Abimereki D. Muzaale

Perioperative Mortality and Long-term Survival Following Live Kidney Donation

CONTEXT More than 6000 healthy US individuals every year undergo nephrectomy for the purposes of live donation; however, safety remains in question because longitudinal outcome studies have occurred at single centers with limited generalizability. OBJECTIVES To study national trends in live kidney donor selection and outcome, to estimate short-term operative risk in various strata of live donors, and to compare long-term death rates with a matched cohort of nondonors who are as similar to the donor cohort as possible and as free as possible from contraindications to live donation. DESIGN, SETTING, AND PARTICIPANTS Live donors were drawn from a mandated national registry of 80 347 live kidney donors in the United States between April 1, 1994, and March 31, 2009. Median (interquartile range) follow-up was 6.3 (3.2-9.8) years. A matched cohort was drawn from 9364 participants of the third National Health and Nutrition Examination Survey (NHANES III) after excluding those with contraindications to kidney donation. MAIN OUTCOME MEASURES Surgical mortality and long-term survival. RESULTS There were 25 deaths within 90 days of live kidney donation during the study period. Surgical mortality from live kidney donation was 3.1 per 10,000 donors (95% confidence interval [CI], 2.0-4.6) and did not change during the last 15 years despite differences in practice and selection. Surgical mortality was higher in men than in women (5.1 vs 1.7 per 10,000 donors; risk ratio [RR], 3.0; 95% CI, 1.3-6.9; P = .007), in black vs white and Hispanic individuals (7.6 vs 2.6 and 2.0 per 10,000 donors; RR, 3.1; 95% CI, 1.3-7.1; P = .01), and in donors with hypertension vs without hypertension (36.7 vs 1.3 per 10,000 donors; RR, 27.4; 95% CI, 5.0-149.5; P < .001). However, long-term risk of death was no higher for live donors than for age- and comorbidity-matched NHANES III participants for all patients and also stratified by age, sex, and race. CONCLUSION Among a cohort of live kidney donors compared with a healthy matched cohort, the mortality rate was not significantly increased after a median of 6.3 years.

Risk of End-Stage Renal Disease Following Live Kidney Donation

IMPORTANCE Risk of end-stage renal disease (ESRD) in kidney donors has been compared with risk faced by the general population, but the general population represents an unscreened, high-risk comparator. A comparison to similarly screened healthy nondonors would more properly estimate the sequelae of kidney donation. OBJECTIVES To compare the risk of ESRD in kidney donors with that of a healthy cohort of nondonors who are at equally low risk of renal disease and free of contraindications to live donation and to stratify these comparisons by patient demographics. DESIGN, SETTINGS, AND PARTICIPANTS A cohort of 96,217 kidney donors in the United States between April 1994 and November 2011 and a cohort of 20,024 participants of the Third National Health and Nutrition Examination Survey (NHANES III) were linked to Centers for Medicare & Medicaid Services data to ascertain development of ESRD, which was defined as the initiation of maintenance dialysis, placement on the waiting list, or receipt of a living or deceased donor kidney transplant, whichever was identified first. Maximum follow-up was 15.0 years; median follow-up was 7.6 years (interquartile range [IQR], 3.9-11.5 years) for kidney donors and 15.0 years (IQR, 13.7-15.0 years) for matched healthy nondonors. MAIN OUTCOMES AND MEASURES Cumulative incidence and lifetime risk of ESRD. RESULTS Among live donors, with median follow-up of 7.6 years (maximum, 15.0), ESRD developed in 99 individuals in a mean (SD) of 8.6 (3.6) years after donation. Among matched healthy nondonors, with median follow-up of 15.0 years (maximum, 15.0), ESRD developed in 36 nondonors in 10.7 (3.2) years, drawn from 17 ESRD events in the unmatched healthy nondonor pool of 9364. Estimated risk of ESRD at 15 years after donation was 30.8 per 10,000 (95% CI, 24.3-38.5) in kidney donors and 3.9 per 10,000 (95% CI, 0.8-8.9) in their matched healthy nondonor counterparts (P < .001). This difference was observed in both black and white individuals, with an estimated risk of 74.7 per 10,000 black donors (95% CI, 47.8-105.8) vs 23.9 per 10,000 black nondonors (95% CI, 1.6-62.4; P < .001) and an estimated risk of 22.7 per 10,000 white donors (95% CI, 15.6-30.1) vs 0.0 white nondonors (P < .001). Estimated lifetime risk of ESRD was 90 per 10,000 donors, 326 per 10,000 unscreened nondonors (general population), and 14 per 10,000 healthy nondonors. CONCLUSIONS AND RELEVANCE Compared with matched healthy nondonors, kidney donors had an increased risk of ESRD over a median of 7.6 years; however, the magnitude of the absolute risk increase was small. These findings may help inform discussions with persons considering live kidney donation.

