The positive impact of kidney transplantation on survival and quality of life of recipients is a dramatic advancement in the care of kidney failure (1, 2). Living donation has the added benefit of a shorter waiting time and increased graft and recipient survival compared with deceased donor transplantation (3, 4). However, the success of the field breeds demand for more organs. The resulting shortage of organs and growing waiting list place inherent pressure on transplant programs to expand the donor pool (5, 6). For African Americans (AA), the shortage of organs is critically important. In particular, AAs suffer from a greater burden of kidney disease and have decreased access to transplantation, including living donor transplantation. Also, AAs experience longer waiting times and inferior graft survival (7). Thus, there is an ever-growing need to find appropriate living donors for AA patients with kidney failure.
Despite the obvious benefits of transplantation and interest in expanding the donor pool, there are inherent risks to living donation. Although short-term risks of surgery are thought to be acceptably low (8, 9), long-term risks are less well characterized (10, 11). Current literature assessing long-term risks of donation do not meet modern evidence-based standards for risk assessment: most studies lack appropriate control groups, definitions of hypertension have changed over time, and studies involve single-center experience with predominantly Caucasian populations. Furthermore, studies were plagued by extensive loss to follow-up (10, 12). These limitations are especially true for the few studies that even mentioned AA donors (13–16). For AAs and donors with isolated medical abnormalities such as obesity and hypertension, the long-term risks are especially unclear (11, 12).
A significant milestone occurred in 2002 upon the publication of a United Network for Organ Sharing/Organ Procurement Transplantation Network (UNOS/OPTN) study noting 56 former donors who subsequently developed kidney failure and were placed on the kidney transplant waiting list (17). Given the greater prevalence of chronic kidney disease and kidney failure in AAs, the lack of long-term safety data in AA living kidney donors remains a critical piece of missing information in providing informed consent and estimating risk.
Currently, donors are not followed and tracked universally, meaning that adverse outcomes are not captured in any systematic way. We sought an indirect way of studying the question of excess risk in African American kidney donors using the UNOS/OPTN database, which awards extra points to wait-listed kidney transplant candidates if they formerly donated a kidney (17). It was our hypothesis that AAs would represent a disproportionate number of these subjects (former donors with kidney failure who entered the kidney transplant waiting list) when comparing this frequency to the proportion of AA in the overall population of living kidney donors.
Information from the UNOS/OPTN registry was obtained on all patients in the United States who were listed for a kidney transplant and who were recorded as being previous kidney donors. All subjects were placed on the waiting list between 1993 and 2005. This represented the time (1996) when UNOS awarded extra points for former kidney donors, with five additional subjects identified between 1993 and 1996 as their first listing, with second listings occurring after 1996. Age, gender, race, cause of end-stage renal disease, reason for removal from the waiting list, and time between donation and listing were sought. Descriptive statistics were generated for patients placed on the waiting list. To compare the frequencies of various races of living donors on the waiting list to their respective frequencies of living donation, we sought information from UNOS on the race of all living donors over the same time period, January 1, 1993, to November 15, 2005. Frequencies were compared by means of chi-square testing. This study did not involve identifiable human subject information.
One hundred two unique individuals were placed on the kidney transplant waiting list. Five patients were listed after a failed allograft but were counted only once as the initial listing occurred prior to 1996. Characteristics of this group appear in Table 1. Mean age was 32 at the time of kidney donation, and 36% were female. Causes of end-stage renal disease (ESRD) included hypertension (n=28), focal segmental glomerulosclerosis (FSGS, n=13), diabetes (n=9), various other glomerular diseases (n=16), failed allograft (n=5), and a group of other diagnoses, including pyelonephritis/reflux (n=2), familial nephropathy (n=2), renal cell carcinoma (n=2), unilateral kidney, gout, trauma, fibromuscular dysplasia, analgesic nephropathy, and parvovirus. For 19 subjects, the diagnosis was listed as unknown. This was a specific diagnosis given by the referring transplant center, who checked “other, specify” and than wrote “unknown” as a diagnosis.
