them and decided to be donor but without donation
General population may have medical problems that may increase the cardiovascular and overall mortality in this group, on the other hand donors are perfectly selected and should be healthy and free of any medical illness, so in order to have accurate results it is better to compare donors to healthy non donors and not to the general population.
Disadvantages include , is that parameter used in the previuos study that conclude , no difference in ESKD, CVD, all cause mortality , because those general population they have their own cause to develop CKD and CVD and All cause mortality , as acomplication of general risk factor , not in comparing to donor , which have single kidney .
In contrast to the studies that use selected group with exclusions, and have eligability to donate , so compared tow group with the same criteria , but the difference is in the nephron mass, and its associated endocrine, neuroendocrine, autoregualtion process inside the kidney, extrarenal and environmental factors.
it underestimates the prevelance of esrd, cardiovascular and long term complication after donatio and causes a bias in the results
General population may have medical conditions which may bias the long term risk of kidney donors
Using general population as control would not be ideal because entire population is not potential donor. many harbour one or the other disease which makes the person unsuitable for donation and only few become eligible for donation.
Hence, when we are evaluating long term outcome of kidney donation where cases are those who have already donated kidney, then the controls should be those who can become eligible donors and not the general population.
The disadvantage of use of general population is the selection bias gap, in base line characteristics, in general population there may be whom wont be a potential donor.
If general population are considered as a control group cohort, then the criteria pondered to select the investigated group will not be matched as the general population group is heterogenous with variable confounding features that biased the comparison towards the investigated group. Therefore, proper selection of the control group has to be stratified to match the criteria for selection considered for investigated group.
Disadvantages
-Need accurate sampling frame
-Time consuming, expensive, hard to contact and get cooperationMay remember exposures differently than cases.
general population may be less healthy than selected donor so the result will be not that accurate in comparison we must use a control with sAme createria of that in the study
The general population are begone with numerous unidentified health challenges that may not be known hence creating a bias in primary or secondary outcome of a study that was compared with those that were well screened before accepted to donate
The disadvantage of general population is that it may include adults with medical conditions making them less healthy than the donors who undergo detailed medical evaluation. So, there is a selection bias, giving advantage to the donors.
I believe that from one population to others there are certain genetic variations and even lifestyle behavior that can influence one’s behavior and as such these studies must have control from their own native country. It will give a better understanding of what is occurring.
Single center study used around 1091 donors with median GFR around 104 ml/min/m2 and control group of 32000
Exclusion criteria: age more than 70 or younger than 20, BMI more than 30 , BP more than 140/90, GFR less than 70 or pt on anti hypertensive.
Follow up for 15
And found that donors are high risk for ESRD and CV complications
Limitations:
Only single study
Data related to one country only and white people
They may have different risk factors. the best is both groups hold the same inclusion and exclusion criteria.
The disadvantages of using the general population as a control group of living kidney donors caused by the fact that kidney donors represent a selected subgroup, who proved healthy and suitable for donation. On the other hand, the general population includes many persons with variable systemic diseases which may cause progressive CKD and ESRD (e.g. DM, Hypertension, variable auto-immune disorders, etc.)
Therefore, the outcome of kidney donors should be studied in comparison to a similar population (i.e. subjects in the same age group who would have been accepted for kidney donation due to lack of any health-related contra-indication for kidney donation).
Disadvantage of using general population as control is that it would lead to selection bias.
This is because the control group may in fact not be similar to the donors, and may be less healthy than them. This could lead to skewing of study results in favor of kidney donation.
the living kidney donors are highly selected healthy persons , that mean the disease which may be barrier to donation is excluded but the general population is associated with many common disease that may affect renal and overall outcome and mortality.
this means that the general population is an unaccepted control for the donors .
general population could develop health issues affecting their cardiovascular ,renal status or even survival more than adequately selected group that are eligible to donate , resulting in bias .
Choosing a control group from the general population will include patients whore may not be eligible and accordingly should be discarded from the donation. Those not eligible for donation are readily increasing the odd ratio of donors (which is actually overestimation real rate)
In this study, they compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation. All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years.
There was a significant corresponding increase in cardiovascular death to
1.40 (1.03–1.91), while the risk of ESRD was greatly and significantly increased to 11.38 (4.37–29.6). The overall incidence of ESRD among donors was 302 cases per million
and might have been influenced by hereditary factors.
Immunological renal disease was the cause of ESRD in the donors.
Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been elegible for donation
Living kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group with a median follow-up of 24.9 years. Hazard ratio for all-cause death was significantly increased to 1.30 (95% confidence interval 1.11–1.52) for donors compared with controls. There was a significant corresponding increase in cardiovascular death to 1.40 (1.03–1.91), while the risk of ESRD was greatly and significantly increased to 11.38 (4.37–29.6). The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors.
This study compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors with a control group of individuals who would have been eligible for donation.
Living donor kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), because it is associated with improved graft and patient survival compared with transplantation from a deceased donor.Living kidney donation, however, requires that healthy individuals voluntarily undergo major surgery with no physical health benefit to themselves. Although rare, perioperative mortality does occur during organ retrieval from living donors and have been estimated to occur in 0.2% of liver donors and 0.03% of kidney donors. Less serious perioperative risks are accepted and well documented.
Our analysis demonstrated a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the criteria for donation.
Several studies have reported that increased BP, albuminuria, and reduced renal function are associated with increased all-cause and cardiovascular mortality. These risk factors are more prevalent in kidney donors following nephrectomy. As a result, concerns have been expressed that kidney donation could lead to increased cardiovascular morbidity and mortality. Despite the inevitable reduction in renal function after nephrectomy, and evidence from the general population, it appears that the medical community has not regarded loss of renal function in living kidney donors as a long-term risk factor for mortality and cardiovascular disease.
Due to missing data for smoking (27.4%), systolic BP (6.3%), and BMI (17.3%), survival analyses were repeated after replacing missing data using multiple imputations.24 Missing values were estimated based on known covariates and outcome variables; 20 sets were created and pooled for analysis. Final multivariate analyses after multiple imputations, shown in the tables as ‘adjusted , were considered the main analyses. To enable construction of a survival curve, matching on age, gender, systolic BP, BMI, and smoking was done using coarsened exact matching. After multiple imputations and matching, survival curves were constructed adjusted for year of inclusion. For the outcomes of ESRD and cardiovascular mortality, competing risks were assessed by sensitivity analysis and competing risk regression.In accordance with some center’s practice for pre-donation renal function, Cox regression analyses were repeated with a cutoff for eGFR of 80ml/min per1.73m2, which did not change our results
Long-term risks for kidney donors :
Follow up studies of Living organ donors have not been associated with an increase in cardiovascular or all-cause mortality, but the results of these studies may have been skewed due to selection bias in the control groups. The majority of studies included general population controls, which included persons with medical issues that would disqualify them from kidney donation.
These controls would have been less healthy than the living donors as a result, which could have led to an underestimation of the impact of organ donation on cardiovascular and all-cause death.
This study compare the long-term renal function and cardiovascular and all-cause mortality in living kidney donors with a control group of individuals who would have been eligible for donation.
1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years were identified for All-cause mortality, cardiovascular mortality and ESKD .
A 32,621 potentially eligible kidney donors was selected as control group with a median follow-up of 24.9 years.
In comparison to a chosen sample of non-donors who would have been eligible for donation, our data showed a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation.
The use of living donor kidneys has become commonplace despite the fact that there is a known risk of perioperative mortality and a minor chance of significant complications from the surgical intervention.The control group in the vast majority of published studies has been an unselected general population.
the inclusion of controls with preexisting medical conditions that would have disqualified them from kidney donation, such as cardiovascular disease, cancer, diabetes, hypertension, and chronic kidney disease, skewed the results in favor of the donor cohorts. It is obvious that living donors are chosen with great care, and the right comparison group should also be chosen with care.
With increasing rates of kidney donation from living donors nowadays, the need to establish the long-term sequences of kidney donation is needed to be fulfilled. Short term and perioperative complications are rare among the kidney donor s . But rate of long term sequences and complications as HPN , proteinuria, decrease in GFR are not well established and their incidence is variable among the studies
Previous studies reported no long term complications related to kidney donation but those studies were limited as they compared the donors with less healthier controls and they has relatively short follow up periods.
In this randomized controlled study , the investigators compared the kidney donors with non donors who were elligable for donation ( so both donors and non donors have close characteristics), the comparison was related to CV complications, CKD and ESRD risk and all cause mortality.
The median follow up period was 15 years from 1963-2007 and included 32621 controls (Controls were included from the Health Study of Nord Trendelag (HUNT) population study and 2269 living donors.kidney donations were per-formed at Oslo University Hospital. ESRD was diagnosed in 1009 with rate of 302 case per million with significant increase in ESRD incidence among donor compared with controls , while there was increase in risk of CV complications and death among the donors . while there was 224 deaths among the kidney donors compared to 2425 deaths among the 32,621 controls, 28.4% of which were due to cardiovascular disease. No donors died during or immediately post operative period after the surgical procedure.
Conclusion
– perioperative complications after kidney donation are rare
-Kidney donation is associated with slightly increased risk of ESRD, CVD and all cause compared with matched healthy controls but lower than the general population.
This is a Norway study of 1901 donors(1519 were first-degree relatives, 89 were other relatives, and 293 were unrelatedover a median follow-up time of 15.1 (1.5–43.9) years. a control group of 32,621 was constructed with a median follow-up time of 24.9 (0.1–26.0) years.
During the observation period, there were 224 deaths among 1901 kidney donors from the initial inclusion group, 68 (30.4%) of which were due to cardiovascular disease. There were 2425 deaths among the 32,621 controls, 688 (28.4%) of which were due to cardiovascular disease. No donors died during or immediately after the surgical procedure.
The unadjusted death risk associated with kidney donation was 2.49. In adjusted complete case analysis, the HR for kidney donors was 1.48. There was a corresponding increase in cardiovascular mortality. A total of nine donors (0.47%) developed ESRD. All were family members. Median time from donation was 18.7 (10.3–24.3) years. Renal failure in donors was mainly caused by immunological diseases: glomerulonephritis, systemic lupus erythematosus, Wegener’s granulomatosis, ANCA -positive vasculitis, sarcoidosis and diabetes/nephrosclerosis. In the control group, 22 individuals developed ESRD. Reported causes were glomerulonephritis, pyelonephritis, polycystic kidney disease, hypertension, diabetes, amyloidosis, systemic lupus erythematosus, drug induced nephropathy, medullary cystic disease and unknown. The crude incidence of ESRD in donors was 302 per million person-years. The overall incidence rate for development of ESRD in Norway is about 100 per million per person-year. After multiple imputation of missing values, the estimated HR for ESRD in kidney donors was 11.38 (4.37–29.63, Po0.001)
The strength of this study:
1. complete follow-up of all donors and controls with certified causes of death.