Living Kidney Donors Ages 70 and Older: Recipient and Donor Outcomes

BACKGROUND AND OBJECTIVES The profound organ shortage has resulted in longer waiting times and increased mortality for those awaiting kidney transplantation. Consequently, patients are turning to older living donors. It is unclear if an upper age limit for donation should exist, both in terms of recipient and donor outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In the United States, 219 healthy adults aged ≥70 have donated kidneys at 80 of 279 transplant centers. Competing risks models with matched controls were used to study the independent association between older donor age and allograft survival, accounting for the competing risk of recipient mortality as well as other transplant factors. RESULTS Among recipients of older live donor allografts, graft loss was significantly higher than matched 50-to 59-year-old live donor allografts (subhazard ratio [SHR] 1.62, 95% confidence interval [CI] 1.16 to 2.28, P = 0.005) but similar to matched nonextended criteria 50-to 59-year-old deceased donor allografts (SHR 1.19, 95% CI 0.87 to 1.63, P = 0.3). Mortality among living kidney donors aged ≥70 was no higher than healthy matched controls drawn from the NHANES-III cohort; in fact, mortality was lower, probably reflecting higher selectivity among older live donors than could be captured in National Health and Nutrition Examination Survey III (NHANES-III; HR 0.37, 95% CI 0.21 to 0.65, P < 0.001). CONCLUSIONS These findings support living donation among older adults but highlight the advantages of finding a younger donor, particularly for younger recipients.

Patterns of End-Stage Renal Disease Caused by Diabetes, Hypertension, and Glomerulonephritis in Live Kidney Donors.

Inferences about late risk of end‐stage renal disease (ESRD) in live kidney donors have been extrapolated from studies averaging <10 years of follow‐up. Because early (<10 years) and late (≥10 years) postdonation ESRD may differ by causal mechanism, it is possible that extrapolations are misleading. To better understand postdonation ESRD, we studied patterns of common etiologies including diabetes, hypertension and glomerulonephritis (GN; as reported by providers) using donor registry data linked to ESRD registry data. Overall, 125 427 donors were observed for a median of 11.0 years (interquartile range 5.3–15.7 years; maximum 25 years). The cumulative incidence of ESRD increased from 10 events per 10 000 at 10 years after donation to 85 events per 10 000 at 25 years after donation (late vs. early ESRD, adjusted for age, race and sex: incidence rate ratio [IRR] 1.31.72.3 [subscripts are 95% confidence intervals]). Early postdonation ESRD was predominantly reported as GN‐ESRD; however, late postdonation ESRD was more frequently reported as diabetic ESRD and hypertensive ESRD (IRR 2.37.725.2 and 1.42.64.6, respectively). These time‐dependent patterns were not seen with GN‐ESRD (IRR 0.40.71.2). Because ESRD in live kidney donors has traditionally been reported in studies averaging <10 years of follow‐up, our findings suggest caution in extrapolating such results over much longer intervals.

Quantifying Postdonation Risk of ESRD in Living Kidney Donors

Studies have estimated the average risk of postdonation ESRD for living kidney donors in the United States, but personalized estimation on the basis of donor characteristics remains unavailable. We studied 133,824 living kidney donors from 1987 to 2015, as reported to the Organ Procurement and Transplantation Network, with ESRD ascertainment via Centers for Medicare and Medicaid Services linkage, using Cox regression with late entries. Black race (hazard ratio [HR], 2.96; 95% confidence interval [95% CI], 2.25 to 3.89; P<0.001) and male sex (HR, 1.88; 95% CI, 1.50 to 2.35; P<0.001) was associated with higher risk of ESRD in donors. Among nonblack donors, older age was associated with greater risk (HR per 10 years, 1.40; 95% CI, 1.23 to 1.59; P<0.001). Among black donors, older age was not significantly associated with risk (HR, 0.88; 95% CI, 0.72 to 1.09; P=0.3). Greater body mass index was associated with higher risk (HR per 5 kg/m2, 1.61; 95% CI, 1.29 to 2.00; P<0.001). Donors who had a first-degree biological relationship to the recipient had increased risk (HR, 1.70; 95% CI, 1.24 to 2.34; P<0.01). C-statistic of the model was 0.71. Predicted 20-year risk of ESRD for the median donor was only 34 cases per 10,000 donors, but 1% of donors had predicted risk exceeding 256 cases per 10,000 donors. Risk estimation is critical for appropriate informed consent and varies substantially across living kidney donors. Greater permissiveness may be warranted in older black candidate donors; young black candidates should be evaluated carefully.

