Potential Risks of Living Kidney Donation

Living kidney transplantation is an important therapeutic option for many patients with ESRD. Recent blogs have focused on incentives/removal of financial disincentives to living donation and best practices in living kidney donation. In this blog I have asked Peter Reese and John Gill to focus on the important topic of our evolving understanding of the potential risks of living kidney donation.

Potential Risks of Living Kidney Donation

John Gill, M.D., M.S., St. Paul's Hospital
Peter Reese, M.D., M.S.C.E., University of Pennsylvania

Recent studies from the U.S. and Norway confirmed that ESRD after living kidney donation is a rare event.^1,2 In the U.S. study, 99 ESRD events were identified in the cohort of over 96,000 donors during a median follow up of 7.5 years.¹ The estimated cumulative incidence of ESRD at 15 years was 30.8/10,000 donors. In Norway, 9 out of 1901 donors developed ESRD at a median of 18.7 years post donation, and ESRD events were primarily attributed to immunological reasons.² Of potential concern, both studies reported the ESRD risks to be higher than those in matched cohorts, but these comparisons had limitations,^3,4 and the authors did not conclude that the information warranted change in practice.

These studies provide the best information about ESRD risk after living donation and focus attention on the need for long-term outcomes. Because ESRD risk may depend on the number of years in a single-kidney state, young kidney donors (e.g., in their 20s) may have a greater risk of ESRD in their lifetime. Outcomes for donors with risk factors for kidney disease such as obesity or hypertension are insufficiently described in current studies and risks may be higher in such donors. African-American ethnicity is associated with an increased risk of ESRD, and African-American donors have a higher risk than white donors,⁵ raising questions about the best approach for evaluating and selecting African-American donors. Given the rarity of ESRD and the long time interval between donation and events, the best source of new information will likely not come from enhanced center follow-up practices, but instead from national healthcare databases that are able to identify meaningful health outcomes across large donor populations.⁶ Targeted studies in sub-groups where there is more uncertainty regarding risk are needed.

Most kidney donors are women and some are in their reproductive years. Because both kidney donation and pregnancy lead to hyperfiltration, there is a biological basis for concern that pregnancy might cause complications for a woman in a single-kidney state. A national study of Norwegian live donors^7,8 and a single center study from the University of Minnesota⁸ reported that prior live kidney donors do have an elevated rate of pre-eclampsia (5 – 6%) in post-donation pregnancies, after adjustment for pre-donation rates of pregnancy complications.

Lastly, a number of investigations have illuminated the financial consequences of kidney donation. These costs may be incurred in diverse ways including lost wages, transportation, or need for childcare. Recovery time may be particularly burdensome for donors whose job security would be jeopardized by a multi-week absence and/or a requirement for reduced physical activity at work. In Canada, the average costs to donors was estimated to be $3,500, and 15% experienced costs >$8,000.⁹ Recent work suggested these concerns may be amplified during periods of economic uncertainty and may have contributed to the decrease in live kidney donation in the US since 2004.¹⁰

The new information about the long-term risks of donation is both reassuring and unsettling - because our understanding remains incomplete. Until further studies are published, transplant professionals must often rely on clinical judgment in selecting donors. We need to ensure that potential donors understand that recent information shows that living donation poses a low risk of major complications such as ESRD, but that there are important limitations in our understanding of long-term outcomes. While we await further long-term data, new strategies to inform donor decision-making including the use of decision aids should be advanced.

1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586. doi: 510.1001/jama.2013.285141.
2. Mjoen G, Hallan S, Hartmann A, et al. Long-term risks for kidney donors. Kidney Int. 2014;86(1):162-167. doi: 110.1038/ki.2013.1460. Epub 2013 Nov 1027.
3. Kaplan B, Ilahe A. Quantifying risk of kidney donation: the truth is not out there (yet). Am J Transplant. 2014;14(8):1715-1716. doi: 1710.1111/ajt.12804. Epub 12014 May 12827.
4. Gill JS, Tonelli M. Understanding rare adverse outcomes following living kidney donation. JAMA. 2014;311(6):577-579. doi: 510.1001/jama.2013.285142.
5. Cherikh WS, Young CJ, Kramer BF, Taranto SE, Randall HB, Fan PY. Ethnic and gender related differences in the risk of end-stage renal disease after living kidney donation. Am J Transplant. 2011;11(8):1650-1655. doi: 1610.1111/j.1600-6143.2011.03609.x. Epub 02011 Jun 03614.
6. Leichtman A, Abecassis M, Barr M, et al. Living kidney donor follow-up: state-of-the-art and future directions, conference summary and recommendations. Am J Transplant. 2011;11(12):2561-2568. doi: 2510.1111/j.1600-6143.2011.03816.x. Epub 02011 Nov 03814.
7. Reisaeter AV, Roislien J, Henriksen T, Irgens LM, Hartmann A. Pregnancy and birth after kidney donation: the Norwegian experience. Am J Transplant. 2009;9(4):820-824. doi: 810.1111/j.1600-6143.2008.02427.x. Epub 02008 Oct 02426.
8. Ibrahim HN, Akkina SK, Leister E, et al. Pregnancy outcomes after kidney donation. Am J Transplant. 2009;9(4):825-834.
9. Klarenbach S, Gill JS, Knoll G, et al. Economic consequences incurred by living kidney donors: a Canadian multi-center prospective study. Am J Transplant. 2014;14(4):916-922. doi: 910.1111/ajt.12662. Epub 12014 Mar 12665.
10. Gill J, Dong J, Gill J. Population Income and Longitudinal Trends in Living Kidney Donation in the United States. J Am Soc Nephrol. 2014:2014010113.