Notes on the risks and benefits of kidney donation

By Derek Shiller @ 2021-11-26T15:02 (+39)

*edit: formatting changes for accessibility and added summary

Summary: The possible risks of kidney donation to the donor seem somewhat greater and the benefits to the recipient somewhat lesser than is generally conveyed in donation literature.

I considered donating a kidney two years ago. I went through the workup to get approval while simultaneously reading about it. Covid hit, and I put off a decision. I had some significant concerns which have prevented me from returning to the idea with enthusiasm. Since this is a decision others here have considered, I thought I'd share my takeaways here.

Donating a kidney is not a particularly effective compared with the other great opportunities available these days. Still, there may be good reasons to do it. It is helpful in a straightforward way; it isn't filtered through the administration of a charity or dependent on the speculative efficacy of an intervention. It is an option available to those who don't have good ways to use their time for other ends. It may serve as a lifelong reminder of one's commitment, perhaps solidifying one's identity as an altruist in a way that protects against value drift. Further, it is a signal of altruistic sincerity that most people will acknowledge. If you're into cause areas perceived as weird, like insect suffering or AI, making a transparently altruistic sacrifice might lead people to take your more eclectic interests more seriously.

These other considerations aside, the effectiveness of kidney donation turns on the value it provides the recipient and the cost to yourself. As far as I can tell (and I am no expert on these issues), the cost to yourself is not perfectly understood. The value to the recipient seems to be significant but not overwhelming in comparison to the risks. I suspect my comments come across as negative about donation. I think it is a net positive thing to do, but the risks and benefits should be acknowledged. Once I looked into it myself I felt misled by a lot of the pro-donation marketing.

Risks

• Losing a kidney reduces kidney function (Ibrahim et al. 2016). Your remaining kidney can react by becoming more effective in a process called 'hyperfiltration'. There was some worry early on that long-term hyperfiltration might be bad for your kidney. Experiments with rats suggest that if your kidney function gets too low, hyperfiltration may wear them out (Shimamura and Morrison 1975). It seems like this is not a major risk with humans who donate one kidney; the vast majority of donors do not experience the downward spiral of kidney function sometimes observed in rats. Still, donation does reduce your kidney function and kidney function also naturally diminishes over time (Denic et al. 2017). Even without donation, many people in their 70s, 80s, or 90s have rather poor kidney function. It seems to me that the greatest risks from donation come from a modest drop in kidney function that exacerbates the natural loss accompanying aging. The effects of such a modest reduction would be very difficult to detect with available datasets.

• There have been a number of studies on the effects of donation: some over the short term and a few over the long term. All of these studies have limitations that prevent them from uncovering small risks. Most of the longest studies (e.g. Williams, Oler, and Jorkasky 1986; Narkun-Burgess et al. 1993; Kasiske et al. 1995; Ramcharan and Matas 2002) were performed on very small samples of donors whose post-donation health was compared to the general population. These studies showed that donors are not significantly less healthy than the general population in the long term. However, none of these studies included people who donated in their 20s or 30s and lived to their 90s. (Nephrectomies have been performed since the 1860s but there were very few of them until donations started in earnest in the 1960s and 70s. Even then, most early patients were not followed for long after donation.)

  More recent studies (e.g. Mjøen et al. 2011; Garg et al. 2012; Muzaale et al. 2014; Mjøen et al. 2014) have attempted to match donors with equally healthy populations. Since donors are screened for various health factors and may be healthier than the average person, the fact that they remain as healthy as the average person may reflect a post-donation decline.

  Unfortunately, it is difficult to match donors with equally healthy controls. Studies that try to perform such matches use fairly blunt qualities, such as age, smoking status, and blood pressure. There are likely to be lots of more subtle biasing factors that need to be included for accurate results. Donors are distinctively altruistic. They may have better family relationships or more friends. This may affect their life expectancy. Until recently, most donations came from family members, who might share genetic predispositions or lifestyles with their recipients. Furthermore, we don't have good data going back very long, so these studies only bear on the effects of kidney donation over a few decades. If you're planning on living five or six decades after your donation, the lack of very long term studies may be worrisome.

• Studies on the effects of donation often look for kidney failure. A huge rise in the rate of kidney failure after donation would clearly be very worrying. But it is possible that donation is risky even if it doesn't lead to outright failure. Reduced kidney function correlates with a host of other issues. Donation raises blood pressure (Boudville et al. 2006), and increased blood pressure is associated with all-cause mortality. Reduced kidney function is also associated with all-cause mortality (Go et al. 2004). It may be that these associations are not indicative of negative effects of kidney donation. It may be that the kind of functional reduction associated with donation is less problematic, or that reduced kidney function is a symptom, rather than a cause, of other problems. Or perhaps people who have poor kidney function lead lifestyles that harm their health in other ways. Still, as far as I can tell, we don't yet know. Given the extent of known functional loss, the available evidence is consistent with the possibility that donation will take a year off the life of a 20 or 30-something in expectation, assuming medical treatment doesn't improve.

