Ethnic Disparity in Kidney Transplantation Outcomes: Influence of Donor andRecipient Characteristics

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Racial/Ethnic Disparity in Kidney Transplantation Outcomes: Influence of Donor and Recipient Characteristics Eyob Feyssa, MD, MPH; Charlotte Jones-Burton, MD; Gary Ellison, PhD; Benjamin Philosophe, MD, PhD; Charles Howell, MD

Objective: The purpose of this study was to evaluate the basis for the racial/ethnic disparity in kidney allograft survival. Methods: We conducted a retrospective study of 2130 patients who underwent kidney transplantation between January 1995 and December 2003. Patient and graft survivals were compared using Kaplan-Meier analysis. Results: Black recipients were more likely than white recipients to have hepatitis C infection (24.6% vs 7.1%), current tobacco use (21.2% vs 13.1%), previous alcohol use (22.6% vs 9.7%), and past illicit drug use (13.6% vs 3.9%). Current employment was less common among blacks. Additionally, black recipients were more likely to have a prior kidney transplant (16.7% vs 11.0%) and to have a cadaver kidney donor (74% vs 56.5%). The 5-year allograft survival rate was 72% for whites and 59% for blacks (p < .01). Previous kidney transplantation, cadaveric donor, donor age, recipient employment status, and recipient tobacco use were associated with allograft survival in a Cox proportional hazard model. Conclusions: Graft survival rate in black kidney transplant recipients is significantly lower than whites, and this disparity can be partially explained by the low rate of live donors and a higher previous transplantation rate in blacks. Key words: race/ethnicity n racial disparities n survival n kidney n transplantation n tobacco J Natl Med Assoc. 2009;101:111-115 Author Affiliations: University of Maryland School of Medicine, Departments of Medicine (Drs Feyssa, Jones-Burton, Ellison, and Howell) and Surgery (Dr Philosophe), Baltimore, Maryland. Corresponding Author: Charles D. Howell, MD, 22 S Greene St N3W50, Baltimore, MD 21201 ([email protected]).

Introduction

K

idney transplantation offers better long-term survival than chronic hemodialysis in end-stage renal disease (ESRD) patients.1 The unadjusted 10-year patient survival probability after the first kidney transplant is 59.3% for deceased donor kidney recipients and 75.5% for live donor kidney recipients compared to JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION

only 9.7% for patients who remain on hemodialysis.2 Several donor and recipient factors influence graft and patient survival after kidney transplantation, including the severity of comorbid conditions, donor type, histocompatibility, and waiting time before transplantation. In addition, for reasons that are not entirely clear, graft survival after kidney transplantation is significantly influenced by the race and ethnicity of the recipient. For example, kidney graft survival is significantly lower in black American recipients compared to white recipients. Despite remarkable improvement in care of kidney transplant patients during the past 20 years, the survival difference between blacks and whites has persisted.3-6 Strategies to reduce the outcomes of racial/ethnic disparity in kidney transplantation require a better understanding of responsible factors. The purpose of this study was to measure allograft survival rates between black and white kidney transplant recipients and to determine the recipient and donor factors that contribute to the difference in allograft survival.

Material and Methods Study Design We conducted a retrospective cohort study of 2130 renal transplant recipients (899 black and 1231 white Americans) who underwent kidney transplantation with or without simultaneous pancreas transplantation at University of Maryland Transplant Surgery Center between January 1995 and December 2003. Eighty-one patients from other racial/ethnic groups who received a kidney transplant during the same time interval were excluded from the analysis. Kidney graft and patient survival were study end points. Graft survival time in months was determined by calculating the time between the date of transplantation and the date graft loss was diagnosed or the date of patient death, whichever came first. Patient survival time was assessed from the date of transplantation to the date patient died. The following recipient variables were analyzed: race, gender, age, employment status, cause and duration of ESRD, health behaviors VOL. 101, NO. 2, FEBRUARY 2009 111

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(tobacco smoking, alcohol, and illicit drug use) and hepatitis C (HCV) infection (defined as HCV antibody positive). Transplant-related variables were donor age, donor type (cadaver or live donor), previous history of transplantation, waiting time, causes for graft loss, and death after transplantation. The study was reviewed and approved by the University of Maryland institutional review board.