2. In the majority of patients, data were available regarding BMI, smoking, and BP, three major cardiovascular risk factors.
3. the longer follow-up time and the larger number of events.
Living donor kidney transplantation is the best treatment for end-stage renal disease because it provides greater graft and recipient survival when compared to deceased donation. When compared with the general population, the act of donating a kidney does not increase the donor’s mortality or loss of kidney function.
However, when compared with the healthy control group, which met the criteria for donation, for the donor group it is clear that there will be a loss of kidney function, in addition to proteinuria and increased blood pressure levels greater than expected for normal aging. Thus, there is a potential increased risk of long-term loss of renal function and increased mortality from cardiovascular causes.
These results imply a decisive ethical posture of informing the donor of these risks, providing them with more reliable information with reality.
With regard to perioperative risk, the donation of living kidneys is associated with a known low risk of perioperative mortality and a small risk of major complications related to the surgical intervention..
Changing the control group was sufficient. Rather than considering the general population, donors were compared to a healthier group of non-donors who would otherwise be eligible for donation.
Introduction:
donor kidney transplantation is the preferred treatment ESRD, because it is associated with improved graft and patient survival compared with transplantation from a deceased donor.
Living kidney donation, however, requires that healthy individuals voluntarily undergo major surgery with no physical health benefit to themselves. Although rare, perioperative mortality does occur during organ retrieval from living donors and have been estimated to occur in 0.2% of liver donors and 0.03% of kidney donors.2,3 Less serious perioperative risks are accepted and well documented.
Kidney donation inevitably leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in blood pressure greater than that attributable to normal aging.
These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population.
In most studies, controls were selected from the general population, which includes adults with medical conditions that would make them ineligible for kidney donation.
As a result, these controls would have been less healthy than the living donors and an effect of organ donation on all-cause and cardiovascular mortality could have been underestimated.
The aim of the present study :
was to estimate long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control group screened for eligibility for live-kidney donation.
RESULTS :
During 1963–2007, 2269 live-kidney donations were performed at Oslo University Hospital. After excluding marginal donors, 1901 donors were included . Among these, 1519 were first-degree relatives, 89 were other relatives, and 293 were unrelated. Median follow-up time was 15.1 (1.5–43.9) years. eGFR at donation was 104.7 ml/min per 1.73 m2.
Controls were included from the Health Study of NordTrndela population study. Out of the 74,991 individuals participating in this population-based survey, a control group of 32,621 was constructed to fit criteria for kidney donation , Median follow-up time for the control group was 24.9 (0.1–26.0) .
there were 224 deaths among 1901 kidney donors from the initial inclusion group, 68 (30.4%) of which were due to cardiovascular disease.
There were 2425 deaths among the 32,621 controls, 688 (28.4%) of which were due to cardiovascular disease. No donors died during or immediately after the surgical procedure.
Discussion:
significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the criteria for donation.
Living kidney donation is associated with a known perioperative mortality risk3 and a small risk of major complications related to the surgical intervention.
Limitations of the study:
Donors from one county control from all country.
Donors long time follow up.
Control renal function not identified.
Level of education also not known for control ,other cofounder s factors.
Our results may be difficult to extrapolate to unrelated donors and non-Caucasians.
The strength of our study is complete follow-up
complete follow-up of all donors and controls with certified causes of death.
In the majority of patients, data were available regarding BMI, smoking, and BP, three major cardiovascular risk factors.
The major difference between our study and the studies by Garg et al .and Segev et al.is the longer follow-up time and the larger number of events.
How did they reach. This conclusion ?
By selection of matched controls and long time follow up.
Long-term risks for kidney donors
Living donor kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), it is associated with improved graft and patient survival compared with transplantation from a deceased donor. Living kidney donation, however, requires that healthy individuals voluntarily undergo major surgery with no physical health benefit to themselves.
Previous studies have suggested that living kidney donors maintain long-term renal function and experience no increase in cardiovascular or all-cause mortality. However, most analyses have included control groups less healthy than the living donor population and have had relatively short follow-up periods. Here we compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation. perioperative mortality from living donors and have been estimated to occur in 0.03% of kidney donors.
Kidney donation inevitably leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in blood pressure (BP) greater than that attributable to normal aging.5,6 These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population.
The aim of the present study was to estimate long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control group screened for eligibility for live-kidney donation.
Results:
demonstrated a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the criteria for donation.
This is a long prospective cohort study to verify the long-term complications(all-cause mortality, Cardiovascular mortality and ESKD) post donation.
The living donors for kidney transplants have been followed between 1963- 2007 were compared to the control group of non-donors eligible for donation ( matched with the living donors’ group by age, sex, smoking status, BP, BMI) and not the general population who may have medical problems that may increase their risk of cardiovascular and overall mortality. Additionally, donors were followed for a long time (mediation duration of 15 years).
Results:
A higher rate of all death risk, more CVD risk and ESRD risk the in donor groups compared to the control group(7 /of 9 donors) progressed to ESRD requiring RRT due to primary renal disease which can be explained by the genetic risk factors in related living donors (first-degree) and not only the nephrectomy effect.
The findings raise some medical and ethical considerations regarding live-kidney donation. Potential donors should be informed of increased –small –risks associated with donation in short and long-term.
Conclusion:
Continue to encourage living kidney donation for those willing to donate. However, medical and ethical concerns should be considered including good selection criteria, addressing the genetic risk factors in related kidney donation, and discussing the short and long term risks.
this study aimed to find out the overall risk of donation, risk of ESRD, and cardio-vascular risk.
Methods:
This is a single center study.
Large number of medically and physically fit kidney donors. Living related and unrelated donors. With median GFR at the time of donation 104 ml/min/m2.
Total numbers of included healthy donors 1091, control group 32000 matched control group.
Exclusion criteria: Donor’s age>70 or <20, BMI>30 or <17, BP>140/90 or on anti-hypertensive medications, GFR<70 ml/min/m2.
Median follow up duration: 15 years.
Results:
The donor group showed higher hazard ratio of overall death, rate of ESRD and cardiovascular complications compared to the control group.
Discussion:
During the first decade of follow up there was no difference between the two groups which was matching with other observational studies with short follow up periods (2-6 years).
Longer follow up revealed that donors are more liable to develop hypertension, proteinuria and decline of GFR which lead to more incidence of cardiovascular complications in the donor group.
The incidence of ESRD was higher in the donor group compared to the control group.
Limitations of the study:
1- Single center study.
2- Data is related to white population only in one country.
3- In control group: no data regarding renal function and proteinuria and unmeasured confounders like co-morbidities.
Q1:
In this article, all-cause death, cardiovascular death and ESKD rates of 1901 donors from 1963 to 2007 who were followed for 15.1 years were compared with a control group of 32621 healthy individuals that were screened as donors and followed for 24.9 years. The risk of cardiovascular death and ESRD among donors was 1.4 and 11.38 compared with healthy controls which was significant. Donors had an incidence of 302 per million and the most prevalent etiology for their renal disease was immunologic diseases.
Q2:
Last studies had a selection bias for control group that was chosen from the general population, but in this study, healthy control group with comparable health status was selected.
Long-term risk of the kidney donor
Introduction
Kidney transplantation is the best treatment for ESRD. Living donor kidney transplantation offers the best outcome as compared to a deceased donor. This requires healthy individuals who voluntarily undergo major surgery with no benefit to themselves. During organ retrieval, rare perioperative mortality does occur. Kidney donation can lead to reduced renal function and is associated with increased proteinuria and a rise in blood pressure. These can increase cardiovascular risk and all-cause mortality in the general population. these effects may be misleading, as, in most studies, control groups were selected from the general population, and included adults with medical conditions that exclude them from the donation. So, these controls are less healthy than the living donors and the effect of organ donation may be underestimated. Three studies include controls that have comparable health status to living donors, and they found no increase in cardiovascular disease or mortality over 6 years of follow-up. Longer follow-up time may be necessary to examine the possible impact of a living donor. ESRD also develops in living donors, although the absolute number of cases is very low.
The aim of the study was to estimate the long-term risk of living kidney donation compared with the selected control group.
Results:
1901 donors were included. The Median follow-up time was 5.1 (1.5—43.9) years.
The mean e GFR at donation was 104.7 ml/min/1.73 m2
32,621 controls were constructed to fit the criteria for kidney donation.
In the donor’s group, there was 30.4% death due to cardiovascular disease as compared with 28.4% death in the control group due to cardiovascular disease.
Nine (0.47%) of donors developed ESRD. All were family members. The median time was 18.7 (10.3—24.3) years. It was mainly caused by immunological disease. Glomerulonephritis (n ¼ 3), systemic lupus erythematosus (n ¼ 1), Wegener’s granulomatosis (n ¼ 1), ANCA (anti-neutrophil cytoplasmic antibodies)-positive vasculitis (n ¼ 1), sarcoidosis (n ¼ 1), and diabetes/nephrosclerosis (n ¼ 2).
In the control group, 22 individuals developed ESRD. Reported causes were glomerulonephritis (n ¼ 5), pyelonephritis (n ¼ 4), polycystic kidney disease (n ¼ 4), hypertension (n ¼ 3), diabetes (n ¼ 1), amyloidosis (n ¼ 1), systemic lupus erythematosus (n ¼ 1), drug-induced nephropathy (n ¼ 1), medullary cystic disease (n ¼ 1), and unknown (n ¼ 1).
Discussion:
There is a significant increase in ESRD, cardiovascular, and all-cause mortality after living kidney donation compared to a selected population of non-donors. Living donation is also associated with perioperative mortality risk and surgical complications. Garg et al. in two studies found no survival difference between kidney donors and a selected control group. Segev et al. study also found that donation was not associated with an increase in all-cause mortality.
The incidence of ESRD in our study was comparable to that seen in some previous studies, although the incidence of ESRD in kidney donors is assumed to be lower than that in the general population. the present study demonstrates a substantial increase in ESRD risk after donation. The causes of ESRD were
different in donors and controls.
Study limitations:
1- All controls lived within one county, whereas kidney donors were drawn from all over Norway.
2- Missing renal function data in the control group, which may influence the observed increased risk in the donors.
3- Longer follow-up time in controls may have influenced the detection of ESRD cases.
