Pediatr Transplantation 2014: 18: 319–320
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12251
Editorial
Teen donors, adult problems? Evaluating the long-term risks of living kidney donation from adolescents Kidney transplantation from a living donor has been shown to be the preferred treatment for end-stage kidney disease (ESKD). The resulting increase in living donor transplantation has been paralleled by a growing interest in living donor safety and long-term outcomes. Although the short-term risks surrounding donation are well described and numerous studies have shown favorable long-term outcomes among living kidney donors, questions still do exist, especially for higher risk donor groups such as those with hypertension, obesity, reduced renal function, nephrolithiasis, etc. The study by MacDonald and colleagues in this issue of Pediatric Transplantation describes the long-term outcomes of one group which has been considered high-risk: adolescent living kidney donors (1). The authors report important outcomes including vital status, eGFR, hypertension, diabetes, and proteinuria among adolescent living kidney donors (those aged less than 18 at time of donation) and compare them to matched young adult living kidney donors (those aged 18– 30 yr at time of donation). Both donors and controls have very long-term follow-up (30 yr). The authors conclude that adolescent donors do not appear to be at higher risk of long-term complications than their young adult donor controls. Living donation from adolescent donors is rare, and their outcomes have never been reported in a systematic way, making this paper a unique and important contribution. Adolescent living donation has also become less common over the past few decades, so this paper likely provides the best long-term data available for this group. One significant challenge in studying long-term donor outcomes is selecting the appropriate control group. Many studies have compared outcomes among healthy, screened donors to the general population and showed that they fare as
well, or in fact better, than the general population – the latter phenomenon no doubt due to selection bias. A more recent study of donors and carefully matched controls demonstrated an increase in end-stage kidney disease, cardiovascular disease, and all-cause mortality, differences only observed after more than 10 yr post-donation (2). Another recent study found a small absolute lifetime risk of ESKD for living kidney donors (90 per 10 000), but a large relative risk when compared to healthy individuals who underwent similar screening and would likely have qualified to donate (who had an ESKD risk of 14 per 10 000) (3). The use of an older control group faces the problem of lead time bias. Adolescent donors may be at higher risk precisely because they have a longer residual life expectancy than older donors, and therefore longer “follow-up period” in which to develop health problems. The authors minimized this effect by choosing younger adult donors (18–30 yr old), but not entirely. Donors were younger than controls and had equal lengths of follow-up, thus were still younger at last follow-up (50 vs. 56 yr old). The mean time to the development of hypertension postdonation was similar in donors and controls (25.6 vs. 24.9 yr), but because of the initial age difference, adolescent donors would have developed hypertension at 42.7 yr of age vs. 49.1 yr in controls. Similarly, while hypertension developed in 35.9% of donors at age 50 vs. 39.4% of controls at age 56, it is probable that a significant number of adolescent donors would develop hypertension between the ages of 50 and 56 (4). Following both groups until the same age, not the same time post-donation, would provide a more meaningful comparison. The ideal control group to study the impact of donation on the health of adolescents would be a cohort of matched adolescent non-donors who 319
Editorial
were healthy enough to donate; this would require a prospective study, or careful retrospective matching (2, 3). A control group of adult donors can only be used to determine whether adolescent donors are at higher risk than adult donors, a group that themselves may be at higher risk. This article is significant because it is unlikely that a larger cohort of adolescent donors will be described, nor one that has been followed for so long and so comprehensively. We are less confident than the authors, however, in concluding that adolescent donors are not at higher medical risk due to the small sample size and the nature of the control group. We agree with the authors that this paper should not be seen as endorsing the routine use of adolescent living donors, as the major concern with using donors in this age group has always been their ability to provide adequate informed consent to donate. If it could be definitively shown that an adolescent donor has the same long-term risks as an adult donor, this would add to the information available for pretransplant counseling, but concerns with limited capacity to interpret and act on that information would remain. There is a chance that this information may actually add to coercion of adolescent donors, as donation that is seen as “safe” may rob reluctant teens of a chance to “back out” gracefully. While concerns with coercion are not limited to the adolescent donor, they may be magnified in this situation, because adolescent donors are likely members of the potential recipient’s family and are more likely to be emotionally and financially dependent on those urging
320
them to donate. While this paper may add to the prognostic information that the living donor assessment team is able to provide to an adolescent, it cannot solve the consent and coercion issues that can arise. When an adolescent presents as a potential living donor, teams should continue to apply the criteria of the US Live Organ Donor Consensus group and the American Academy of Pediatrics Committee on Bioethics (as outlined in the MacDonald paper). Only if those criteria are met, should the transplant evaluation proceed, and it is then that this paper can help teams in counseling the potential adolescent donor and his or her family about the long-term risks of donating. A. Goldberg1 and L. Storsley2 1 Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada 2 Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada E-mail: [email protected]
References 1. MACDONALD D, KUKLA A, JACKSON S, et al. Medical outcomes of adolescent live kidney donors. Pediatric Transplantation 2014: 18: 336–341. 2. MJØEN G, HALLAN S, HARTMANN A, et al. Long-term risks for kidney donors. Kidney Int 2013: doi: 10.1038/ki.2013.460. 3. MUZAALE AD, MASSIE AB, WANG MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA 2014: 311: 579–586. 4. DANNENBERG AL, GARRISON RJ, KANNEL WB. Incidence of hypertension in the Framingham Study. Am J Pub Health 1988: 78: 676–679.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12251