There were 62,327 living donations between 1993 and 2005. Race of donors compared to frequency of donation appears in Table 2. Despite comprising only 14% of 62,327 living donors between 1993 and 2005, AAs represented 44% of those listed for kidney transplant (P<0.001). Caucasians were the majority of living donors (68% of 62,327) but were only 40% of those on the waiting list (P<0.001). For Hispanics, Asians, and Native Americans, frequencies of donation and listing were not significantly different.
Reasons for removal from the waiting list were variable. Only six of the previous donors underwent living donor transplants. A total of 84 received deceased donor transplants, five died or were too sick to transplant, and four were still waiting at the time of this report. The length of time between donation and listing appears in Figure 1. For 20 subjects, these data were not reported. Median time between donation and listing was 17.6 years. The majority of subjects were listed at least 16 years from donation, with 43% listed 16–25 years after donation, and 18% listed >25 years after donation. When the time between donation and listing was “unknown,” the original donation date was not supplied by the transplant center, and the donation occurred prior to 1994 when donor records were available.
Of note, 10 donors were listed less than 5 years after donating a kidney. Nine of ten were AA, with one Caucasian, and six were female. These donors had a mean age of 28.2 years at donation. Causes of ESRD included FSGS (n=2), chronic GN (n=2), hypertension, retransplant, pyelonephritis/reflux, parvovirus B19, and unknown (2).
In this study, we noted that the number of kidney donors who have been placed on the waiting list continues to grow, and that AA are more frequently found on this list than would be expected by their frequency of donation. We also noted a long latent period between donation and listing for the majority of subjects, indicating that there may be a growing number of donors reaching ESRD in future years. Finally, we described a group of predominantly young AA donors who developed kidney failure within 5 years of donation, a group that necessitates further inquiry into young AA donors. Altahough these data are thought provoking and reason for pause, they provide only indirect evidence and generate further questions.
What does this study mean to AA donors? One interpretation is that the increased risk of ESRD seen reflects only the increased risk of ESRD in all AAs and that donation itself played a minimal role. However, even this conclusion implies that the screening process involved in selecting a kidney donor, generally excluding hypertension, proteinuria, severe obesity, and diabetes, fails to erase the increased risk of ESRD in this population. This alone would be a meaningful conclusion. However, if donation itself carries a proportionally greater risk for kidney failure in AAs because of some undescribed effect on GFR, blood pressure, or hyperfiltration injury, than it should give the transplant community reason to consider gathering additional data on AA kidney donors. Regardless, our study is an important step towards the goal of accurate informed consent for AA kidney donors.
Another obvious question: what is the incidence of ESRD after donation? As others have noted (17, 18), this is a simple question that is nearly impossible to answer given the inability to establish a clear numerator (number reaching ESRD) and denominator (total number of U.S. living kidney donors). The problem of a prolonged latent period between donation and ESRD is the greatest obstacle to calculation an absolute incidence, as many of these donors reached the waiting list after a donation that occurred before clear national records became available in 1988. Furthermore, not all patients developing kidney failure will be placed on the waiting list because many will have reached advanced age or have comorbid conditions that will preclude transplantation. Clearly, establishing the incidence of ESRD after donation must include a way of systematically capturing those subjects that never reach the waiting list. However, for AAs, the closest minimum estimate of ESRD risk (44 of nearly 10,000 AA kidney donors between 1988 and 2005) is similar to the estimated point prevalence of ESRD in AA (48 per 10,000) in the general population (19), a figure that is an order of magnitude greater than previous estimates of 3 per 10,000 (0.03%) for all kidney donors (17). As transplant centers continue to evaluate AAs, obese donors, older donors, and even those with controlled hypertension, previous assumptions about the long-term risks of kidney failure will need to be re-examined.
In conclusion, ESRD requiring kidney transplantation continues to be reported in kidney donors, usually many years after donation. For AAs, this risk may be elevated when compared to the risk in subjects of other races. While it is likely that the overall risk of ESRD and wait-listing for transplantation is low, the risks of kidney donation are not well established for African Americans, and the risk of ESRD (including patients not approved for transplant listing) is poorly characterized for all kidney donors. Prospective studies of AA kidney donors are sorely lacking, and more comprehensive tracking of donors for risk of serious adverse outcomes (advanced CKD, ESRD, and death) is needed.
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