Introduction
Renal transplantation by far is considered the best solution for ESRD whereas living renal donation is accompanied by more impressive outcomes than deceased donation in terms of graft survival and patient survival as well.
Living donation carries the risk of unnecessary major operation from the donor aspect without marked benefit for the donor itself. Perioperative mortality rarely occurs of 0.03% of kidney donors, which is still a point of concern.
The increased risk for cardiovascular and all-cause mortality is attributed to the development of proteinuria and HTN mainly. Follow-up studies of living donors may have selection bias concerning the control groups. Controls could have been less healthy than the actual living donors. It is also possible that the duration of the studies has been less than the time required for the harmful effects of donation could be manifested for instance exceeding 6 years. Development of ESRD among donors was observed after long term donation with very low number of cases.
The goal of this study was to determine the presence of long-term all-cause mortality, cardiovascular mortality, and risk of development of ESRD in donors compared to a selected screened control group eligible for living renal donation.
RESULTS
In this study, 1901 donors were included from 1963 till 2007 at Oslo University Hospital with mean eGFR at donation was around 104.7 ml/min per 1.73m2. Control group of about 32,621 individuals matching the criteria for renal donation. Median follow-up period for the control group was 24.9 years. All donors were Caucasians.
In January 2010, outcome data on all-cause mortality and renal replacement therapy were evaluated for both donors and the control group. It was found that 224 deaths among 1901 donors of about 68 (30.4%) of which were attributed to cardiovascular disease. On the other hand, 2425 deaths among the 32,621 controls, 688 (28.4%) of which occurred due to cardiovascular disease. There were no donors’ deaths during the perioperative period due to surgical procedure.
The survival curves showed significant difference (P value less than 0.001). The unadjusted hazard ratio (HR) for death risk that was associated with renal donation was estimated about 2.49 (95% confidence interval (CI), 2.13–2.91, P value less than 0.001).While, the adjusted HR for kidney donors was 1.48 (95% CI, 1.17–1.88, P value equal to 0.001).Finally, there is elevated risk for cardiovascular mortality (HR 1.40, 95% CI 1.03–1.91, P value is 0.03).
Unfortunately, nine donors (0.47%) developed ESRD who were also family members. Median time from donation was around 18.7 (10.3–24.3) years attributed mainly to development of immunological causes. On the other aspect, among the control group 22 individuals developed ESRD also due to immunological reasons as well as other renal diseases as APKD, pyelonephritis and drug induced nephropathy.
The HR for ESRD in donors was estimated by 11.38 (4.37–29.63, P value less than 0.001).
DISCUSSION
According to this study, a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living donation was clearly demonstrated.
A study conducted by Garg et al. of follow up 6 years of donors revealed no survival difference between renal donors and the selected control group. Another study performed by Segev et al. proved that donation was not associated with an increase in all-cause mortality for follow up of 6 years interval.
This study also observed no increase in all-cause mortality during the initial 5–10 years post renal donation, however the survival curves then started to deviate ensuring the need of longer follow up duration studies.
This study also observed that the donors might have a potentially higher risk for ESRD development compared to selected controls. Seven out of the nine donors who developed renal impairment required renal replacement therapy which was actually less than controls. The increased risk of ESRD in these donors may be related to some genetic predisposition especially as they were known family members.
Thus the increased incidence of ESRD in this study may be attributed to hereditary background rather than only nephrectomy.
The study limitations include that controls lived within one county, whereas donors were from various ones. The results can’t be applied to non- non-Caucasians. Strengths of the study mainly is the complete follow-up of both donors and controls with certified causes of death.
Further long-term studies with more appropriate controls are required to clearly evaluate the risks of renal donation.
They reached their conclusion by adopting larger numbers of both donors and recipients and longer follow up duration up to more than 20 years.
1. Please summarise this article in your own words
Living donation is the best treatment for ESRD , however it requires a healthy individual to undergo a surgery with no personal benefit to him/her rather it might harm him/her. As perioperative mortality in living donation is 0.2%. and in renal donation is 0.03%. in addition the donor had reduced renal function and hypertension which subsequently increase the cardiovascular risk and all cause mortality.
Though expected But this is not being proved, this might be attributed to the selection biased in the control groups. As mostly general population has been selected as a control group , including adults with medical conditions who are not suitable for kidney donation. More over the follow up period is around 6 yrs which is considered short for long term consequences to appear. There were cases reports of patient approached ESRD after kidney donations , but small in numbers.
Aim of the study to estimate long-term all -cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control group screened for eligibility for live-kidney donation.
Results
· Study population 2269 with live kidney donors at Oslo university hospital.
· Total 1901 after excluding marginal donors.
· 1519 1st degree relatives
· 89 were other relatives, 293 were unrelated.
· Median follow -up 15.1 (1.5-43.9) yrs.
· Mean eGFR at donation 104.7 ml/min per 1.73m2
· All donors were Caucasians.
· Controls were included from health study of Nord Trondelag (HUNT) population study. 32,621 were fitting the criteria and selected for the surveys.
· Median follow up for control group 24.9 (0.1-26)
· For donors outcome data on all cause mortality and RRT as curtained as of jan2010. CV mortality as Jan 2008.
· For control all out come data as curtained jan2010.
· During observation period: 224 death among donors , 68 (30.4) due to CV diseases.
· 2425 death among the control , 688 (28.4%) due to CV disease.
· The survival curve was significantly different with p<0.001.
· 9 donors (0.47%) developed ESRD , causes include GN, SLE , wegeners graulomatosis , ANCA positive vasculitis, Sarcoidosis, diabetes/ nephrosclerosois.
· In the control group 22 developed ESRD, causes include pyelonephritis, PKD, hypertension, diabetes , amyloidosis, SLE, drug induced nephropathy, medullary cystic disease and unknown.
· The estimated HR for ESRD in kidney donors was 11.38 (p<0.001)
Discussion:
Data shows increased in ESRD and CV diseases and all cause mortality during long term followup of kidney donors. This was observed after 5-10 yrs after donation.
The Author concluded That increased incidence of ESRD in the study cohort of kidney donors could be related to hereditary factors and not nephrectomy
Limitations of the study
· All controls lived within one county, whereas kidney donors were from all over Norway.
· no data on renal function in the control group was available.
· Longer follow-up time in controls may have influenced detection of ESRD cases.
· Due to missing data, could not adjust for the level of education.
The strength of the study is complete follow-up of all donors and controls with certified causes of death.
The findings raise some medical and ethical considerations regarding live-kidney donation. The present study indicates potential increased long-term risks for kidney failure and mortality in kidney donors
The author suggest potential donors should be informed of increased risks, although small, associated with donation in short-term and long-term perspective.
How did they reach this conclusion?
Due to long follow up of the donors and the control groups to compare.
Because the control were healthy similar to the donors who were selected and were eligible for donation because they were healthy.
Long-term risks for kidney donors
Living donor kidney transplantation is the preferred treatment for ESRD, because it is associated with improved graft and patient survival compared with transplantation from a deceased donor.
Perioperative mortality occur in 0.03% of kidney donors. Kidney donation
inevitably leads to reduced renal function and is associated
with an increase in proteinuria, as well as a rise in BP These factors are associated with an increased risk
for cardiovascular and all-cause mortality in the general population.
Follow-up studies of living organ donors have not reported increased cardiovascular and all-cause mortality,
but results may have been confounded by selection bias in the control groups.
The aim of this study: to examine the possible impact of living donor
nephrectomy within a longer follow-up time.
RESULTS
1901 donors were included live-kidney donations which were performed at Oslo University Hospital from 1963–2007.
Median follow-up time was 15.1 (1.5–43.9) years. Mean eGFR at donation was 104.7 ml/min per 1.73 m2. All donors were Caucasians.
Controls were included from the Health Study of Nord Trndelag (HUNT) population study. A control group of 32,621 was constructed to fit criteria for
kidney donation. Median follow-up time for the control group was 24.9 years.
There were 224 deaths among 1901 kidney donors, 68 (30.4%) of which were due to CVD. There were 2425 deaths among the 32,621 controls, 688
(28.4%) of which were due to CVD. No donors died during or immediately after the surgical procedure. A total of nine donors (0.47%) developed ESRD. All
were family members. Median time from donation
was 18.7 (10.3–24.3) years. Renal failure in donors was
mainly caused by immunological diseases. In the control group, 22
individuals developed ESRD.
DISCUSSION
This analysis demonstrated a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the
criteria for donation.
Living kidney donation is associated with a known
perioperative mortality risk and a small risk of major
complications related to the surgical intervention.
The causes of ESRD were different in donors and controls.
A likely explanation for the increased risk of ESRD in donors may be linked to
genetic factors, as the majority were immediate family
members.
Limitations of the study:
1. All controls lived within one county, whereas kidney donors were drawn from
all over Norway.
2. There were no data on renal function in the control group
3. Longer follow-up time in controls may have influenced detection of ESRD cases.
4. Due to missing data, they could not adjust for the level of
education (note: adjusting for level of education would most likely increase the risk estimates for donors).
5. They could not fully adjust for unmeasured confounders, for example, unknown comorbidities or differences in health-related behavior.
6. This results may be difficult to extrapolate to unrelated donors
and non-Caucasians.
The strength of the study:
1. Complete follow-up of all donors and controls with certified causes of death. 2. In the majority of patients, data were available regarding BMI, smoking, and BP, three major cardiovascular risk factors.
3. The longer follow-up time and the larger number of events.
Conclusion:
The findings of this study raise some medical and ethical considerations regarding live-kidney donation. The present study indicates potential increased long-term risks for kidney failure and mortality in kidney donors. However, this has to be put into perspective. However the findings will not change the opinion in promoting live-kidney donation.
The potential donors should be informed of increased risks associated with donation in short-term and long-term perspective.
An accepted ethical principle is that donors who are willing to donate may do so as long as they meet certain health criteria, have sufficient information about the
consequences of the donation process, and informed consent has been obtained. Therefore, any newly recognized risks should be implemented in donor information procedures.
Further long-term studies with appropriate controls are needed to fully judge the risks of kidney donation.
☆Long-term risks for kidney donors
▪︎Living donor kidney transplantation is the preferred treatment for ESRD, because it is associated with improved graft and patient survival compared with transplantation from a deceased donor.
▪︎Perioperative mortality occur in 0.03% of kidney donors. Kidney donation
inevitably leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in BP. These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population.
▪︎Follow-up studies of living organ donors have not reported increased cardiovascular and all-cause mortality, but results may have been confounded by selection bias in the
control groups.
▪︎The aim of this study: to examine the possible impact of living donor
nephrectomy within a longer follow-up time.
