Risk of Cause-Specific ESRD in Live Kidney Donors

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http://www.atcmeetingabstracts.com/abstract/risk-of-cause-specific-esrd-in-live-kidney-donors/

Risk of Cause-Specific ESRD in Live Kidney Donors
S. Anjum, A. Muzaale, A. Massie, S. Bae, D. Segev.
2015 American Transplant Congress
Abstract number: 188

The purpose of this study is to investigate the risk of developing cause-specific ESRD in live kidney donors over time.

METHODS: We studied a cohort of 125,451 donors in the United States between 1987-2014 from SRTR data (including left-censored observations before 1994), linked to CMS form 2728. We compared rates of cause-specific ESRD risk using Kaplan-Meier and Poisson regression analyses. Maximum follow-up was 25 years. To compare incidence rate differences, we split this follow-up time into two groups: 0-10 years (era 1) and 10+ years (era 2). We adjusted for age, sex, and race. Age was modeled separately for each era such that the association between older age and risk of disease did not impact the incidence rate ratio models.

RESULTS: Unadjusted cumulative incidence of ESRD was 84 per 10,000 in donors 25 years post-donation (Figure 1). After adjustment, donors in era 2 had a higher incidence rate ratio (3.3 4.4 5. vs. era 1. Similarly, in the diabetes(4.9 17 56)-, hypertension(3.9 7.0 13)-, glomerulonephritis(1.4 2.5 4.4)-, and others(1.9 3.1 5.1)-specific ESRD models, donors have an increased risk of ESRD in era 2 vs. era 1 (Table 1).

CONCLUSIONS: Donor risk for ESRD increases dramatically ten years post donation, particularly diabetes and hypertension specific ESRD (Figure 2).

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http://www.atcmeetingabstracts.com/abstract/risk-of-esrd-attributable-to-live-kidney-donation-in-various-subgroups-of-donors/

Risk of ESRD Attributable to Live Kidney Donation in Various Subgroups of Donors
A. Muzaale, A. Massie, D. Segev.
2015 American Transplant Congress
Abstract number: 636

Risk of ESRD attributable to live donation in male, older, obese, related donors, and donors with high predonation eGFR remains uncharacterized.

Methods: Various subgroups of individuals who donated a kidney between April 1994 and November 2011, and their healthy matched nondonor counterparts identified from NHANES III, were linked to CMS to ascertain the development of ESRD. Risk of ESRD attributable to donation was compared across these subgroups. 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.

Results: Attributable risk of ESRD was substantially higher in male donors (31 per 10,000 male donors vs. 20 per 10,000 female donors), older donors (60 per 10,000 donors aged 60+ vs. 24 per 10,000 donors aged <60years), biologically related donors (27 per 10,000 related donors vs. 14 per 10,000 unrelated donors)(figure 1), obese donors (>80 per 10,000 donors with BMI 30+ vs. 8 per 10,000 donors with BMI <30), and donors with substantial renal reserve (47 per 10,000 donors with eGFR 80+ vs. 6 per 10,000 donors with eGFR <80)(figure 2). However, no substantial difference in attributable risk was observed across blood pressure subgroups (40 per 10,000 related donors vs. 38 per 10,000 donors with SBP<140).

Conclusions: Risk of ESRD attributable to live kidney donation is substantially higher in male, older, obese, related donors, and donors with predonation eGFR>80

Muzaale A, Massie A, Segev D. Risk of ESRD Attributable to Live Kidney Donation in Various Subgroups of Donors [abstract]. Am J Transplant. 2015; 15 (suppl 3). http://www.atcmeetingabstracts.com/abstract/risk-of-esrd-attributable-to-live-kidney-donation-in-various-subgroups-of-donors/. Accessed April 29, 2015.

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http://www.atcmeetingabstracts.com/abstract/long-term-risk-of-esrd-attributable-to-live-kidney-donation-matching-with-healthy-non-donors/

Long-Term Risk of ESRD Attributable to Live Kidney Donation: Matching with Healthy Non-Donors
A. Muzaale, A. Massie, J. Wainright, M. McBride, M. Wang, D. Segev
2013 American Transplant Congress
Abstract number: 565

Background Higher rates of ESRD post-donation have been reported in African-American donors than in white donors, but no studies have compared ESRD incidence in donors to ESRD incidence in comparable non-donors. ESRD risk attributable to donation is unknown.

Methods: We matched a cohort of 96217 live kidney donors (reported to OPTN between 1994-2011) to healthy non-donor controls drawn from the NHANES study, using an incementally expanding radius matching algorithm that we have previously published (JAMA 2010) based on age, gender, race, education, BMI, systolic blood pressure, and smoking history. We then linked both donors and controls to CMS data to obtain ESRD outcomes. Kaplan-Meier curves were used to compare 15-year ESRD incidence, overall and separately among racial/ethnic subgroups. A novel bootstrap method was used to assess statistical significance.

15-year cumulative incidence of ESRD (%)
    Live donors   Matched controls
All races   0.31   0.04
Caucasian   0.23   0.00
African-American   0.75   0.24
Hispanic   0.33   0.07
Results: ESRD incidence at 15 years was 8x higher for live kidney donors (0.31%) than for healthy matched controls (0.04%) (p<0.05, Table 1). Higher incidence was observed among donors than controls in every racial/ethnic group. Both among donors and among controls, African Americans had the highest incidence of ESRD, and Caucasians had the lowest incidence. Fifteen-year incidence was less than one percent among all racial/ethnic subgroups.