Statistical Analysis Continuous variables were compared with Student t tests. Categorical variables were analyzed using c2 tests. The cumulative probability of graft and patient survival was estimated using Kaplan-Meier analysis; comparison between the 2 racial/ethnic groups was conducted by means of the log-rank test. In addition, a Cox proportional hazards model was used to evaluate the factors associated with kidney allograft survival. All statistical analysis was performed using the SPSS statistical software for Windows version 11.0 (SPSS, Chicago, Illinois). P < .05 was considered significant.

Results

Table 1 shows demographic and clinical characteristics of kidney transplant recipients by race/ethnic groups. Black recipients were more likely to have hypertension as a cause for ESRD compared to whites, whereas white transplant recipients were more likely to have diabetes mellitus (DM) as a cause of ESRD. Antibody to HCV, current tobacco use, previous alcohol use, and previous illicit drug use were also more common in black recipients. In contrast, employment at the time of transplantation was less common among blacks. No significant difference in gender, mean age, body mass index, and donor age existed between the 2 groups. Blacks were more likely to have a cadaver kidney donor and were less likely to receive a kidney with simultaneous pancreas transplantation. Furthermore, black recipients were more likely to have a history of previous kidney transplantation. Graft and patient outcomes following kidney transplantation are summarized in Table 2. Black recipients had significantly more acute and chronic rejection episodes and were less likely to be alive with a functioning

Table 1. Baseline Recipient Characteristics

Variable Male, n (%) Age, y (mean ± SD) Body mass index, kg/m2 (mean ± SD) Diabetes mellitus as cause of ESRD, n (%) Hypertension as a cause of ESRD, n (%) Alcohol use ever, n (%) Current smoking, n (%) Illicit drug use ever, n (%) Currently employed, n (%) Positive anti-HCV antibody, n (%) Donor age, y (mean ± SD) Cadaveric donor, n (%) Previous kidney transplant, n (%) Median waiting time, m

White N = 1231 752 (61.1) 48.27 ± 13.50 25.60 ± 6.32 527 (43.8) 696 (57.8) 214 (17.4) 161 (13.1) 48 (3.9) 444 (40.0%) 88 (7.1) 40.36 ± 16.12 695 (56.5) 136 (11.0) 8.00

Black N = 899 544 (60.6) 47.44 ± 12.39 26.42 ± 6.53 299 (33.8) 667 (75.5) 275 (30.6) 190 (21.2) 122 (13.6) 216 (26.2%) 221 (24.6) 41.70 ± 16.50 665 (74.0) 150 (16.7) 15.45

P Value NS NS NS < .001 < .001 < .001 < .001 < .001 < .001 < .001 NS < .001 < .01 < .05

Abbreviations: ESRD: end-stage renal disease, HCV: hepatitis C virus, SD: standard deviation

Table 2. Kidney Transplantation Outcomes

Variable Alive and functional graft, n (%)a Acute rejection, n (%)a Chronic rejection, n (%)a Patient death, n (%) (including death with functional kidney) Other, n (%) a

White N = 1231

Black N = 899

946 (76.8) 11 (0.9) 61 (5.0) 144 (11.7)

586 (65.2) 33 (3.7) 115 (12.8) 102 (11.3)

69 (5.6)

63 (7.0)

