Human beings are living longer. According to the Centers for Disease Control, the average life expectancy of a 65-year-old in 1960 was 14 years. By 2016, that figure increased to 20 years.1 In addition, the incidence of end-stage renal disease (ESRD) in patients over the age of 65 years has more than tripled in the last 30 years (from 300 per million/y in 1980 to 1400 per million/y in 2016).2,3 Against this background, it has become commonplace for transplant providers to evaluate increasingly older candidates for kidney transplantation. Many studies have shown that, even among the elderly, kidney transplantation improves both quality and quantity of life of patients when compared with those who are waitlisted but remain on dialysis.4,5
ESRD following a previous nonkidney solid organ transplant (nkSOT) has been steadily increasing as a reason for waitlisted patients for kidney transplantation. In this issue of Transplantation, Haugen et al6 use retrospective registry data from the Scientific Registry of Transplant Recipients (SRTR), which includes data on all donors, waitlisted candidates, and transplant recipients in the United States, submitted by the members of Organ Procurement and Transplantation Network, to ask whether the otherwise well-known survival benefit of kidney transplantation applies to one select group of elderly patients (≥65 y of age at the time of listing for a kidney transplantation) who have had a prior nkSOT (either liver [n = 478], heart [n = 387], or lung [n = 65] transplantation). Among the 5023 study subjects meeting these criteria between 1995 and 2016, 930 (18.5%) received a kidney transplant during the period of study. Interestingly, this rate of transplantation among waitlisted patients is about the same as overall rate for older waitlisted patients.7
Compared with aged patients who received a kidney transplant with no prior history of nkSOT, patients with a prior nkSOT had shorter exposures to dialysis and were more likely to receive preemptive kidney transplants and/or transplants from living donors. Although these factors usually are associated with better graft and patient survivals, the morality rate among patients with prior nkSOTs was actually higher than that of those with a prior nkSOT. While the higher mortality is intuitive given the history of major organ failure vintage, reasons for this is not explored by studying causes of death. The authors attribute this higher mortality rate to “decreased physiologic reserve” and a higher rate of co-morbidities in patients with prior nkSOT, although neither of these factors seem evident from the presented database. In the more important analyses, the authors demonstrate a significant survival benefit when patients with prior nkSOTs and a subsequent kidney transplant are compared with those with prior nkSOTs who remain on the waiting list. Those who received a kidney transplant lived longer: median survival improved from 3.8 years to 7.5 years with kidney transplant (adjusted hazards ratio: 0.47, 95% CI 0.42-0.54) in patients who are waitlisted but not yet transplanted. Female gender, African American race, and, not surprisingly, shorter time on waitlist were associated with less likelihood of receiving kidney transplant. In addition, the survival benefit seemed to be the same across all nkSOT regardless of the type of prior nkSOT. The survival benefit persisted after adjustment for other clinical factors, including age at listing, gender, race, ABO blood type, panel reactive antibody level, diabetes, and time on dialysis. This finding is consistent with well-known observation of kidney transplant improving survival compared with waitlist, even in the elderly population. Limitations of the SRTR database made it impossible for the authors to compare elderly patients receiving kidney transplants after prior nkSOT with another potentially important control group, that is, patients with a prior nkSOT and ESRD, who never get waitlisted for a kidney transplant—presumably because they are considered not to be candidates for kidney transplantation. A potential data source to explore this relationship is United States Renal Data System, which contains nearly all data about patients diagnosed and treated for ESRD in the United States.
At the very least, results of the study by Haugen et al indicate that there is no disadvantage in offering kidney transplants to elderly patients with prior nkSOTs, presumably after appropriate medical evaluation that is standard for any kidney transplant candidate. In fact, within the limits of a retrospective study, their results suggest a modest survival benefit—at least compared with similar patients who have not yet received transplants. This study adds to previously published studies indicating that, with all other things being equal (including recipient age and the presence or absence of a prior nkSOT), it is virtually always better to get a kidney transplant than staying on dialysis and not getting one.4,5 Understanding the benefit of kidney transplantation in older patients with prior nkSOT may be helpful to transplant providers in counseling such patients during their evaluations. However, additional studies are necessary to assess quality of life in this unique population of patients and to determine at what time point posttransplant the survival benefit outweighs the risk of death. Further research also is needed to determine when the risks of kidney transplantation after a prior nkSOT outweigh the benefits to an extent that would make kidney transplantation inadvisable. Finally, considering that patients receiving a kidney transplant after a prior nkSOT are likely exposed to large cumulative amounts of immunosuppression, it would be of interest to know the causes of death in this patient population. Are they similar to other elderly transplant recipients with high rates of death from infection and malignancy? Or is it possible that reduced cardiovascular mortality, compared with that observed in waitlisted patients, accounts for the observed survival benefit?
4. Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.N Engl J Med1999341231725–1730
5. Oniscu GC, Brown H, Forsythe JL. How old is old for transplantation?Am J Transplant20044122067–2074
6. Haugen CE, Luo X, Holscher CM, et al. Outcomes in older kidney transplant recipients after prior non-kidney transplants.Transplantation20191032383–2387
7. Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2016 Annual Data Report: Kidney.Am J Transplant201818Suppl 118–113