Conclusions: Live kidney donors had higher rates of ESRD than matched controls, overall and across racial/ethnic subgroups. However, absolute risk of ESRD within fifteen years of donation is low in all subgroups.

Muzaale A, Massie A, Wainright J, McBride M, Wang M, Segev D. Long-Term Risk of ESRD Attributable to Live Kidney Donation: Matching with Healthy Non-Donors [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://www.atcmeetingabstracts.com/abstract/long-term-risk-of-esrd-attributable-to-live-kidney-donation-matching-with-healthy-non-donors/. Accessed May 2, 2015.

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http://www.atcmeetingabstracts.com/abstract/quantifying-risk-of-esrd-in-live-kidney-donors/

Quantifying Risk of ESRD in Live Kidney Donors
A. Massie, A. Muzaale, X. Luo, D. Segev.
2015 American Transplant Congress
Abstract number: 245

Among live kidney donors higher overall risk of ESRD has been shown in African-Americans and men. However, individual risk of ESRD has not been quantified.

METHODS: We studied risk factors for ESRD (demographics, relatedness to recipient, ZIP code median annual HH income (MAHI), BMI, SBP) in 122,697 live donors using SRTR data and Cox regression. ESRD outcomes 1994-2013 were obtained via CMS linkage; Late entries were used for donors prior to 1994.

RESULTS: Male gender (HR=1.59 2.05 2.64, p<0.001) and African-American (AA) race (HR=2.41 3.29 4.50, p<0.001) were associated with higher risk of ESRD (Table, col 1). Among non-AA donors, older donors had higher incidence of ESRD; however, among AA donors, older donors had lower incidence of ESRD (Figure 1). The race/age interaction was statistically significant (Table, col 1). MAHI<$40K was associated with higher risk (HR=1.04 1.48 2.10, p<0.05); this association partly mediated the race/ESRD association (Table, col 2). Higher BMI was associated with higher risk (Table, col 3). Predicted 20-year risk of ESRD ranged from 13 per 10000 (young non-AA women) to 309 per 10000 (young AA men, Figure 2).

CONCLUSIONS: Older age is associated with greater ESRD risk in non-AA donors, but with lower risk in AA donors, likely due to donor selection. Greater permissiveness may be warranted in older AA donors; younger AA donors should be evaluated carefully and counseled about long-term ESRD risk.

Risk factors of ESRD in live kidney donors
    Model 1 (N=122697)   Model 2 (N=102675)   Model 3 (N=70211)
Male gender   1.59 2.05 2.64   1.38 1.91 2.63   1.04 1.79 3.07
AA race   2.41 3.29 4.50   1.56 2.36 3.57   1.24 2.45 4.86
Age per 10y: non-AA   1.26 1.44 1.65   1.17 1.40 1.66   0.98 1.31 1.75
Age per 10y: AA   0.63 0.79 0.99   0.59 0.80 1.08   0.42 0.71 1.19
unrelated to recipient   0.51 0.76 1.13   0.47 0.73 1.12   0.45 0.83 1.52
MAHI <$40K       1.04 1.48 2.10   0.34 0.68 1.37
BMI per 5 units           1.11 1.46 1.92
SBP per 5 mmHg           0.99 1.09 1.20
bold=p<0.05

Massie A, Muzaale A, Luo X, Segev D. Quantifying Risk of ESRD in Live Kidney Donors [abstract]. Am J Transplant. 2015; 15 (suppl 3). http://www.atcmeetingabstracts.com/abstract/quantifying-risk-of-esrd-in-live-kidney-donors/. Accessed May 2, 2015.

[Clark]

http://www.ncbi.nlm.nih.gov/pubmed/25905980

Transplantation. 2015 Apr 22. [Epub ahead of print]
Race, Relationship and Renal Diagnoses After Living Kidney Donation.
Lentine KL1, Schnitzler MA, Garg AX, Xiao H, Axelrod D, Tuttle-Newhall JE, Brennan DC, Segev DL.

Abstract
BACKGROUND:
In response to recent studies, a better understanding of the risks of renal complications among African American and biologically related living kidney donors is needed.
METHODS:
We examined a database linking U.S. registry identifiers for living kidney donors (1987-2007) to billing claims from a private health insurer (2000-2007 claims) to identify renal condition diagnoses categorized by International Classification of Diseases 9th Revision coding. Cox regression with left and right censoring was used to estimate cumulative incidence of diagnoses after donation and associations (adjusted hazards ratios, aHR) with donor traits.
RESULTS:
Among 4650 living donors, 13.1% were African American and 76.3% were white; 76.1% were first-degree relatives of their recipient. By 7 years post-donation, after adjustment for age and sex, greater proportions of African American compared with white donors had renal condition diagnoses: chronic kidney disease (12.6% vs 5.6%; aHR, 2.32; 95% confidence interval [95% CI], 1.48-3.62), proteinuria (5.7% vs 2.6%; aHR, 2.27; 95% CI, 1.32-3.89), nephrotic syndrome (1.3% vs 0.1%; aHR, 15.7; 95% CI, 2.97-83.0), and any renal condition (14.9% vs 9.0%; aHR, 1.72; 95% CI, 1.23-2.41). Although first-degree biological relationship to the recipient was not associated with renal risk, associations of African American race persisted for these conditions and included unspecified renal failure and reported disorders of kidney dysfunction after adjustment for biological donor-recipient relationship.
CONCLUSIONS:
African Americans more commonly develop renal conditions after living kidney donation, independent of donor-recipient relationship. Continued research is needed to improve risk stratification for renal outcomes among African American living donors.
PMID: 25905980