p < .05 log-rank test

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graft at the end of the study period (p < .05; log-rank test). However, there was no racial/ethnic difference in the percentage of patients who died during the study period as well as in the patient 5-year survival rates (84% for both, p > .05; log-rank test). The mean duration for kidney graft survival was 41.33 ± 29.45 months for whites and 38.14 ± 26.54 for blacks (p < .001). Kaplan-Meier curves for kidney graft survival are presented in Figure 1. Black patients had a significantly lower graft survival rate (p < .001; log-rank test). A previous history of transplantation (p < .001), a cadaver kidney donor (p < .001), employment status (p < .001), donor age (p = .02), recipient age (p = 0.03), and current tobacco use (p = .05) were associated with kidney graft survival in the Cox proportional hazard model. A history of previous kidney transplantation conferred greatest hazard for kidney graft loss (HR, 3.08; 95% confidence interval [CI], 2.54-3.78) followed in decreasing order by cadaver kidney, current tobacco smoking, recipient age > 45 years, and donor age > 45 years (Figure 2). Current employment was associated with a lower probability of graft loss (HR, 0.67; 95% CI, 0.55-0.82). Gender, BMI, alcohol use, drug use, hypertension, DM, HCV, and recipient waiting time were not independent predictors of kidney graft survival.

Discussion

In a single-center study of 2130 kidney transplant recipients between 1995 and 2003, we found signifi-

cantly lower rates of kidney graft survival among black compared to white recipients. The factors associated with kidney graft were previous kidney transplantation, cadaver kidney, current tobacco use, recipient age > 45 years, and donor age > 45 years. Major disparities in health care delivery and outcomes have been observed between black and white patients with ESRD and kidney transplantation.7-9 For example, blacks account for 13% of the general population but for nearly one-third of ESRD population,8,10 yet black recipients have lower patient and graft survival rates following kidney transplantation. A recent review by Young et al concluded that multiple factors operating at different levels of patient care contribute to the racial/ ethnic disparity in kidney transplant outcomes.4 The major factors contributing to decreased access to kidney transplantation include higher rate of comorbidities in black patients and less chance of referral for transplant evaluation. In addition, blacks were less likely to be involved in the medical decision-making process. In previous studies, factors associated with higher rates of graft loss in black kidney transplant recipients have included lower use of live donor kidneys and greater use of cadaver organs, longer waiting times, greater immunological sensitization and higher rates of positive cross-match, and a greater likelihood of incomplete HLA match with the donor.10,11 These factors are associated with an increase in graft loss and higher kidney retransplantation rate, which is a major risk factor

Figure 1. Kaplan-Meier Plot of Unadjusted Graft Survival

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Figure 2. Hazard Ratio for Graft Failure With 95% Confidence Interval

for successive graft loss. In keeping with previous US studies, hypertension and diabetes were the most common causes for ESRD in black and white patients evaluated at the University of Maryland. In addition, blacks were more likely to have hypertension, consistent with its greater prevalence among the black population in the United States. White kidney transplant recipients in the current study had a greater prevalence of DM than did black recipients. This is explained by the much larger number of whites who had a simultaneous pancreas transplantation for ESRD from type 1 DM. We found no significant difference in patient survival between white and black transplant recipients. Similar comparable patient survival has been reported by US Renal Data System and European studies.12 Our study demonstrates a lower graft survival rate in black recipients. However, race/ethnicity was not an independent predictor of graft survival. Black kidney transplant recipients were more likely to have characteristics that were associated with graft loss in the total cohort. This included previous kidney transplantation, cadaver organ donor, tobacco smoking, older donor age, and a lower rate of current employment. A history of previous kidney transplantation was associated with the greatest risk of kidney graft loss in this study. This may explain the higher incidence of acute and chronic rejection among black recipients in the current study. In the United States, the median waiting time for blacks is twice that of whites.10 Black recipients in our study also waited longer for transplantation than whites. However, waiting time was not an independent predictor 114 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION

of patient survival, but receipt of a cadaver organ was significantly associated with 200% increase in risk of kidney graft loss. This finding is consistent with previous reports.11 Indeed 1-year and 5-year graft survival rates were 95% and 78%, respectively, for recipients of living donor kidneys and 83% and 59%, respectively, for recipients of cadaveric kidneys. Current smokers had a significantly higher risk of graft loss compared to nonsmokers. Smoking plays a prominent role in the development of atherosclerotic renal artery, stenosis, and ischemic nephropathy, and increases the rate of renal disease progression, especially in diabetics.4-17 The deleterious effect of tobacco use on kidney graft survival was also observed by Kasiske and Klinger.18 This relation was dose dependent and largely due to an increase in patient mortality. Interestingly, we observed higher patient mortality in the smokers group compared to nonsmokers (13.81% vs 10.51%). However, how tobacco use increases graft loss independent of patient mortality is unknown. Donor age independently predicted graft survival in the present study. Younger donor age (<45 years) was associated with a better graft survival, especially for living donors compared to older donor age. This is consistent with previous published studies.19,20 The difference in graft survival between black and white transplant recipients might be explained in part by variables related to employment status. The majority of blacks were on disability, whereas the majority of whites were working full time at the time of transplantation. Employment can be a surrogate marker to several socioeconomic variables that need to be defined clearly with VOL. 101, NO. 2, FEBRUARY 2009