◇RESULTS
▪︎1901 donors were included live-kidney donations which were performed at Oslo University Hospital from 1963–2007.
▪︎Median follow-up time was 15.1 (1.5–43.9) years. Mean eGFR at donation was 104.7 ml/min per 1.73 m2. All donors were Caucasians.
▪︎Controls were included from the Health Study of Nord Trndelag (HUNT) population study. A control group of 32,621 was constructed to fit criteria for kidney donation. ▪︎Median follow-up time for the control group was 24.9 years.
▪︎There were 224 deaths among 1901 kidney donors, 68 (30.4%) of which were due to CVD. There were 2425 deaths among the 32,621 controls, 688 (28.4%) of which were due to CVD.
▪︎A total of nine donors (0.47%) developed ESRD. All were family members. ▪︎Median time from donation was 18.7 (10.3–24.3) years. Renal failure in donors was mainly caused by immunological diseases. In the control group, 22 individuals developed ESRD.
◇DISCUSSION
▪︎This analysis demonstrated a significant increase in ESRD, CVD, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the
criteria for donation.
▪︎Living kidney donation is associated with a known
perioperative mortality risk and a small risk of major
complications related to the surgical intervention.
The causes of ESRD were different in donors and controls.
▪︎A likely explanation for the increased risk of ESRD in donors may be linked to
genetic factors, as the majority were immediate family members.
Limitations of the study:
1. All controls lived within one county, whereas kidney donors were drawn from all over Norway.
2. There were no data on renal function in the control group
3. Longer follow-up time in controls may have influenced detection of ESRD cases.
4. Due to missing data, they could not adjust for the level of education.
5. They could not fully adjust for unmeasured confounders, for example, unknown comorbidities or differences in health-related behavior.
6. This results may be difficult to extrapolate to unrelated donors and non-Caucasians.
The strength of the study:
1. Complete follow-up of all donors and controls with certified causes of death. 2. In the majority of patients, data were available regarding BMI, smoking, and BP, three major cardiovascular risk factors.
3. The longer follow-up time and the larger number of events.
Conclusion:
▪︎The findings of this study raise some medical and ethical considerations regarding live-kidney donation.
▪︎The present study indicates potential increased long-term risks for kidney failure and mortality in kidney donors. This has to be put into perspective. However the findings will not change the opinion in promoting live-kidney donation.
▪︎The potential donors should be informed of increased risks associated with donation in short-term and long-term perspective.
▪︎An accepted ethical principle is that donors who are willing to donate may do so as long as they meet certain health criteria, have sufficient information about the consequences of the donation process, and informed consent has been obtained. Therefore, any newly recognized risks should be implemented in donor information procedures.
▪︎ Further long-term studies with appropriate controls are needed to fully judge the risks of kidney donation.
Living kidney donors are thought to preserve long-term renal function and experience no rise in cardiovascular or all-cause mortality, according to prior research.
However, the majority of investigations have had relatively little follow-up times and control groups that are less healthier than the community of living donors.
The study compared living kidney donors to a control group of people who would have been eligible for donation in terms of long-term renal function, cardiovascular disease, and overall mortality.
With a median follow-up of 15.1 years, researchers found that end-stage renal disease (ESRD), cardiovascular mortality, and all-cause mortality affected 1901 people who donated kidneys between 1963 and 2007.
With a median follow-up of 24.9 years, a control group of 32,621 possibly suitable kidney donors was chosen.
Comparing donors to controls, the hazard ratio for all-cause mortality was considerably elevated to 1.30 (95% confidence interval 1.11-1.52).
The risk of ESRD was considerably and significantly elevated to 11.38 (4.37–29.6), while the cardiovascular death rate increased significantly to 1.40 (1.03-1.91).
The prevalence of ESRD among donors was 302 instances per million, and genetic factors may have played a role in this.
The donors’ ESRD was brought on by immunological renal disease.
As a result, compared to a control group of non-donors who would have been eligible for donation, kidney donors have a higher long-term risk for ESRD, cardiovascular disease, and overall mortality.
The study reached this conclusion by choosing a control group of healthy individuals who are candidates for transplantation and long term follow up of a 24.9 years period.
Long-term risks for kidney donors
Q1- Please summarise this article in your own words
Although the Previous studies suggested that living kidney donors has no long-term renal and cardiovascular complication or all-cause mortality.
In this study Hazard ratio for all-cause death was significantly increased t for donors compared with control. There was a significant corresponding increase in cardiovascular death and ESRD risk .
The overall incidence of ESRD among donors was 302 cases per million. Immunological renal disease was the cause of ESRD in the donors.
Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group.
Living donor kidney transplantation is the preferred treatment with better outcome when Compared to a deceased donor.
perioperative mortality is about 0.03% of kidney donors.
Kidney donation is associated with reduced renal function ,
an increase in proteinuria and a rise in blood pressure (BP) greater than that of aging process .
same These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population.
Most previous Follow-up studies of living organ donors have not reported increased cardiovascular and all-cause mortality but these studies has bias in donor selection .
Three studies demonstrated no increase in cardiovascular disease or mortality over 6 years a follow-up .
It is possible, however, that living donors may be at increased risk of death after many years of donation.
Occurrence of ESRD in living donors has observed long term after kidney donation but the numbers are very low with statistical insufficiency .
This study demonstrated a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up compared to well selected control .
Living kidney donation is associated with perioperative mortality risk and a small risk of major complications related to the surgical intervention.
Garg et al. found no survival difference between kidney donors and a selected control group.
Segev et al. found that Donation was not associated with an increase in all-cause mortality. This study also observed no increase in all-cause mortality during the initial 5–10 years after donation, but thereafter thesurvival curves began to deviate .
In the general population, there is a association between reduced kidney function and mortality and premature vascular death. Several studies have reported that increased BP, albuminuria, and reduced renal function are associated with increased all-cause and cardiovascular mortality. These risk factors are more prevalent in kidney donors following nephrectomy.
Despite the inevitable reduction in renal function after nephrectomy, it appears that the medical community has not regarded loss of renal function in living kidney donors as a long-term risk factor for mortality and cardiovascular disease.
In this study, the donors had a substantially increased risk for developing ESRD compared with selected controls.
Seven out of the nine donors requiring renal replacement therapy had a primary
renal disease and this could be related to hereditary (or immunological ) factors and not only nephrectomy.
Although these findings should not not change our opinion in promoting live-kidney donation but potential donors should be informed of increased risks, although small, associated with donation in short-term and long-term perspective.
An accepted ethical principle is that donors who are willing to donate may do so
· as long as they meet certain health criteria,
· have sufficient information about the consequences of the donation process,
· and informed consent has been obtained.
Therefore, any newly recognized risks should be implemented in donor information procedures.
Q2- How did they reach this conclusion?
They reach to this conclusion by avoiding the bias that had been present in previous studies regarding the selection of control group (potentially eligible kidney donors) duration of follow up and statistically sufficient number of well selected control .
#Please summarise this article in your own words
* The aim of the present study was to estimate long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control group screened for eligibility for live-kidney donation.
# Introduction:
*Living donor kidney transplantation is the preferred treatment for (ESRD), because it is associated with improved graft and patient survival compared with transplantation from a deceased donor.
*Kidney donors are at increased long-term risk for ESRD, CVD, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.
*Perioperative mortality does occur during organ retrieval from living donors and have been estimated to occur in 0.2% of liver donors and 0.03% of kidney donors.
# RESULTS
* During 1963–2007, 2269 live-kidney donations were performed at Oslo University Hospital. 1901 donors were included. 1519 were first-degree relatives, 89 were other relatives, and 293 were unrelated. Median follow-up time was 15.1 years. Mean (eGFR) at donation was 104.7 ml/min per 1.73m2 . All donors were Caucasians.
*Controls were included from the (HUNT) population study. Out of the 74,991 individuals participating in this population-based survey, a control group of 32,621 was constructed to fit criteria for kidney donation. Median follow-up time for the control group was 24.9 years.
*There were 224 deaths, (30.4%) due to CVD among study group. There were 2425 deaths among the controls, (28.4%) of which were due to CVD.
* No donors died during or immediately after the surgical procedure.
* The survival curves were significantly different.
*The unadjusted risk associated with kidney donation was 95%. In adjusted complete case analysis, the HR for kidney donors was 1.48.
* After multiple imputation, HR was 1.30. There was a corresponding increase in cardiovascular mortality (HR 1.40)
*A total of nine donors (0.47%) developed ESRD. All were family members. Median time from donation was 18.7 years.
* Renal failure in donors was mainly caused by immunological diseases: GN (N=3), SLE (N=1), Wegener’s granulomatosis (N=1), ANCA-positive vasculitis (N=1) , sarcoidosis (N=1) , and diabetes/nephrosclerosis (N=2).
* In the control group, 22 individuals developed ESRD. Reported causes were glomerulonephritis (n=5), pyelonephritis (n=4), polycystic kidney disease (n=4), hypertension (n=3), diabetes (n=1),
amyloidosis (n=1), systemic lupus erythematosus (n=1), drug induced nephropathy (n=1), medullary cystic disease (n=1), and unknown (n=1).
*The crude incidence of ESRD in donors was 302 per million person-years. The overall incidence rate for development of ESRD in Norway is about 100 per million per person-year.
#The strength of our study:
Complete follow-up of all donors and controls with certified causes of death. In themajority of patients, data were available regarding BMI, smoking, and BP, three major cardiovascular risk factors. The longer follow-up time and the larger number of events.
#The limitation of study all kidney transplantations are performed at a single center
# How did they reach this conclusion?
*They compared long-term renal function and cardiovascular and all-cause mortality in living
kidney donors compared with a control group of individuals who would have been eligible for donation.
*All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years.
According to literature and this article there is very low risk of renal disease after nephrectomy, however, it was seen than seven of nine LRD has developed ESRD they(LRD) may have some underlaying disease.
Donors are at higher risk of developing some comorbid like hypertension secondary to hyperfiltration, CVD etc.
Also metanalysis shows control group are less healthy then LRD.
They have followed the LRD group for 15 years and found that there is significant increase risk of all cause death up to 1.5% of control group, in this article it was observed that the overall incidence of ESRD was 302 per million.
☆Long-term risks for kidney donors
▪︎Living donor kidney transplantation is the preferred treatment for ESRD, because it is associated with improved graft and patient survival compared with transplantation from a deceased donor.
▪︎Perioperative mortality occur in 0.03% of kidney donors. Kidney donation
inevitably leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in BP These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population.
▪︎Follow-up studies of living organ donors have not reported increased cardiovascular and all-cause mortality, but results may have been confounded by selection bias in the
control groups.