• The standards used to screen donors seem relaxed to me. In order to be eligible to donate, you need to have a normal GFR (a measure of kidney function), i.e. above 90. This ensures that you're not on the verge of kidney failure, but it doesn't say much about the long-term health of your kidneys. GFR naturally decreases over time, and so a GFR of 90 when you're 70 is great, but may be concerning when you're 20.

  Furthermore, it seems impossible at the present to accurately measure your potential kidney function. Tests of GFR vary from day to day. They only test what your kidney is doing, not what work it could be doing. Since kidneys can compensate for reduced capacity, their potential is hard to assess without directly inspecting them (Merzkani et al. 2021). This isn't feasible to do to screen donors, so hospitals use imperfect tests to evaluate GFR. Furthermore, common tests for GFR using serum creatinine may be affected by external factors like a vegetarian diet (Delanghe et al. 1989; Bosch et al. 1983) in ways that are not totally clear to me and don't seem to be taken into consideration in the process.

Benefits

• The alternative for a patient to receiving a donor kidney is perpetual dialysis. There are a few ways to do dialysis, but each is uncomfortable and disruptive. Nevertheless, despite the significant inconvenience, patients on dialysis can continue to lead a reasonably normal life (Gorodetskaya et al. 2005).

  Many people who start dialysis die relatively soon after, but going on dialysis is not itself a death sentence. Many people go on dialysis at an advanced age. Many are not suitable candidates for a transplant. The life expectancy for those on the transplant list is comparatively high (Rana A, 2018), suggesting that people on the list are not likely to die immediately without a donor kidney. The difference between life expectancy with and without a donor kidney is not as high as I originally thought.

• A donor kidney won't last forever in the recipient's body. Recipients' immune systems fight the new organs, and will eventually shut them down. While this may happen very quickly, the average kidney lasts a fair while. After a decade or two, the recipient is likely to need another kidney or to resume dialysis. It is possible that in a few decades artificial kidneys will be available. So a donation now might be a bridge to a permanent solution. There has been hype about artificial kidneys being around the corner for a while, and it has not yet materialized, so we should probably not be too confident about this.

• Recipients of donor kidneys must remain on immunosuppressants. Transplantation doesn't fully resolve all of the issues faced by those with kidney failure, and while it improves quality of life, it doesn't restore it to normal (Von der Lippe et al. 2014).

• Non-directed donations can be used to start a chain of donations. In the current system, most people who are waiting to be part of a chain won't too wait long (Paired Exchange Results Quarterly Report 2018). Given the current needs (at least as of the last few years), starting a chain doesn't seem to me to be a major reason in favor of donating. Still, your donation will probably mean that a number of people get a kidney somewhat sooner.

• If you're giving in a chain, the most significant beneficiary of your non-directed donation isn't likely to be the person who receives your kidney. That person is likely to be able to get another in a few months. Getting your kidney will save them some time on dialysis or waiting for a new kidney, and may slightly improve their ability to accept the new kidney, but it doesn't seem to me to be too significant.

  Nor is the most significant beneficiary the person at the end of the chain. There is a waitlist for organs and one way to end a chain is to dip into that waitlist. (Everyone else in the chain gets there because they have someone willing to give up an organ for them, even if they can't give it to them). The person at the top of the waitlist may be fairly likely (though I haven't seen data on this) to get a kidney eventually anyway.

  Instead, I think the most significant beneficiary is whoever is on the waitlist who would have fallen off the waitlist due to ill-health or giving up but for your donation advancing them a position in the waitlist by satisfying the needs of the person at the front. If this person is a more marginal candidate for donation, then it may mean that they benefit more or less from receiving a kidney. It may mean that they would do less well on dialysis. It may also mean that they live for less time with the donated kidney. This seems a potentially significant consideration, but I have no idea how to evaluate this, or which way it bears on the decision.

• Dialysis is expensive. By donating, you save an insurance provider a lot of money. Possibly in the hundreds of thousands of dollars. The U.S. government pays a lot for dialysis and it may affect their ability to support other medical treatments. On the other hand, a person who lives longer may have a greater need for medical treatment later in life, so saving money on dialysis needn't transfer to saving money overall. Furthermore, it is unlikely that your donation will change anything about how much people are taxed or which medical treatments are covered.

References

Bosch, Juan P, Anna Saccaggi, Allan Lauer, Claudio Ronco, Mario Belledonne, and Sheldon Glabman. 1983. “Renal Functional Reserve in Humans: Effect of Protein Intake on Glomerular Filtration Rate.” The American Journal of Medicine 75 (6). Elsevier: 943–50.

Boudville, Neil, GV Ramesh Prasad, Greg Knoll, Norman Muirhead, Heather Thiessen-Philbrook, Robert C Yang, M Patricia Rosas-Arellano, Abdulrahman Housawi, and Amit X Garg. 2006. “Meta-Analysis: Risk for Hypertension in Living Kidney Donors.” Annals of Internal Medicine 145 (3). American College of Physicians: 185–96.

