Abstract and Introduction
Abstract
Reports of kidney transplantation (KTX) in recipients with hepatitis C virus (HCV+), human immunodeficiency virus (HIV+) or coinfection often do not provide adequate adjustment for donor risk factors. We evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one kidney was transplanted into a patient with viral infection (HCV+, n = 1700; HIV+, n = 243) and the other transplanted into a recipient without infection (HCV− n = 1700; HIV− n = 243) using Scientific Registry of Transplant Recipients data between 2000 and 2013. On multivariable analysis (adjusted for recipient risk factors), HCV+ conferred increased risks of death-censored graft survival (DCGS) (adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.04–1.47) and patient survival (aHR 1.24, 95% CI 1.06–1.45) compared with HCV−. HIV+ conferred similar DCGS (aHR 0.85, 95% CI 0.48–1.51) and patient survival (aHR 0.80, 95% CI 0.39–1.64) compared with HIV−. HCV coinfection was a significant independent risk factor for DCGS (aHR 2.33; 95% CI 1.06, 5.12) and patient survival (aHR 2.88; 95% CI 1.35, 6.12). On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection. Whereas KTX in HIV+ recipients were associated with similar outcomes relative to noninfected recipients, HCV monoinfection and, to a greater extent, coinfection were associated with poor patient and graft survival.
Introduction
Kidney transplantation (KTX) of patients with hepatitis C virus (HCV+) and human immunodeficiency virus (HIV+) has been shown to confer a long-term survival advantage over dialysis and, therefore, is considered the treatment of choice for most end-stage renal disease (ESRD) patients with viral infection.
Despite a survival advantage over dialysis, reports of outcomes among kidney transplant recipients with HCV+ compared to those without hepatitis C virus (HCV−) are often conflicting. Whereas many studies have shown a detrimental effect of HCV+ on kidney transplant graft survival relative to HCV− recipients, others have not found a difference. Interpretation of many of these reports is limited by various methodological issues. In some studies the definition of graft loss also included recipient death or did not specify. Others are limited by very small sample sizes of HCV+ cohorts. Finally, some lack evaluation of and/or adjustment for potential confounding recipient and donor risk factors of graft failure.
Another clinical challenge in managing kidney transplant recipients with HCV is coinfection with HIV (HCV+/HIV+). Hepatitis C may share the same route of transmission as HIV; therefore, coinfection is common with nearly 30% of those with HIV also infected with hepatitis C. Hepatitis C progresses more rapidly in coinfected patients and the higher risk of rejection in HIV+ kidney transplant recipients might require more potent immunosuppression either as prophylaxis against or as treatment of rejection, which may in turn further exacerbate hepatitis C infection and posttransplant liver disease. Additionally, complex interactions between retroviral medications, induction or maintenance immunosuppression, and HCV-mediated effects on liver metabolism contribute to difficult management of drug levels. The published experience is scant regarding the potential deleterious impact of HCV coinfection on the outcome of KTX in HIV+ recipients. Additionally, data from existing reports are limited by small sample size, short follow-up and lack of risk-adjusted analyses.
To determine the magnitude of the risks associated with KTX in HCV+ recipients and HIV+ recipients and to investigate the impact of viral coinfection, we analyzed national registry data for outcomes of adult transplant recipients of kidney pairs. An analysis of mate kidneys from the same donor is optimal to control for the predominant effects of donor quality while illustrating the effects of viral infection.