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Background. The role of renal transplantation as treatment for end-stage sickle cell nephropathy (SCN) has not been well established. Methods. We performed a comparative investigation of patient and allograft outcomes among age-matched African-American kidney transplant recipients with ESRD as a result of SCN (n=82) and all other causes (Other-ESRD, n=22,565). Results. The incidence of delayed graft function and predischarge acute rejection in SCN group (24% and 26%) was similar to that observed in the Other-ESRD group (29% and 27%). The mean discharge serum creatinine (SCr) was 2.7 (± 2.5) mg/dl in the SCN recipients compared to 3.0 (± 2.5) mg/dl in the Other-ESRD recipients (P=0.42). There was no difference in the 1-year cadaveric graft survival (SCN: 78% vs. Other-ESRD : 77%), and the multivariable adjusted 1-year risk of graft loss indicated no significant effect of SCN (relative risk [RR]=1.39, P=0.149). However, the 3-year cadaveric graft survival tended to be lower in the SCN group (48% vs. 60%, P=0.055) and their adjusted 3-year risk of graft loss was significantly greater (RR=1.60, P=0.003). There was a trend toward improved survival in the SCN transplant recipients compared to their dialysis-treated, wait-listed counterparts (RR=0.14, P=0.056). In comparison to the Other-ESRD (RR=1.00), the adjusted mortality risk in the SCN group was higher both at 1 year (RR=2.95, P=0.001) and at 3 years (RR=2.82, P=0.0001) after renal transplantation. Conclusions. The short-term renal allograft result in recipients with end-stage SCN was similar to that obtained in other causes of ESRD, but the long-term outcome was comparatively diminished. There was a trend toward better patient survival with renal transplantation relative to dialysis in end-stage SCN.