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respect to kidney transplantation outcomes. Low socioeconomic status as seen with lack of private insurance has been linked with lower graft and patient survival in a prior study.19 In addition, a relation between low family income and graft survival was previously documented.20

CONCLUSION

Graft survival rate in black kidney transplant recipients is significantly lower than whites. This disparity can be partially explained by higher rates of retransplantation, use of cadaver kidney, tobacco use, older donors, and employment (a surrogate for functional status). These results suggest that the racial/ethnic disparity in kidney graft survival can be narrowed by efforts to increase the rate of live kidney donation and reduce tobacco use among black recipients. The impact of socioeconomic variables, including employment status, on graft outcome should be evaluated in future studies.

Acknowledgements

We would like to express our gratitude and appreciation to Pam Campbell, data analyst, Division of Transplantation, University of Maryland, Baltimore, Maryland.

References

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plexity and challenge of renal transplantation in African Americans. Med Clin North Am. 2005;89:1003-1031. 5. Curtis JJ. Kidney transplantation: racial or socioeconomic disparities? Am J Kidney Dis. 1999;34:756-758. 6. Isaacs RB, Nock SL, Spencer CE, et al. Racial disparities in renal transplant outcomes. Am J Kidney Dis. 1999;34:706-712. 7. Qualheim RE, Rostand SG, Kirk KA, et al. Changing patterns of end-stage renal disease due to hypertension. Am J Kidney Dis. 1991;18:336-343. 8. Rostand SG. US minority groups and end-stage renal disease: a disproportionate share. Am J Kidney Dis. 1992;19:411-413. 9. Geiger HJ. Race and health care—an American dilemma? N Engl J Med. 1996;335:815-816. 10. Young CJ, Gaston RS. Renal transplantation in black Americans. N Engl J Med. 2000;343:1545-1552. 11. Young CJ, Gaston RS. African Americans and renal transplantation: disproportionate need, limited access, and impaired outcomes. Am J Med Sci. 2002;323:94-99. 12. Pallet N, Thervet E, Alberti C, et al. Kidney transplant in black recipients: are African Europeans different from African Americans? Am J Transplant. 2005;5:2682-2687. 13. Cosio FG, Alamir A, Yim S, et al. Patient survival after renal transplantation: I. The impact of dialysis pre-transplant. Kidney Int. 1998;53:767-772. 14. Ritz E, Ogata H, Orth SR. Smoking: a factor promoting onset and progression of diabetic nephropathy. Diabetes Metab. 2000;26:S54-S63. 15. Orth SR, Ogata H, Ritz E. Smoking and the kidney. Nephrol Dial Transplant. 2000;15:1509-1511. 16. Orth SR. Smoking—a renal risk factor. Nephron. 2000;86:12-26. 17. Orth SR. Smoking—a risk factor for progression of renal disease. Kidney Blood Press Res. 2000;23:202-204. 18. Kasiske BL, Klinger D. Cigarette smoking in renal transplant recipients. J Am Soc Nephrol. 2000;11:753-759. 19. Butkus DE, Meydrech EF, Raju SS. Racial differences in the survival of cadaveric renal allografts. Overriding effects of HLA matching and socioeconomic factors. N Engl J Med. 1992;327:840-845. 20. Kalil RS, Heim-Duthoy KL, Kasiske BL. Patients with a low income have reduced renal allograft survival. Am J Kidney Dis. 1992;20:63-69. n

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