Editorial
Teen donors, adult problems? Evaluating the long-term risks of living kidney donation from adolescents Kidney transplantation from a living donor has been shown to be the preferred treatment for end-stage kidney disease (ESKD). The resulting increase in living donor transplantation has been paralleled by a growing interest in living donor safety and long-term outcomes. Although the short-term risks surrounding donation are well described and numerous studies have shown favorable long-term outcomes among living kidney donors, questions still do exist, especially for higher risk donor groups such as those with hypertension, obesity, reduced renal function, nephrolithiasis, etc. The study by MacDonald and colleagues in this issue of Pediatric Transplantation describes the long-term outcomes of one group which has been considered high-risk: adolescent living kidney donors (1). The authors report important outcomes including vital status, eGFR, hypertension, diabetes, and proteinuria among adolescent living kidney donors (those aged less than 18 at time of donation) and compare them to matched young adult living kidney donors (those aged 18– 30 yr at time of donation). Both donors and controls have very long-term follow-up (30 yr). The authors conclude that adolescent donors do not appear to be at higher risk of long-term complications than their young adult donor controls. Living donation from adolescent donors is rare, and their outcomes have never been reported in a systematic way, making this paper a unique and important contribution. Adolescent living donation has also become less common over the past few decades, so this paper likely provides the best long-term data available for this group. One significant challenge in studying long-term donor outcomes is selecting the appropriate control group. Many studies have compared outcomes among healthy, screened donors to the general population and showed that they fare as
well, or in fact better, than the general population – the latter phenomenon no doubt due to selection bias. A more recent study of donors and carefully matched controls demonstrated an increase in end-stage kidney disease, cardiovascular disease, and all-cause mortality, differences only observed after more than 10 yr post-donation (2). Another recent study found a small absolute lifetime risk of ESKD for living kidney donors (90 per 10 000), but a large relative risk when compared to healthy individuals who underwent similar screening and would likely have qualified to donate (who had an ESKD risk of 14 per 10 000) (3). The use of an older control group faces the problem of lead time bias. Adolescent donors may be at higher risk precisely because they have a longer residual life expectancy than older donors, and therefore longer “follow-up period” in which to develop health problems. The authors minimized this effect by choosing younger adult donors (18–30 yr old), but not entirely. Donors were younger than controls and had equal lengths of follow-up, thus were still younger at last follow-up (50 vs. 56 yr old). The mean time to the development of hypertension postdonation was similar in donors and controls (25.6 vs. 24.9 yr), but because of the initial age difference, adolescent donors would have developed hypertension at 42.7 yr of age vs. 49.1 yr in controls. Similarly, while hypertension developed in 35.9% of donors at age 50 vs. 39.4% of controls at age 56, it is probable that a significant number of adolescent donors would develop hypertension between the ages of 50 and 56 (4). Following both groups until the same age, not the same time post-donation, would provide a more meaningful comparison. The ideal control group to study the impact of donation on the health of adolescents would be a cohort of matched adolescent non-donors who 319
Editorial
were healthy enough to donate; this would require a prospective study, or careful retrospective matching (2, 3). A control group of adult donors can only be used to determine whether adolescent donors are at higher risk than adult donors, a group that themselves may be at higher risk. This article is significant because it is unlikely that a larger cohort of adolescent donors will be described, nor one that has been followed for so long and so comprehensively. We are less confident than the authors, however, in concluding that adolescent donors are not at higher medical risk due to the small sample size and the nature of the control group. We agree with the authors that this paper should not be seen as endorsing the routine use of adolescent living donors, as the major concern with using donors in this age group has always been their ability to provide adequate informed consent to donate. If it could be definitively shown that an adolescent donor has the same long-term risks as an adult donor, this would add to the information available for pretransplant counseling, but concerns with limited capacity to interpret and act on that information would remain. There is a chance that this information may actually add to coercion of adolescent donors, as donation that is seen as “safe” may rob reluctant teens of a chance to “back out” gracefully. While concerns with coercion are not limited to the adolescent donor, they may be magnified in this situation, because adolescent donors are likely members of the potential recipient’s family and are more likely to be emotionally and financially dependent on those urging
320
them to donate. While this paper may add to the prognostic information that the living donor assessment team is able to provide to an adolescent, it cannot solve the consent and coercion issues that can arise. When an adolescent presents as a potential living donor, teams should continue to apply the criteria of the US Live Organ Donor Consensus group and the American Academy of Pediatrics Committee on Bioethics (as outlined in the MacDonald paper). Only if those criteria are met, should the transplant evaluation proceed, and it is then that this paper can help teams in counseling the potential adolescent donor and his or her family about the long-term risks of donating. A. Goldberg1 and L. Storsley2 1 Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada 2 Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada E-mail: [email protected]
References 1. MACDONALD D, KUKLA A, JACKSON S, et al. Medical outcomes of adolescent live kidney donors. Pediatric Transplantation 2014: 18: 336–341. 2. MJØEN G, HALLAN S, HARTMANN A, et al. Long-term risks for kidney donors. Kidney Int 2013: doi: 10.1038/ki.2013.460. 3. MUZAALE AD, MASSIE AB, WANG MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA 2014: 311: 579–586. 4. DANNENBERG AL, GARRISON RJ, KANNEL WB. Incidence of hypertension in the Framingham Study. Am J Pub Health 1988: 78: 676–679.
