Mortality and Cardiovascular Disease Among Older (≥55 years) Live Kidney Donors

[Clark]

http://onlinelibrary.wiley.com/doi/10.1111/ajt.12822/abstract

Mortality and Cardiovascular Disease Among Older Live Kidney Donors
P. P. Reese1,2,*, R. D. Bloom1, H. I. Feldman1,2, P. Rosenbaum3, W. Wang4, P. Saynisch4, N. M. Tarsi4, N. Mukherjee4, A. X. Garg5, A. Mussell2, J. Shults2, O. Even-Shoshan4, R. R. Townsend1 andJ. H. Silber4,6
DOI: 10.1111/ajt.12822
American Journal of Transplantation
Early View (Online Version of Record published before inclusion in an issue)

Abstract

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation.

[Clark]

http://onlinelibrary.wiley.com/doi/10.1111/ajt.13016/full

Selecting Appropriate Controls for Kidney Donors
G. Mjøen1,* andH. Holdaas2
DOI: 10.1111/ajt.13016
American Journal of Transplantation
Volume 15, Issue 1, page 286, January 2015

To the Editor

We read with great interest the recent study by Reese et al [1] regarding outcomes in older living donors. Accurate estimates of long-term risks in donors are essential for adequate selection and follow-up. The most important of these is the risk of all-cause mortality.

As in any study concerning long-term survival, the most critical factor is if the control group is healthy enough to serve as comparators for kidney donors. Living kidney donors are thoroughly assessed by physical examination, biochemical testing and radiology. As the authors themselves state [1] such information was not available for the control group. In fact, comorbidities were only ascertained through interviews. This may not have been sufficient.

In this article, the survival curve for all-cause mortality separates immediately after donation in favor of donors. This would imply that, if the groups were indeed similar at baseline, nephrectomy would be associated with an immediate improvement in survival among donors. From what is known about the risks of major surgery and removal of organs, this is not a likely explanation. More likely, the immediate separation of survival curves is due to the fact that the donors are healthier at baseline than the control group.

We suspect that if more information regarding health status at baseline had been available, this would have improved the selection of controls, probably resulting in a healthier control group with better long-term survival. This could have resulted in other survival curves and other conclusions.

The authors conclude at the end of the abstract that “carefully selected older kidney donors do not face a higher risk of death or CVD” (p. 1853). As long as the control group is not also carefully selected, we fear that such a conclusion is premature.

G. Mjøen1,* and H. Holdaas2
*Corresponding author: Geir Mjøen, geir.mjoen@oslo-universitetssykehus.no

[Clark]

http://onlinelibrary.wiley.com/doi/10.1111/ajt.13015/full

Selecting Appropriate Controls for Kidney Donors—Reply
P. P. Reese1,2,*, R. D. Bloom1, H. I. Feldman1,2, A. X. Garg3, A. Mussell2, J. Shults2 andJ. H. Silber4,5
DOI: 10.1111/ajt.13015
American Journal of Transplantation
Volume 15, Issue 1, pages 287–288, January 2015
*Corresponding author: Peter P. Reese, peter.reese@uphs.upenn.edu

To the Editor:

It is not possible to randomize an individual to become a living kidney donor. Therefore, we agree with Mjøen and Holdaas that it is necessary to examine the comparability of the baseline characteristics of the donor and nondonor groups in any study of living donor outcomes [1]. We stand by the conclusion of our manuscript, which reads: “In the context of careful medical evaluation and selection, older donors should expect similar medium-term survival and risk of CVD compared to healthy members of the general population” [2], p. 1859.

Mjøen and Holdaas [1] note that our methods included restriction of the comparison group to nondonors who, in serial interviews with the Health and Retirement Study (HRS), denied a range of relevant health conditions such as diabetes and cardiovascular disease. The HRS participants in the comparison group also needed to rate their overall health as “good,” “very good,” or “excellent.” These were the strategies used to create a nondonor group with a low prevalence of serious medical problems that would serve as a useful benchmark when interpreting outcomes among older live kidney donors. However, we did not have serological values, medical records or abdominal imaging to further characterize the health of the nondonors. Mjøen and Holdaas recapitulated this limitation that we acknowledged in the manuscript, namely the potential for residual confounding by unrecognized medical problems in the nondonor group [2].

Mjøen and Holdaas [1] also draw attention to the separation of the donor and nondonor survival curves in our Figure 2. Yet, that separation was not significant (p = 0.21) in the primary analysis (donors ≥55 years). A substantive conclusion about this study's validity should not be based on this small and statistically insignificant difference in survival, which may only reflect sampling noise.

In Table 1, we present a summary of donor comparison groups from recent studies that reported mortality. The table includes an important study by Mjøen et al that also relied in part on data from interviews to generate a healthy comparison group of nondonors [3]. The table examines whether individuals were excluded from the nondonor groups because of medical abnormalities for which live donors are screened [4]. In each case, the approach taken to assemble the nondonor group has limitations. We hope that future studies will generate new knowledge about long-term donor outcomes using comparison groups that, while likely still imperfect, represent improvements over existing work.

Table 1. Nondonor groups used as comparators in recent studies of outcomes after live kidney donation
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[donor99]

Years ago the half life of a live donor kidney was 20 years based on match...as of 2014 it is 12-15 years....we have polluted the pool. More marginal donors and more marginal recipients (if the recipient is 75 can they have a 20 year half life...if the donor is 70 can it last 20 years??? What do you think?