▪︎The aim of this study: to examine the possible impact of living donor
nephrectomy within a longer follow-up time.
¤RESULTS
▪︎1901 donors were included live-kidney donations which were performed at Oslo University Hospital from 1963–2007.
▪︎Median follow-up time was 15.1 (1.5–43.9) years. Mean eGFR at donation was 104.7 ml/min per 1.73 m2. All donors were Caucasians.
▪︎Controls were included from the Health Study of Nord Trndelag (HUNT) population study. A control group of 32,621 was constructed to fit criteria for kidney donation. ▪︎Median follow-up time for the control group was 24.9 years.
▪︎There were 224 deaths among 1901 kidney donors, 68 (30.4%) of which were due to CVD. ▪︎There were 2425 deaths among the 32,621 controls, 688 (28.4%) of which were due to CVD. No donors died during or immediately after the surgical procedure. A total of nine donors (0.47%) developed ESRD. Allwere family members. ▪︎Median time from donationwas 18.7 (10.3–24.3) years. Renal failure in donors was mainly caused by immunological diseases. In the control group, 22 individuals developed ESRD.
¤DISCUSSION
▪︎This analysis demonstrated a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the
criteria for donation.
▪︎Living kidney donation is associated with a known
perioperative mortality risk and a small risk of major
complications related to the surgical intervention.
▪︎The causes of ESRD were different in donors and controls.
¤ Limitations of the study:
1. All controls lived within one county, whereas kidney donors were drawn from
all over Norway.
2. There were no data on renal function in the control group
3. Longer follow-up time in controls may have influenced detection of ESRD cases.
4. Due to missing data, they could not adjust for the level of education (note: adjusting for level of education would most likely increase the risk estimates for donors).
5. They could not fully adjust for unmeasured confounders, for example, unknown comorbidities or differences in health-related behavior.
6. This results may be difficult to extrapolate to unrelated donors
and non-Caucasians.
¤ Strength of the study:
1. Complete follow-up of all donors and controls with certified causes of death. 2. In the majority of pts, data were available regarding BMI, smoking, and BP, and the major cardiovascular risk factors.
3. The longer follow-up time and the larger number of events.
¤ Conclusion:
▪︎The findings of this study raise some medical and ethical considerations regarding live-kidney donation.
▪︎The present study indicates potential increased long-term risks for kidney failure and mortality in kidney donors. However the findings will not change the opinion in promoting live-kidney donation.
▪︎The potential donors should be informed of increased risks associated with donation in short-term and long-term perspective.
▪︎An accepted ethical principle is that donors who are willing to donate may do so as long as they meet certain health criteria, have sufficient information about the consequences of the donation process, and informed consent has been obtained. Therefore, any newly recognized risks should be implemented in donor information procedures.
▪︎Further long-term studies with appropriate controls are needed to fully judge the risks of kidney donation.
▪︎The findings will not change the opinion in promoting live-kidney donation.
▪︎The potential donors should be informed of increased risks associated with donation in short-term and long-term perspective.
▪︎An accepted ethical principle is that donors who are willing to donate may do so as long as they meet certain health criteria, have sufficient information about the consequences of the donation process, and informed consent has been obtained. Therefore, any newly recognized risks should be implemented in donor information procedures.
▪︎Further long-term studies with appropriate controls are needed to fully judge the risks of kidney donation.
Summary:
Previous studies have suggested that living kidney donors maintain long-term renal function and experience no increase in cardiovascular or all-cause mortality.
In this study they compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation.
All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years.
A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years. Hazard ratio for all-cause death was significantly increased to 1.30 (95% confidence interval 1.11–1.52) for donors compared with controls.
There was a significant corresponding increase in cardiovascular death to 1.40 (1.03–1.91), while the risk of ESRD was greatly and significantly increased to 11.38 (4.37–29.6). The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors.
Immunological renal disease was the cause of ESRD in the donors. Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.
How did they reach this conclusion?
1. Avoid selection bias.
2. Control group were carefully selected as healthy individuals
3. Long term follow up duration of median follow-up time of 24.9 years.
This study compared long term renal function, cardiovascular and all-cause mortality in living kidney donors with a control group of people who would have been eligible for donation whereas previous studies had considered control groups of individuals who were less healthy than the living donors and a shorter follow up period. According to the previous studies living kidney donors maintained long term renal function and did not have an increased cardiovascular and all-cause mortality.
This analysis showed that there is a remarkable increase in ESRD, cardiovascular and all-cause mortality in long term follow up of living kidney donors compared with a control group of individuals who had been selected with similar criteria to the living donors (without coexisting medical conditions such as diabetes, hypertension, cardiovascular disease)
A follow up of 15.1 years of 1901 living kidney donors between 1963 and 2007 showed all-cause mortality, cardiovascular mortality and ESRD. A control group of 32621 individuals who could have been potential kidney donors were considered with a follow up of 24.9 years. In donors there was an increase of all-cause death of 1.30 compared with the control group, an increase in cardiovascular death to 1.4 and a significant increase of ESRD to 11.38. The explanation for increased ESRD in donors could be mostly due to hereditary factors, as most of the donors were family members, and not only to nephrectomy. Following nephrectomy donors experience Reduced kidney function which is associated to cardiovascular and premature vascular death.
A potential increase in long term risk for kidney failure and mortality in kidney donors should be highlighted to potential kidney donors.
Please summarise this article in your own words
Numerous studies were conducted to assess the impact of nephrectomy on kidney transplant living donors (KLD) . Most results were under estimating possible impact of living donor nephrectomy either because of selection bias and the choose of control groups with health issues in comparison to KLD, or because of a short term follow up duration .
This study was designed to evaluate post donation mortality and complications over a long follow up duration. Estimation was done for all cause mortality, cardiovascular mortality and risk for ESRD.
case group study was designed, 1901 living donors were included and a control group of 32,621 healthy individual that would fit criteria for kidney donation . follow up of both groups was done over a long followup duration period from 1963 to 2007.
During the follow up period, there were 224 deaths among 1901 kidney donors due to cardiovascular disease , 2425 deaths among the 32,621 controls, 688 (28.4%) of which were due to cardiovascular disease. No donors died during or immediately after the surgical procedure
Analysis of the results showed a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the criteria for donation.
ESRD among donors was influenced by hereditary factors and was mainly due to immunological renal diseases.
Finally , the Study concluded that living kidney donation is associated with increased risk of kidney failure and mortality.
How did they reach this conclusion?
1) They avoided selection bias , donors were selected according to the general guidelines of donor selection , and exclusion of marginal donors.
2) Control group were carefully selected as healthy individuals with no underlying comorbid condition that would be accepted as a potential donor as cardiovascular disease, malignancy, diabetes, hypertension, and chronic kidney
3) Long term follow up duration of median follow-up time of 24.9 years.
complete follow-up of all donors and controls with certified causes of death., data were available regarding BMI, smoking, and BP, three major cardiovascular risk factors
LKD leads to
· reduced renal function
· increased BP
· increased proteinuria,
associated with increased cardiovascular and all-cause mortality in general population.
LKD have been shown to maintain renal function over long-term without any increase in cardiovascular or all-cause mortality in previous studies published.
The drawback of these studies was that the control group was general population and they were of short-duration follow-up (upto 6 years).
This is a retrospective study was done involving 1901 renal donors from 1963 to 2007, comparing them with 32,621 healthy individuals (who could be potential donors) with respect to cardiovascular and all-cause mortality and risk of ESRD.
The median follow-up in the study was also long-term (15.1 years for the donors and 24.9 years for the control population).
There was increased all-cause mortality,30% and cardiovascular death, 40% compared to the control group, but deviation in the survival graph happened only after 5-10 years of donation . The risk of ESRD in the donor group was 11.38 times more than the control population, mostly due to immunological causes.
The limitations of the study include:
· all the controls were from same county,
· donors were from different areas
· no data available for the renal function in the control group
· the follow-up time in the controls was longer than the donor group
· the population included Caucasians and the donors were related to the recipients, hence extrapolation to non-Caucasians and unrelated donors is not possible.
The strengths of the study include
· complete follow-up a
· s certified causes of death
So, the study pointed showed long-term risks to potential kidney donors with regards mortality and development of ESRD.
How did they reach this conclusion?
the donors had a substantially increased risk for developing ESRD compared with selected controls. The causes of ESRD were different in donors and controls. Seven out of the nine donors requiring renal replacement therapy had a primary renal disease. This was less common in controls. A likely explanation for the increased risk in donors may be linked to genetic factors, as the majority were immediate family members.
Previous studies have suggested that living kidney donors maintain long-term renal function and experience no increase in cardiovascular or all-cause mortality.
However, most analyses have included control groups less healthy than the living donor population and have had relatively short follow-up periods.
Aim of the study:
To compare the long-term renal function and cardiovascular and all-cause mortality in living kidney donors with a control group of individuals who would have been eligible for donation.
Methods:
inclusion criteria: donors who are selected according to the standard guidelines.
Exclusion criteria: antihypertensive medication, BP4140/90 mm Hg, BMI>30 kg/m2, >70 years or <20 years of age, macroalbuminuria, or eGFR <70 ml/min per 1.73 m.
To achieve appropriate controls for kidney donors, only subjects with BP<140/ 90 mm Hg and BMI<30 kg/m2 were included. Furthermore, only those who rated their own health as ‘good’ or ‘excellent’ were selected. Individuals with diabetes, cardiovascular disease, or using BP-lowering medication were excluded.
Results:
All-cause mortality, cardiovascular mortality, and end-stage renal disease were identified in 1901 individuals who donated a kidney from 1963 through 2007 with a median follow-up of 15.1 years.
A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years.
The hazard ratio for all-cause death was significantly increased to 1.30 for donors compared with controls.
There was a significant corresponding increase in cardiovascular death to 1.40.
The risk of ESRD was greatly and significantly increased to 11.38.
The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors.
Immunological renal disease was the cause of ESRD in the donors.
Conclusion:
kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.
Please summarize this article in your own words
This study aims to assess short and long-term all-cause mortality, risk of ESRD and cardiovascular mortality in kidney donors compared to a group screened for eligibility for live-kidney donation as controls.
1901 Donors and 32,621 controls fulfilling standard donation criteria were included during 1963-2007 at University Hospital in Norway.
Median follow up time of Donor and controls were 15 years and 25 years respectively.
Mean eGFR at donation was 104 ml/min and all were Caucasians.
Hazard ratio after multiple imputations for Death, Cardiovascular mortality, and risk of ESRD in kidney donors compared to controls was found to be 1.3,1.4 and 11.3 respectively.