A smartphone app for increasing live organ donation

The incidence of live donor transplantation has declined over the past decade, and waitlisted candidates report substantial barriers to identifying a live donor. Since asking someone to donate feels awkward and unfamiliar, candidates are hesitant to ask directly and may be more comfortable with a passive approach. In collaboration with Facebook leadership (Facebook Inc., Menlo Park, CA), we developed a mobile application—an app—that enables waitlisted candidates to create a Facebook post about their experience with organ failure and their need for a live donor. We conducted a single‐center prospective cohort study of 54 adult kidney‐only and liver‐only waitlisted candidates using the Facebook app. Cox proportional hazards models were used to describe donor referral on behalf of candidates using the app compared with matched controls. The majority of candidates who used the app reported it to be “good” or “excellent” with regard to the installation process (82.9%), readability (88.6%), simplicity (70.6%), clarity (87.5%) and the information provided (85.3%). Compared with controls, candidates using the Facebook app were 2.436.6117.98 times more likely to have a donor come forward on their behalf (p < 0.001). The Facebook app is an easy‐to‐use instrument that enables waitlisted candidates to passively communicate with their social network about their need for a live donor.

Experiences Obtaining Insurance After Live Kidney Donation

The impact of kidney donation on the ability to change or initiate health or life insurance following donation is unknown. To quantify this risk, we surveyed 1046 individuals who donated a kidney at our center between 1970 and 2011. Participants were asked whether they changed or initiated health or life insurance after donation, and if they had any difficulty doing so. Among 395 donors who changed or initiated health insurance after donation, 27 (7%) reported difficulty; among those who reported difficulty, 15 were denied altogether, 12 were charged a higher premium and 8 were told they had a preexisting condition because they were kidney donors. Among 186 donors who changed or initiated life insurance after donation, 46 (25%) reported difficulty; among those who reported difficulty, 23 were denied altogether, 27 were charged a higher premium and 17 were told they had a preexisting condition because they were kidney donors. In this single‐center study, a high proportion of kidney donors reported difficulty changing or initiating insurance, particularly life insurance. These practices by insurers create unnecessary burden and stress for those choosing to donate and could negatively impact the likelihood of live kidney donation among those considering donation.

Outcomes of Live Kidney Donors Who Develop End-Stage Renal Disease.

Background Kidney donors can develop end-stage renal disease (ESRD) after donation, but the outcomes of those who do remain poorly characterized. Methods Using United States Renal Data System and Scientific Registry for Transplant Research data, we compared access to kidney transplantation (KT), time from ESRD to listing, time from listing to KT, and post-KT graft failure and death between donors and matched nondonors with ESRD. Results Among 99 donors between April 1994 and November 2011 who developed ESRD, 78 initially received dialysis (of whom 37 listed for KT, 2 received live donor KT without listing, and 39 never listed for or received a KT), 20 listed preemptively (of whom 19 were subsequently transplanted), and 1 received a preemptive live donor KT without listing or ever receiving dialysis. Donors were listed earlier (median time to listing, 17 months vs 120 for nondonors; P < 0.001), received KT earlier (median waiting time, 2.8 months vs 21.5 for nondonors; P < 0.001), and received 13% live donor, 87% standard criteria, and 0% expanded criteria deceased donor KT (39%, 50%, and 11% in nondonors). Post-KT graft (adjusted hazard ratio, 1.9; 95% confidence interval, 0.9 to 4.1; P = 0.1) and patient (adjusted hazard ratio, 0.7; 95% confidence interval, 0.2 to 2.4; P = 0.5) survival were comparable in donors and nondonors. Conclusions Our finding that 39 of 99 donors who developed ESRD never listed for a transplant warrants further study to ascertain why these donors with ESRD never gained access to the waiting list.

Risk of End‐Stage Renal Disease in HIV‐Positive Potential Live Kidney Donors

New federal regulations allow HIV‐positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end‐stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV‐positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV‐negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV‐positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV‐negative scenarios. For 40‐year‐old HIV‐positive individuals with health characteristics that were similar to those of age‐matched kidney donors, viral load <400 copies/mL, and CD4+ count ≥500 cells/μL, the 9‐year cumulative incidence of ESRD was higher than that of their HIV‐negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV‐positive individuals with no comorbidities and well‐controlled disease may be considered low‐risk kidney donor candidates.

Long-term Renal Function in Living Kidney Donors Who Had Histological Abnormalities at Donation.

Background Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. Methods We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Results Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5-8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73 m2 decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (P < 0.01). Conclusions In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, whereas no other subclinical histological abnormalities provided additional information.