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Published on: May 7, 2019
Hepatitis C and renal transplantation in the era of modern immunosuppression
Kevin C Abbott1, Jay R Bucci, Cal S Matsumoto
1Nephrology Service, Walter Reed Army Medical Center (WRAMC), Washington, DC 20307, USA. kevin.abbott@na.amedd.army.mil
Insights
Kidneys from hepatitis C virus-positive donors (DHCV+) increase mortality risk after kidney transplants. Modern immunosuppression and comorbidities do not alter this independent risk, highlighting the need for careful patient selection.
Area of Science:
- Nephrology
- Transplantation Immunology
- Infectious Diseases
Background:
- Hepatitis C virus-positive donor kidneys (DHCV+) are a known risk factor for mortality post-renal transplant.
- The persistence of this risk with modern immunosuppression and after adjusting for cardiac comorbidities remains unclear.
Purpose of the Study:
- To determine if DHCV+ is an independent risk factor for mortality after renal transplantation, considering modern immunosuppression and baseline cardiac comorbidity.
- To evaluate the impact of mycophenolate mofetil on survival in DHCV+ recipients.
Main Methods:
- Historical cohort study of 36,956 US adult cadaveric renal transplant recipients (1996-2001).
- Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss.
- Adjustments were made for comorbid conditions and dialysis access complications.
Main Results:
- DHCV+ was independently associated with a significantly increased risk of mortality (aHR, 2.12; P < 0.001), primarily due to infection.
- Mycophenolate mofetil use was linked to improved survival in DHCV+ patients, mainly by reducing infectious deaths.
- This association persisted across subgroups, including HCV-positive, HCV-negative, elderly recipients, and those on mycophenolate mofetil.
Conclusions:
- DHCV+ remains an independent risk factor for increased mortality after renal transplantation, even after adjusting for baseline comorbidities.
- Recipients of DHCV+ organs are at high risk, potentially due to the need for intensified immunosuppression.
- Careful consideration of donor and recipient factors is crucial for optimizing transplant outcomes.
Abstract:
Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.
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