This study demonstrated that during long term follow-up, a significant increase in risk of ESRD, all-cause and cardiovascular mortality in kidney donors as compared to selected control population who have met criteria for kidney donation.
In most of previous studies, donation was not found to have an increased risk to donors due to unselected population and prevalence of raised BP, albuminuria and reduced renal function in general unselected population when included as controls.
Limitations: Donor were favored in terms of close follow up schedule and level of education as all belong to one county with better literacy compared to selected controls which hails from all over Norway. Results of the study are difficult to extrapolate to non-Caucasians and non-related donors.
Strength: Raises medical and ethical issues in consideration for living kidney donation. Donors should have sufficient information and well-informed concerning short- and long-term risks of donation (though small) and informed consent has to be obtained.
How did they reach this conclusion?
Most previous studies which compared long term risk for donors have two caveats:
1. They analyzed general population as control group, which are less healthy compared to living donor population and found no increase in ESRD, all risk and Cardiovascular mortality
2. Periods of follow were relatively short, so not able to detect any difference between donors and control group during long term
Summary
This study is about long term risks of kidney donors. In order to be sufficiently accurate, this study has included control groups that are also eligible for donation. This evens out the 2 groups and allows us to get to a more accurate result. Longer follow up has also be done in comparison with previous studies surrounding the same topic.
The study found that kidney donors have an increased risk of cardiovascular events and death along with significantly increased risk of ESRD. However, hereditary factors may play a role in incidence of ESRD in donors. All cause mortality risk is also increased in donors.
In order to assess risk of cardiovascular death, the study included important risk parameters for the participants such as BP, BMI and smoking. Longer follow up has helped in coming to the above conclusion of increased risk.
Living kidney donors have surgical risks in the short term such as perioperative mortality risk.
Lifestyle modifications such as smoking abstinence, regular exercise, good diet with low sodium intake, modest or nil alcohol consumption, and having blood pressure and blood glucose levels under control are to be undertaken by the donor and maintained in the long term.
In view of the above risks, donors are only allowed to donate after they have met the health criteria required to be a kidney donor, and have understood the risks involved in the process, as well as the important lifestyle modifications they would have to maintain life long. If all these are met, then the patient is asked to give informed consent to donate.
How the study reached its conclusion :
This study has reached this conclusion through 2 major approaches :
Summary
Renal donation is associated with reduced kidney function, rise of BP and increase in proteinuria, leading to increased cardiovascular and all-cause mortality in general population. Living kidney donation have been shown long term maintenance of renal function without increase in cardiovascular or all-cause mortality in previous studies. The drawback of these studies was having control group selected from general population and they were of short-duration follow-up.
A retrospective study was done, comparing donors healthy individuals ;who could be potential donors, with respect to cardiovascular and all-cause mortality and risk of ESRD. The median follow-up in the study was also long-term.
There was30% increase in all-cause mortality and 40% increase in cardiovascular death in the donor group as compared with control group, with divergence of survival graph after first 5-10 years. Risk of ESRD in the donor group was 11.38 times more than the control population. mostly associated with immunological issues..
Study limitations include that controls were selected from same county, while donors were selected from different areas; no data available for the renal function regarding control group; follow up time in the controls was longer than the donor group; the population included Caucasians and the donors were related to the recipients, so, extrapolation to non-Caucasians and unrelated donors is not possible. Strength points of the study involve enough follow up & certified death causes.
The study showed increased long-term risks to potential kidney donation regarding mortality and development of ESRD.
How reaching conclusion:
Through removing selection bias from the study and longer follow up period, as survival graph diverged in the 2 groups 5-10 years after donation.
Disadvantage of general population selection is that it may include those with medical disorders making them less comparable with the donors with thorough medical evaluation leading to selection bias
Long-term risks for kidney donors
· Perioperative mortality occurs in 0.2% of liver donors and 0.03% of kidney donors.
· Less serious perioperative risks are accepted and well documented
· Kidney donation leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in blood pressure (BP)
· These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population.
The aim of the present study: to estimate long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control group screened for eligibility for live-kidney donation
RESULTS
1901 donors were included (1519 first-degree relatives, 89 other relatives, and 293 unrelated).
Median follow-up time was 15.1 (1.5–43.9) years.
Mean estimated glomerular filtration rate (eGFR) at donation was 104.7 ml/min per 1.73 m2 (n ¼ 1766,
All donors were Caucasians
Exclusion criteria for population-based survey:
· Age>70 and <20 years
· BMI>30 and <17 kg/m2
· BP>140/90 mm Hg
· BP medication
· Diabetes
· CVD
· Reduced general health
Exclusion criteria for kidney donors in Norway 1963–2007
· Age>70 and <20 years
· BMI>30 and <17 kg/m2
· BP>140/90 mm Hg
· BP medication
· eGFR < 70 ml/min per 1.73 m2
1901 Donors and 32,621 controls fulfilled standard donation criteria
Conclusion
· There was a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation
· Living kidney donation is associated with a known perioperative mortality risk and a small risk of major complications related to the surgical intervention
limitations of the study:
1. All controls from one county, while kidney donors were drawn from all over Norway
2. renal function in the control group not estimated
3. Longer follow-up time in controls could have a role in detection of ESRD cases
4. Education level was not the same between Norwegian donors and controls
The strength of the study
1. complete follow-up of all donors and controls with certified causes of death
2. Documented data for most of patients
3. Longer follow up time than other studies and larger number of events
Ethical issues:
· Donor should meet certain health criteria for eligibility for donation
· Donor should have enough information about the consequences of the donation process, and informed consent has been obtained
· Any newly recognized risks should be implemented in donor information procedures
MATERIALS AND METHODS
· Stata version 11SE used in Statistical analyses.
· Parametric and non-parametric tests were chosen as appropriate for descriptive comparisons.
· Cox regression was used to investigate the outcomes of all-cause mortality, cardiovascular mortality, and renal replacement therapy.
· The proportional hazards assumption was tested using observed versus expected plots and Schoenfeld residuals.
How did they reach this conclusion
· They completed follow up of all donors and controls with certified causes of death
· Documented data
· Longer follow up time and the larger number of events
· The exclusion criteria for controls was the same as for donation
. Long-term risks for kidney donors
This is one of the key articles that changed our understanding of the risk of donation.
The article is about living donation as the best treatment option for patients with ESRD and has the best survival rate for the graft and patients than the donor. This article helps to compare long-term causes of mortality, CV mortality, and the risk for ESRD in kidney donors with a selected group control from the population that fulfills the criteria for renal or kidney donation.
The study was very interesting and was conducted in Oslo University Hospital, Oslo, Norway. The study started from 1963 to 2007 with a total of 1901 donors with a follow-up median of about 15.1 years. Based on the study, they excluded the following:
Exclusion criteria:
1) HTN on Medications
2) BP 140/90
3) BMI OF 30 kg/m2- obese donors
4) Greater than 70 years and less than 20 years
5) Macroalbuminuria
6) A GFR of less than 70 ml/min
Inclusion criteria:
Are only donors who were selected according to the standard guidelines.
The control group had the following inclusion criteria:
1) Age 20 or more
2) BP less than 140/90
3) BMI less than 30 kg/m2
Exclusion criteria:
Patients with DM, HTN with medications, and CVD.
The study was compared with another group of potential donors of a population of about 32621 with a median follow-up of 24.9 years with no comorbidities like HTN, DM, obesity, etc.
The conclusion of the study found that patients who are kidney donors have an increased risk of cardiovascular disease, ESRD, and all-cause mortality than those other populations that are the control group who are non-donors but were possibly eligible for donations.
They arrived at this conclusion by comparing long-term renal function and CV and all-cause mortality in living kidney donors with a control group that would be eligible for donation but did not do any transplantation. The risk factors are found more frequently in donors following nephrectomy. Now since that is an issue, it must show concern for the possibility of having an increase in cardiovascular disease with increased mortality and morbidity.
– Living donor kidney transplantation is the preferred treatment for end-stage renal disease (ESRD), because it is associated with improved graft and patient survival compared with transplantation from a deceased donors .
– Although rare, perioperative mortality does occur during organ retrieval from living donors and have been estimated to occur in 0.2% of liver donors and 0.03% of kidney donors. Less serious perioperative risks are accepted and well documented . Kidney donation inevitably leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in blood pressure (BP) greater than that attributable to normal aging. These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population .
– Follow-up studies of living organ donors have not reported increased cardiovascular and all-cause mortality, but results may have been confounded by selection bias in the control groups
– In most studies, controls were selected from the general population, which includes adults with medical conditions that would make them ineligible for kidney donation. As a result, these controls would have been less healthy than the living donors and an effect of organ donation on all-cause and cardiovascular mortality could have been underestimated.
– The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors. Immunological renal disease was the cause of ESRD in the donors. Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation
– The aim of this study is to estimate long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control group screened for eligibility for live-kidney donation .
– This study is changing the practice in comparing the long term outcome of transplantation by comparing the donors with very healthy population instead of using the control group as less healthy as in previous studies .
– Here they compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation .
>>Exclusion criteria in the donors( n= 1901) :
– age>70 years (n =89)
– age<20 years (n =6)
– BMI>30 kg/m2 (n =125)
– BMI<17 kg/m2 (n =1)
– BP>140/90 mm Hg(n =98)
– BP medication (n =8)
– eGFR < 70 ml/min per1.73 m2 (n =41)
>>exclusion criteria for the control group(n= 32,621 ) :
– age>70 years (n =12,745)
– Age<20 years (n =24)
– BMI>30 kg/m2(n =1998)
– BMI<17 kg/m2 (n =23)
– BP>140/90 mm Hg(n =8964)
– BP medication (n =4991)
– Diabetes (n =1348)
– CVD (n =2765)
– Reduced general health(n =9512)
– The analysis demonstrated a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the criteria for donation.
– these findings raise some medical and ethical considerations regarding live-kidney donation. The present study indicates potential increased long-term risks for kidney failure and mortality in kidney donors. However, this has to be put into perspective .
– Our findings will not change our opinion in promoting live-kidney donation. However, potential donors should be informed of increased risks, although small, associated with donation in short-term and long-term perspective .
This is a single-center study (including the only transplant hospital in the country) which facilitates the quality of the data involved as well as the follow-up for an extended period of time. It even avoids a control group selection bias, where studies usually compare with the general population instead of comparing with the population with the same clinical criteria as the potential donor group.
While most studies use a follow-up of six years on average, they were able to note that from ten years after transplantation the groups had different evolution of renal filtration, increasing cardiovascular mortality (HR 1.4).
