NIHR DC Discover

NIHR Signal Living kidney donors have only a very small increased risk of kidney failure and pre-eclampsia

Published on 15 May 2018

doi: 10.3310/signal-00591

Healthy kidney donors, of both sexes, have no extra risk of death or other major chronic diseases amongst donors up to 15 years after donation, except for a small increase in risk of end-stage renal disease. One in 2,000 people per year will develop kidney failure following donation of a kidney compared to one in 10,000 among non-donors. Of donors who become pregnant, three extra in 100 women will have pre-eclampsia.

This part NIHR-funded systematic review and meta-analysis included 52 studies. It summarised evidence about the mid- and long-term health risks associated with living kidney donation in adults.

Kidney transplant from a living donor remains the best available treatment for end-stage renal disease. This information will help potential donors to understand their risks to health when weighed against the potential benefits to the planned transplant recipient.

Share your views on the research.

Why was this study needed?

Kidney donation from a living donor substantially improves the survival of people with kidney failure. In the UK, over 1,000 kidney transplants from living donors are performed every year. The chance of long-term success with the new kidney is better following living donation compared to kidneys from deceased donors.

Although living kidney donation can greatly benefit recipients, a potential donor, with their healthcare provider, must also consider the possible risk to their health. Full consideration of these risks is vital for supporting informed consent. However, there remains some uncertainty regarding the mid- and long-term risks associated with kidney donation. 

Previous reviews have reported only a limited range of health outcomes and did not include all available data. This is the first systematic review and meta-analysis to quantify the mid-term health risks of living kidney donation, compared to non-donors, for a broad range of health outcomes.

What did this study do?

This was a systematic review and meta-analysis of 52 observational studies comparing health outcomes for 118,426 kidney donors and 117,656 controls. Most studies were from the US, two from the UK, mainly using registers of kidney donors with matched non-donors from other sources.

The main analysis included 28 studies published since from 2,000. These were filtered for quality, though there were only a few studies for each outcome.

The matching of controls to donors regarding age, sex, smoking and pre-existing conditions varied across the studies. Donors may have also had an increased likelihood of disease diagnosis due to closer medical surveillance. This might have artificially inflated the rates.

What did it find?

  • Death from any cause was lower in the donor group, occurring in 1.7% of cases compared to 5% of the control group over an average of six to 15 years follow-up (adjusted risk ratio [aRR] 0.60, 95% confidence interval [CI] 0.31 to 1.10; four studies).
  • Across the higher quality studies included in the review, there was no evidence of increased risk of cancer, cardiovascular disease, type 2 diabetes, hypertension, gestational hypertension, low birth weight, or preterm birth in the donor group compared to the control group.
  • Donors had a higher overall risk of end-stage renal disease (ESRD) than controls. However, absolute risk was low, with one in 2,000 people per year developing ESRD in the donor group compared to one in 10,000 people per year in the control group (aRR 8.83, 95% CI 1.02 to 20.93; three studies).
  • Donors may have had a higher overall risk of pre-eclampsia than controls. Donors developed pre-eclampsia in almost six in 100 pregnancies compared to around three in 100 pregnancies in the control group (aRR 2.12, 95% CI 1.06 to 4.27; three studies). These studies were very heterogeneous.

What does current guidance say on this issue?

The British Transplant Society 2018 guideline, recommends that for a living donor to give valid consent for donation, they must be properly informed about the risks, relevant to all donors, and any specific individual risks.

The information should include an acknowledgement that the baseline risk of kidney failure is increased in kidney donors. Information should consider pre-existing factors that raise an individual’s risk including age, sex, race, BMI and family history of renal disease. Additionally, it is recommended women are informed of a greater risk of pregnancy-induced hypertension after kidney donation.

What are the implications?

This review supports current recommendations that informed consent should include discussions about all potential health risks, even when evidence is uncertain. The increased risk of pre-eclampsia should be included in future guidelines.

Given there are 5,000 people on the waiting list for a kidney, the finding that the risks to the donor are low is welcome. However, longer-term risk of chronic disease or death beyond the average five to 15 years of follow-up from these studies remains uncertain. This highlights the importance of accurate reporting to the Living Donor Registry in the UK so that longer-term outcomes can be captured.

Citation and Funding

O'Keeffe LM, Ramond A, Oliver-Williams C, et al. Mid-and long-term health risks in living kidney donors: a systematic review and meta-analysis. Ann Internal Med. 2018;168(4):276-84.