Delanghe, J, JP De Slypere, M De Buyzere, J Robbrecht, R Wieme, and A Vermeulen. 1989. “Normal Reference Values for Creatine, Creatinine, and Carnitine Are Lower in Vegetarians.” Clinical Chemistry 35 (8). Oxford University Press: 1802–3.

Denic, Aleksandar, John C Lieske, Harini A Chakkera, Emilio D Poggio, Mariam P Alexander, Prince Singh, Walter K Kremers, Lilach O Lerman, and Andrew D Rule. 2017. “The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging.” Journal of the American Society of Nephrology 28 (1). Am Soc Nephrol: 313–20.

Garg, Amit X, Aizhan Meirambayeva, Anjie Huang, Joseph Kim, GV Ramesh Prasad, Greg Knoll, Neil Boudville, et al. 2012. “Cardiovascular Disease in Kidney Donors: Matched Cohort Study.” Bmj 344. British Medical Journal Publishing Group: e1203.

Go, Alan S, Glenn M Chertow, Dongjie Fan, Charles E McCulloch, and Chi-yuan Hsu. 2004. “Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization.” New England Journal of Medicine 351 (13). Mass Medical Soc: 1296–1305.

Gorodetskaya, Irina, Stefanos Zenios, Charles E Mcculloch, Alan Bostrom, Chi-Yuan Hsu, Andrew B Bindman, Alan S Go, and Glenn M Chertow. 2005. “Health-Related Quality of Life and Estimates of Utility in Chronic Kidney Disease.” Kidney International 68 (6). Elsevier: 2801–8.

Ibrahim, Hassan N, Robert N Foley, Scott A Reule, Richard Spong, Aleksandra Kukla, Naim Issa, Danielle M Berglund, Gretchen K Sieger, and Arthur J Matas. 2016. “Renal Function Profile in White Kidney Donors: The First 4 Decades.” Journal of the American Society of Nephrology 27 (9). Am Soc Nephrol: 2885–93.

Kasiske, Bertram L, Jennie Z Ma, Thomas A Louis, and Suzanne K Swan. 1995. “Long-Term Effects of Reduced Renal Mass in Humans.” Kidney International 48 (3). Elsevier: 814–19.

Merzkani, Massini A., Aleksandar Denic, Ramya Narasimhan, Camden L. Lopez, Joseph J. Larson, Walter K. Kremers, Harini A. Chakkera, et al. 2021. “Kidney Microstructural Features at the Time of Donation Predict Long-Term Risk of Chronic Kidney Disease in Living Kidney Donors.” Mayo Clinic Proceedings 96 (1): 40–51.

Mjøen, Geir, Stein Hallan, Anders Hartmann, Aksel Foss, Karsten Midtvedt, Ole Øyen, Anna Reisæter, et al. 2014. “Long-Term Risks for Kidney Donors.” Kidney International 86 (1). Elsevier: 162–67.

Mjøen, Geir, Anna Reisaeter, Stein Hallan, Pål-Dag Line, Anders Hartmann, Karsten Midtvedt, Aksel Foss, Dag Olav Dahle, and Hallvard Holdaas. 2011. “Overall and Cardiovascular Mortality in Norwegian Kidney Donors Compared to the Background Population.” Nephrology Dialysis Transplantation 27 (1). Oxford University Press: 443–47.

Muzaale, Abimereki D, Allan B Massie, Mei-Cheng Wang, Robert A Montgomery, Maureen A McBride, Jennifer L Wainright, and Dorry L Segev. 2014. “Risk of End-Stage Renal Disease Following Live Kidney Donation.” Jama 311 (6). American Medical Association: 579–86.

Narkun-Burgess, Deborah M, Charles R Nolan, James E Norman, William F Page, Peter L Miller, and Timothy W Meyer. 1993. “Forty-Five Year Follow-up After Uninephrectomy.” Kidney International 43 (5). Elsevier: 1110–5.

2018. “Paired Exchange Results Quarterly Report.” https://www.kidneyregistry.org/pages/p508/NKR_Qtrly_RPt_Q4_2018.php.

Ramcharan, Thiagarajan, and Arthur J Matas. 2002. “Long-Term (20–37 Years) Follow-up of Living Kidney Donors.” American Journal of Transplantation 2 (10). Wiley Online Library: 959–64.

Rana A, O’Mahony C, Murthy B. 2018. “Waitlist Survival Is Approaching Survival After Kidney Transplantation.” https://atcmeetingabstracts.com/abstract/waitlist-survival-is-approaching-survival-after-kidney-transplantation/.

Shimamura, Tetsuo, and Ashton B Morrison. 1975. “A Progressive Glomerulosclerosis Occurring in Partial Five-Sixths Nephrectomized Rats.” The American Journal of Pathology 79 (1). American Society for Investigative Pathology: 95.

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