The study showed increased loss of renal and cardiovascular function and long-term all-cause mortality. Nephrectomy associated or not with hereditary factors may be one of the causes for these data in this specific study.
30 to 40% of patients were living donors, since 1995 accepting close friends and not just family.
Kidney donation leads to reduced renal function, increased BP and increased proteinuria, which are associated with increased cardiovascular and all-cause mortality in general population. Living kidney donors have been shown to maintain renal function over long-term without any increase in cardiovascular or all-cause mortality in previous studies published. The drawback of these studies was that the control group was general population and they were of short-duration follow-up (upto 6 years).
With these issues in mind, a retrospective study was done involving 1901 renal donors from 1963 to 2007, comparing them with 32,621 healthy individuals (who could be potential donors) with respect to cardiovascular and all-cause mortality and risk of ESRD. The median follow-up in the study was also long-term (15.1 years for the donors and 24.9 years for the control population).
There was increased all-cause mortality (by 30%) and cardiovascular death (by 40%) in the donor group as compared to the control group, but the divergence in the survival graph happened only after first 5-10 years. The risk of ESRD in the donor group was 11.38 times more than the control population, but mostly due to immunological causes.
The limitations of the study include: all the controls were from same county, while the donors were from different areas; no data available for the renal function in the control group; the follow-up time in the controls was longer than the donor group; the population included Caucasians and the donors were related to the recipients, hence extrapolation to non-Caucasians and unrelated donors is not possible. The strengths of the study include: complete follow-up as well as certified causes of death
So, the study pointed towards increased long-term risks to potential kidney donors with respect to mortality and development of ESRD.
The conclusion was reached by removing the selection bias from their study: They used healthy potential donors as the control group. Secondly, a longer follow-up period was able to show the difference in mortality rates, as the survival graph diverged in the 2 groups a decade after donation.
They compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation.
There was a significant corresponding increase in cardiovascular death to
1.40 (1.03–1.91), while the risk of ESRD was greatly and significantly increased to 11.38 (4.37–29.6). The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors. Immunological renal disease was the cause of ESRD in the donors. Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.
Kidney donation inevitably leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in blood pressure (BP) greater than that attributable to normal aging. These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population.
The aim of the present study was to estimate long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control group screened for eligibility for live-kidney donation.
As a result, concerns have been expressed that kidney donation could lead to increased cardiovascular morbidity and mortality. Despite the inevitable reduction in renal function after nephrectomy, and evidence from the general population, it appears that the medical community has not regarded loss of renal function in living kidney donors as a long-term risk factor for mortality and cardiovascular disease.
The present study indicates potential increased long-term risks for kidney failure and mortality in kidney donors.
———————-
All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years. Hazard ratio for all-cause death was significantly increased to 1.30 (95% confidence interval
1.11–1.52) for donors compared with controls.All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years. Hazard ratio for all-cause death was significantly increased to 1.30 (95% confidence interval1.11–1.52) for donors compared with controls.
The analysis demonstrated a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term
follow-up after living kidney donation compared with a selected population of non-donors who would have met the criteria for donation.
In the present analysis, these marginal donors were excluded; only donors who were selected according to the standard guidelines were included in the study. Exclusion criteria were: antihypertensive medication, BP4140/90mmHg, BMI430 kg/m2 , 470 years or o20 years of age, macroalbuminuria, or eGFR o70 ml/min per 1.73 m 2
To achieve appropriate controls for kidney donors, only subjects with BPp140/ 90 mm Hg and BMIp30 kg/m 2 were included. Furthermore, only those who rated their own health as ‘good’ or ‘excellent’ were selected. Individuals with diabetes, cardiovascular disease, or using BP-lowering medication were excluded
Cox regression was used to investigate the outcomes of all-cause mortality, cardiovascular mortality, and renal replacement therapy.
Living donation is the treatment of choice for ESRD patient because it has better survival rate for the graft and patient than deceased donor.
the aim of this article is to compare long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors with a selected control group of population they fulfill the criteria for donation .
The study area was in one center (Oslo University Hospital, Oslo, Norway)
they study 1901 donors who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years.and exclude the following
1- HTN on medication
2-BP > 140/90 .
3- obese donor with BMI > 30 kg/m 2 .
4- > 70 years or< 20 years of age .
5- macroalbuminuria .
6- eGFR < 70 ml/min per 1.73 m 2 .
comparing them with 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years which not have co morbidity such as HTN , obesity etc ..
The result ;
kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been
eligible for donation.
Limitations of this study is all controls live in one country whereas kidney donors were from all over Norway.
They compared long-term renal function & CV & all-cause mortality in living kidney donors with a control group of individuals who would have been eligible for donation.
All-cause mortality, CV mortality, & ESRD was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years.
A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years
Long term risks for kidney Donors
Historically studies have suggested that living renal donors do not lose kidney function and there is no increased cardiovascular risk or all cause mortality. However the limitation of those analysis was that they included the control group which was less healthy than living donor population and there was short follow up.
In this study, long term renal functions and cardiovascular and all cause mortality in living donors was compared with control group who was possibly quite eligible for kidney donation
Total donors were 1901
Between 1963-2007
Median follow up 15.1 years
Control group – 32621 potential donors
Data Analysis-
Start Version 1 ISE, Cox regression analysis, parametric and non parameric tests.
Analysis method- Multi variate analysis
Findings
Hazard ratio for all cause death was 1.3 (95% Confidence innterval) for donors compared with controls.
Increased cardiovascular deaths of HR 1.4
Risk of ESRD was increased to 11.38
Over all incidence of ESRD was 302 cases per million
It might have been influenced by hereditary factors
Immunological renal disease was cause of ESRD iin donors
Conclusion–
Kidney donors have increased risk of ESRD in long term
They have high risk of all cause mortality and cardiovascular disease when compared to control group of non donors who would have been eligible for donation
Limitations
Donors and controls were different areas of Norway
Strength
Long follow up period
Please summarise this article in your own words
This study from Norway assessed long-term risks for kidney donors. They compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation. Previous studies were using the general population as a control group and therefore no survival difference was found. Three studies have been published with appropriate controls but with a mean follow up of around 6 years and demonstrated similar findings with no survival difference between donors and controls.
In this study by Mjen et al. all-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years.
Results: Hazard ratio for all-cause death was significantly increased to 1.30 for donors compared with controls. There was a significant corresponding increase in cardiovascular death to 1.40, while the risk of ESRD was greatly and significantly increased to 11.38.
The increased incidence of ESRD in this cohort of kidney donors could be related to hereditary factors and not only nephrectomy as most of the causes were related to immunological renal disease.
This study showed that kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.
How did they reach this conclusion?
This study showed that kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation. This could be due to the selection criteria for the control group, the longer follow-up time and the larger number of events.
Living donor transplantation has been a necessity and essential part of providing patients with ESRD freedom from dialysis and giving the transplanted patients a superior quality of life. Most potential living donors are willing to accept a degree of risk when the recipient is a family member or a close friend.
The findings of this stud will not change the author’s opinion in promoting live-kidney donation. However, potential donors should be informed of increased risks, although small, associated with donation in short-term and long-term perspective.
What is the disadvantage of using the general population as a control group?
Most published studies have used unselected general populations as the control group skewing results in favor of the donor cohorts as controls with coexisting medical conditions such as cardiovascular disease, malignancy, diabetes, hypertension, and chronic kidney disease were included that would have made them ineligible for kidney donation.
Lin et al. demonstrated that applying donor health criteria to an unselected population would yield a group with a lower mortality rate. Such a group would clearly be more relevant for mortality comparisons with living donors. Therefore bias issues would be a concern.
The aim of the study ;
The aim of the present study was to estimate long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control group screened for eligibility for live-kidney donation.
The study area ;
at a single center (Oslo University Hospital, Oslo, Norway) .
The type o study ;
Cohort study
The population ;
1-Donors;
1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years.
Inclusion criteria;
only donors who were selected according to the standard guidelines were included in the study.
Exclusion criteria were:
1-antihypertensive medication.
2-BP more than 140/90 mm Hg .
3- BMI more than30 kg/m 2 .
4- more than 70 years or less 20 years of age .
5- macroalbuminuria .
6- eGFR70 ml/min per 1.73 m 2 .
The control group ;
A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years.
Inclusion criteria;
1- age 20 years or more .
2- BP less 140/90 .
3- BMI less than kg/m 2 .
Exclusion criteria ;
Individuals with diabetes, cardiovascular disease, or using BP-lowering medication were excluded.
The method ;
A more comprehensive description of the survey is available at the HUNT study’s website (http://www.medisin.ntnu.no/hunt/).
Statistical analyses;
1- using Stata version 11SE (StataCorp, 4905, StataCorp, College Station, TX).
2-Parametric and non-parametric tests were chosen as appropriate for descriptive comparisons.
3-Cox regression was used to investigate the outcomes of all-cause mortality, cardiovascular mortality, and renal replacement therapy.
4-The proportional hazards assumption was tested using observed versus expected plots and Schoenfeld residuals.
5-Survival analyses were adjusted for age, gender, year of inclusion (donation), systolic BP, smoking status, and BMI
.
The result ;
kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been
eligible for donation.
The strength of the study ;
1-is complete follow-up of all donors and controls with certified causes of death.
2- In the majority of patients, data were available regarding BMI, smoking, and BP, three major cardiovascular risk factors.
The limitations of the study ;
1-All controls lived within one county, whereas kidney donors were drawn from all over Norway.
2- no data on renal function in the control group .
3-The study was not fully adjusted for unmeasured confounders, for example, unknown co morbidities or differences in health-related behavior.
How did they reach this conclusion?
1- In the general population ,several studies have reported that increased BP, albuminuria, and reduced renal function are associated with increased all-cause and cardiovascular mortality.
2-These risk factors are more prevalent in kidney donors following nephrectomy. As a result, concerns have been expressed that kidney donation could lead to increased cardiovascular morbidity and mortality.
Depend on the evidence from the general population and the inevitable reduction in renal function following nephrectomy .
Summary of the study:
Its a landmark prospective study to verify the long-term complications post donation.
The long term complication tested include:
1-All cause mortality
2-Cardiovascular mortality.
3- ESKD.
The control group was selected cohort from general population of those who are eligible for donation as per the current criteria for selection of donors, criteria include of election include:
Blood pressure below 140/90.
Non-diabetic.
No cardiovascular disease.
BMI below 30
Not on anti-hypertensive medications
No. of people in control group 32621.