Bibliography

BTS. Guidelines for living donor kidney transplantation. Macclesfield: British Transplantation Society; 2018.  

Nemati E, Einollahi B, Pezeshki ML, et al. Does kidney transplantation with deceased or living donor affect graft survival? Nephrourol Mon. 2014;6(4):e12182.

NHS Blood and Transplant. Organ donation and Transplantation Activity Data: United Kingdom. London: NHS Blood and Transplant; 2018.

Koo DD, Welsh KI, Mclaren AJ, et al. Cadaver versus living donor kidneys: impact of donor factors on antigen induction before transplantation. Kidney Int. 1999;56(4):1551-9.

Reese PP, Boudville N, Garg AX. Living kidney donation: outcomes, ethics, and uncertainty. Lancet. 2015;385(9981):2003-13.

Why was this study needed?

Kidney donation from a living donor substantially improves the survival of people with kidney failure. In the UK, over 1,000 kidney transplants from living donors are performed every year. The chance of long-term success with the new kidney is better following living donation compared to kidneys from deceased donors.

Although living kidney donation can greatly benefit recipients, a potential donor, with their healthcare provider, must also consider the possible risk to their health. Full consideration of these risks is vital for supporting informed consent. However, there remains some uncertainty regarding the mid- and long-term risks associated with kidney donation. 

Previous reviews have reported only a limited range of health outcomes and did not include all available data. This is the first systematic review and meta-analysis to quantify the mid-term health risks of living kidney donation, compared to non-donors, for a broad range of health outcomes.

What did this study do?

This was a systematic review and meta-analysis of 52 observational studies comparing health outcomes for 118,426 kidney donors and 117,656 controls. Most studies were from the US, two from the UK, mainly using registers of kidney donors with matched non-donors from other sources.

The main analysis included 28 studies published since from 2,000. These were filtered for quality, though there were only a few studies for each outcome.

The matching of controls to donors regarding age, sex, smoking and pre-existing conditions varied across the studies. Donors may have also had an increased likelihood of disease diagnosis due to closer medical surveillance. This might have artificially inflated the rates.

What did it find?

  • Death from any cause was lower in the donor group, occurring in 1.7% of cases compared to 5% of the control group over an average of six to 15 years follow-up (adjusted risk ratio [aRR] 0.60, 95% confidence interval [CI] 0.31 to 1.10; four studies).
  • Across the higher quality studies included in the review, there was no evidence of increased risk of cancer, cardiovascular disease, type 2 diabetes, hypertension, gestational hypertension, low birth weight, or preterm birth in the donor group compared to the control group.
  • Donors had a higher overall risk of end-stage renal disease (ESRD) than controls. However, absolute risk was low, with one in 2,000 people per year developing ESRD in the donor group compared to one in 10,000 people per year in the control group (aRR 8.83, 95% CI 1.02 to 20.93; three studies).
  • Donors may have had a higher overall risk of pre-eclampsia than controls. Donors developed pre-eclampsia in almost six in 100 pregnancies compared to around three in 100 pregnancies in the control group (aRR 2.12, 95% CI 1.06 to 4.27; three studies). These studies were very heterogeneous.

What does current guidance say on this issue?

The British Transplant Society 2018 guideline, recommends that for a living donor to give valid consent for donation, they must be properly informed about the risks, relevant to all donors, and any specific individual risks.

The information should include an acknowledgement that the baseline risk of kidney failure is increased in kidney donors. Information should consider pre-existing factors that raise an individual’s risk including age, sex, race, BMI and family history of renal disease. Additionally, it is recommended women are informed of a greater risk of pregnancy-induced hypertension after kidney donation.

What are the implications?

This review supports current recommendations that informed consent should include discussions about all potential health risks, even when evidence is uncertain. The increased risk of pre-eclampsia should be included in future guidelines.

Given there are 5,000 people on the waiting list for a kidney, the finding that the risks to the donor are low is welcome. However, longer-term risk of chronic disease or death beyond the average five to 15 years of follow-up from these studies remains uncertain. This highlights the importance of accurate reporting to the Living Donor Registry in the UK so that longer-term outcomes can be captured.

Citation and Funding

O'Keeffe LM, Ramond A, Oliver-Williams C, et al. Mid-and long-term health risks in living kidney donors: a systematic review and meta-analysis. Ann Internal Med. 2018;168(4):276-84.