No. of included donors 1901, Only the donors who fulfil the criteria for donation were selected,
exclusion criteria for donors:
was GFR below 70 ml/min,
BMI more than 30 ,
age more than 70 or below 20,
on anti-hypertnsive medication. which is similar to the criteria applied for control group selection.
Median follow up duration 15.1 years.conducted from 1963 to 2007
Median GFR at time of donation was 104 ml/min.
All of them were cauasians,
Results:
All-cause mortality was significantly increased to the ratio 0f 1.3
cardiovascular mortality 1.4
ESKD 11.38.
The causes of ESRD are immunologically mediated renal disease including SLE, Vasculitis, primary glomerular disease.
This study was showing different outcome from the previous studies because of the different stringent criteria they applied to select the control group which was synonymous to the criteria of suitable donors.
Take home message from this study is that Kidney donation is not increasing the risk for ESKD as the immunologically mediated diseases were the underscored culprits, rather than causes related to nephrons deficiency inflicted by donation. That discrepancy in the incidence of immunologic disease related-ESKD might be explained by higher rate of related donation.
Furthermore, the higher incidence of ESKD might explain the soaring incidence of all-cause and cardiovascular mortality.
Please summarise this article in your own words.
The living donor kidney transplantation is better for the recipients survival and graft survival than cadaveric kidney transplant.
This study conducted in Norway comparing kidney donors to controls fulfill the criteria for donation, unlike other previous studies comparing kidney donor to population may be fit or not fit for donation.
Design: Comparing all kidney transplantation in one center in Oslo/Norway since 1963 till 2007, to potential donor in all Norway according to local guidelines.
Exclusion criteria :B/P > 140/90, BMI > 30 kg/m2, > 70 nad < 20 years of age, macroalbuminuria and eGFR epi <70 ml/min/1.7m2,, DM , HTN on antihypertensive medications, and cardiovascular disease.
The result = there was an increased risk of developing ESRD most of then due to immune diseases, increased risk of all cause mortality and cardiovascular mortality in kidney donors in comparison to control.
there is a 3 fold increase in incidence of ESRD in donors compared to general population in Norway(302/million- 100/million).
Conclusion: kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.
limitations: The donors were form one country will control were from all Norway.no data about kidney function in the control group, the study conducted in one ethnic group.
How did they reach this conclusion?
long time follow up and the control group were potential donor according to their local guidelines and the large number of candidates as they have a huge living donation program in comparison to other European countries.
Please summarise this article in your own words
This study tries to assess the long term risks for kidney donors related to donation.
Number of such similar studies have been done but the controls were from general population and hence results seem to be confounding.
but in the present study controls were individuals who would have been eligible for kidney donation. similarly, in terms of cases marginal donors were excluded from the study.
Cases and controls were matched for age, gender, smoking, systolic BP, diastolic BP, BMI.
Past studies had produced skewed results favouring donor cases due to coexisting medical condition among controls which were from general population and otherwise ineligible for donation.
Many studies including general population as controls have observed that there was increased BP, albuminuria, and reduced renal function but medical fraternity has not considered loss of renal function after donation as long term risk factor for cardiovascular disease and /or mortality.
Though the present still also ahs limitatons but still it has raised ethical and medical issues regarding live kidney donation.
geographical locality difference between donors and controls, lack of data on renal function of controls, differences in follow up time between cases and controls were some of the main limiting factors.
But still, as per the current opinion, the present study doesnt advocate changing the concept of living donation and should be promoted if donors are willing for the same after accepting the long term consequences.
This is long prospective cohort designed to assess long term risks of kidney donation, it demonstrated a significant increase in ESRD, cardiovascular, and all-cause mortality during long-term follow-up after living kidney donation compared with a selected population of non-donors who would have met the criteria for donation. Although Previous studies have suggested that living kidney donors maintain long-term renal function and experience no increase in cardiovascular or all-cause mortality. However, most analyses have included control groups less healthy than the living donor population and have had relatively short follow-up periods.
A group of 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years.
There were 224 deaths among 1901 kidney donors from the initial inclusion group, 68 (30.4%) of which were due to cardiovascular disease. There were 2425 deaths among the 32,621 controls, 688 (28.4%) of which were due to cardiovascular disease. No donors died during or immediately after the surgical procedure. The survival curves were significantly different
(P<0.001).
A total of nine donors (0.47%) developed ESRD. All were family members. Median time from donation was 18.7 (10.3–24.3) years. mainly caused by immunological diseases In the control group, 22 individuals developed ESRD. The crude incidence of ESRD in donors was 302 per
million person-years. The overall incidence rate for development of ESRD in Norway is about 100 per million per person-year. After multiple imputation of missing values, the estimated HR for ESRD in kidney donors was 11.38 (4.37–29.63, P<0.001)
For the overall cohort of donors and controls, the median follow-up time was approximately 6
years. When assessing the influence of BP, body mass index (BMI), and smoking, a smaller cohort was followed for a relatively short time (median 2.1 years). Donation was not
found to be associated with an increase in all-cause mortality. no increase in all-cause mortality during in the initial 5–10 years after donation, but thereafter the survival curves began to deviate.
limitations this study: single centre All controls lived within one county, and all Caucasian.
How did they reach this conclusion?
*control group potentially eligible kidney donors (matching the donor group) as the general population maybe at include participant with high risk from the start.
*large study includes considerable number of participant minimizing error and bias
*long follow up enable to detect much more risks
Living kidney transplantation is associated with improved patient and graft survival compared to deceased donors. Kidney donation causes reduced renal function and causes proteinuria and rise of blood pressure in general population. Outcome of follow up studies of living kidney donors depends upon selection of control groups. If control group selected from general population, effect of organ donation could have underestimated here.
Results
During 1963-2007, among 2269 cases of live kidney donation, 1901 donors were included. Median follow up time was 15.1 years. Mean e GFR at donation was 104.7 ml/min/1.73m2.Controls were included from Health Study of Nord Trondelag population study. 32,621 persons were included as a control group. A total of 9 donors developed ESRD. Minimum time from donation was 18.7 years. Mostly due to immunological diseases.In the control groups 22 individuals develop ESRD in control groups.In this study, donors had a increased risk for developing ESRD compared with selected controls. This may be linked to genetic factors.
Limitations of this study is all controls live in one country whereas kidney donors were from all over Norway.
Potential donors should be informed of increased risk both in short term and long term.
Living donor transplantation is associated with better graft and patient outcome compared to deceased donor transplant.
Living donors undergo major surgery with risk of perioperative mortality in 0.03% of donors with higher risk for renal impairment, increased proteinuria and HTN more than that occurring with normal ageing resulting in increased risk of cardiovascular and all-cause mortality.
Available follow up studies included living kidney donors but the controls were from general population without exclusion of those with medical conditions and are ineligible for kidney donation making the controls less healthy than living donors, this selection bias leads to underestimation of the negative impact of donation
Also, these studies were of short term follow up and the effect of donation may need long term follow up to be detected.
This study aimed to compare all-cause mortality, risk for ESRD and cardiovascular risk in kidney donors and controls who were fit for kidney donation but didn’t donate.
It included 1901 donors followed up for 15.1 years and 32,621 controls who were eligible for kidney donation, followed up for 24.9 years
It showed that the risk for ESRD, cardiovascular disease and all-cause mortality is significantly higher in kidney donors when compared to nondonors fit for donation.
Most other studies included general population including those with cardiovascular disease, DM, HTN, CKD or malignancy while living donors are carefully selected making the results in favor of donor cohorts.
Applying donor health criteria to unselected population will result in a group with lower mortality rate and will be more relevant to be compared with living donors.
It was noticed that all-cause mortality increased after 10 years of donation.
Kidney donors are at high risk for elevated BP, albuminuria and renal impairment which are risk for cardiovascular and all-cause mortality.
It showed that donors have an increased risk for developing ESRD compared with selected donors.
Most of donors who need renal replacement therapy had primary renal disease which is uncommon in control group, this may be due to genetic factors as most of donors were relative to patients with ESKD and were at increased risk for renal disease not because of nephrectomy.
Limitations:
Controls were from one country but donors were from different countries, no data about renal function in the control group, longer follow up time in controls may increase detection of ESRD cases and results were difficult to extrapolate to unrelated donors and non-Caucasians
Strength:
long follow up time, complete follow up of all donors and controls with certified cause of death, data about cardiovascular risk factors (BMI, smoking and BP) were available for most patients.
The study showed that kidney donors have a potential increase long-term risks for kidney failure and mortality.
Potential donors should be informed about increased risks (although small but are present) associated with donation in short term and long term.
II. Long-term risks for kidney donors
This is one of the key articles that changed our understanding of the risk of donation.
1. Please summarise this article in your own words
Introduction:
Living donor kidney transplantation is the preferred treatment for end-stage renal disease (ESRD) because it is associated with improved graft and patient survival compared with transplantation from a deceased donor. Organ donation is unique in that the donor is subjected to surgery without having direct benefit from it. So careful evaluation of the potential donor to reduce this risk to the minimum is essential.
Although rare, perioperative mortality does occur during organ retrieval from living donors and have been estimated to occur in 0.2% of liver donors and 0.03% of kidney donors. It is possible, however, that living donors may be at increased risk.
Kidney donation inevitably leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in blood pressure (BP) greater than that attributable to normal
aging. These factors are associated with an increased risk for cardiovascular and all-cause mortality in the general population.
The aim of the present study was to estimate long-term all-cause mortality, cardiovascular mortality, and risk for ESRD in kidney donors compared with a selected control. Controls were included from the Health Study of Nord- Tr_ndelag (HUNT) population study. They were selected in a way that they would have been accepted for donation.
Results and discussion:
The result showed that all-cause death was significantly increased by 30% for donors compared with controls. There was a significant corresponding increase in cardiovascular death by 40% while the risk of ESRD was greatly and significantly increased to 11.38 (4.37–29.6). The overall incidence of ESRD among donors was 302 cases per million compared to 100 per million in the country.
Assessing competing risks for the outcomes of cardiovascular death and ESRD did not change our findings. Neither did repeating analyses after excluding donors with eGFR <80 ml/min per 1.73m.
Limitations of the study:
Donor were from one country.
Data about kidney function was not available.
Almost all the donor and control were Caucasians.
2. How did they reach this conclusion?
To reach this conclusion they selected the control group carefully and followed them for long time. Only subjects with BP <140/ 90mmHg and BMI <30 kg/m2 were included. Furthermore, only
those who rated their own health as ‘good’ or ‘excellent’ were selected. Individuals with diabetes, cardiovascular disease, or using BP-lowering medication were excluded.