Bibliography

BTS. Guidelines for living donor kidney transplantation. Macclesfield: British Transplantation Society; 2018.  

Nemati E, Einollahi B, Pezeshki ML, et al. Does kidney transplantation with deceased or living donor affect graft survival? Nephrourol Mon. 2014;6(4):e12182.

NHS Blood and Transplant. Organ donation and Transplantation Activity Data: United Kingdom. London: NHS Blood and Transplant; 2018.

Koo DD, Welsh KI, Mclaren AJ, et al. Cadaver versus living donor kidneys: impact of donor factors on antigen induction before transplantation. Kidney Int. 1999;56(4):1551-9.

Reese PP, Boudville N, Garg AX. Living kidney donation: outcomes, ethics, and uncertainty. Lancet. 2015;385(9981):2003-13.

Mid- and Long-Term Health Risks in Living Kidney Donors: A Systematic Review and Meta-analysis

Published on 31 January 2018

O'Keeffe, L. M.,Ramond, A.,Oliver-Williams, C.,Willeit, P.,Paige, E.,Trotter, P.,Evans, J.,Wadstrom, J.,Nicholson, M.,Collett, D.,Di Angelantonio, E.

Ann Intern Med , 2018

Background: Long-term health risks for adults who donate kidneys are unclear. Purpose: To summarize evidence about mid- and long-term health risks associated with living kidney donation in adults. Data Sources: PubMed, Embase, Scopus, and PsycINFO without language restriction from April 1964 to July 2017. Study Selection: Observational studies with at least 1 year of follow-up that compared health outcomes in adult living kidney donors versus nondonor populations. Data Extraction: Two investigators independently extracted study data and assessed study quality. Data Synthesis: 52 studies, comprising 118 426 living kidney donors and 117 656 nondonors, were included. Average follow-up was 1 to 24 years. No evidence suggested higher risk for all-cause mortality, cardiovascular disease, hypertension, type 2 diabetes, or adverse psychosocial health outcomes in living kidney donors than in nondonor populations. Donors had higher diastolic blood pressure, lower estimated glomerular filtration rates, and higher risk for end-stage renal disease (ESRD) (relative risk [RR], 8.83 [95% CI, 1.02 to 20.93]) and preeclampsia in female donors (RR, 2.12 [CI, 1.06 to 4.27]). Despite the increased RR, donors had low absolute risk for ESRD (incidence rate, 0.5 event [CI, 0.1 to 4.9 events] per 1000 person-years) and preeclampsia (incidence rate, 5.9 events [CI, 2.9 to 8.9 events] per 100 pregnancies). Limitation: Generalizability was limited by selected control populations, few studies reported pregnancy-related outcomes, and few studies were from low- and middle-income countries. Conclusion: Although living kidney donation is associated with higher RRs for ESRD and preeclampsia, the absolute risk for these outcomes remains low. Compared with nondonor populations, living kidney donors have no increased risk for other major chronic diseases, such as type 2 diabetes, or for adverse psychosocial outcomes. Primary Funding Source: National Health Service Blood and Transplant and National Institute for Health Research. (PROSPERO: CRD42017072284).

Expert commentary

Donating a kidney to a relative or friend (or altruistically to anyone) completely transforms the recipient’s life and that of their family.

This excellent research will ensure that donors can be reassured even more strongly about the minimal long-term risks for them as a kidney donor. It does also, however, show the importance of life-long follow-up for the rare possibility of future problems to their health.

Health services should ensure this can happen easily, for example with an annual check of blood pressure or kidney blood test for the donor.

Jeremy Levy, Professor of Practice (Medicine), Director of Clinical Academic Training, Imperial College London; Consultant Nephrologist, Imperial College Healthcare NHS Trust

Expert commentary

World-wide living donor transplantation transforms the lives of more than 27,000 people with kidney failure each year. The risk to their donors must be articulated as clearly as possible.

This review increases the certainty with which we can reassure them that they are not at risk of reduced life expectancy or of developing cardiovascular or diabetic comorbidity.

Donation reduces kidney function, and the risk of getting kidney failure is real, but very uncommon, happening to one of 2,000 donors each year. The risks to future pregnancy are less clear, and this should be highlighted to women contemplating donation.

Simon Davies, Professor of Nephrology & Dialysis Medicine, Keele University; Consultant Nephrologist, University Hospital of North Midlands