Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Nephrol Dial Transplant. 2018 Jan 1;33(1):177-184. doi: 10.1093/ndt/gfx281.
This study aimed to analyze adult kidney transplant recipients (KTRs) for the risk of new-onset diabetes after transplantation (NODAT) associated with viral serologies and immunosuppression regimens [tacrolimus (Tac) + mycophenolate (MPA), cyclosporine (CSA) + MPA, sirolimus (SRL) + MPA, SRL + CSA or SRL +Tac].
Cox regression models were used to examine the risk of NODAT in the first posttransplant year associated with: (i) CSA + MPA, SRL + MPA, SRL + MPA or SRL + Tac versus reference, Tac + MPA; (ii) pretransplant viral serology [+ or -; hepatitis B core (HBc), hepatitis C (HCV), cytomegalovirus (CMV) or Epstein Barr Virus (EBV)]; and (iii) interactions between immunosuppression regimens and the viral serology found significant in the main analysis.
Adult KTRs (n = 97 644) from January 1995 through September 2015 were studied. HCV+ [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.31-1.68] or CMV+ (HR 1.12, 95% CI 1.06-1.19) serology was a risk factor and HBc+ (HR 1.04, 95% CI 0.95-1.15) or EBV+ (HR 1.06, 95% CI 0.97-1.15) serology was not a risk factor for NODAT. Regardless of associated HCV or CMV serology, risk of NODAT relative to the reference regimen (Tac + MPA) was lower with CSA + MPA [HCV-: HR 0.74, 95% CI 0.65-0.85; HCV+: HR 0.47, 95% CI 0.28-0.78; CMV-: CSA + MPA HR 0.68, 95% CI 0.54-0.86; CMV+: (CSA + MPA) HR 0.73, 95% CI 0.63-0.85] and similar with SRL + CSA or SRL + MPA. In KTRs with HCV- or CMV+ serology, SRL + Tac was associated with a higher risk of NODAT relative to reference [HCV- (HR 1.43, 95% CI 1.17-1.74) and CMV+ (HR 1.44, 95% CI 1.14-1.81), respectively]. The risk for NODAT-free graft loss was lower with Tac + MPA than the other regimens.
Tailoring immunosuppression regimen based on HCV or CMV serology may modify the risk of developing NODAT in KTRs.
本研究旨在分析成人肾移植受者（KTR）在移植后新发糖尿病（NODAT）的风险，与病毒血清学和免疫抑制方案有关[他克莫司（Tac）+吗替麦考酚酯（MPA）、环孢素（CSA）+MPA、西罗莫司（SRL）+MPA、SRL+CSA 或 SRL+Tac]。
Cox 回归模型用于研究与以下因素相关的移植后第一年 NODAT 风险：（i）CSA+MPA、SRL+MPA、SRL+MPA 或 SRL+Tac 与参照方案 Tac+MPA 相比；（ii）移植前病毒血清学[+或-；乙型肝炎核心（HBc）、丙型肝炎（HCV）、巨细胞病毒（CMV）或 EBV]；以及（iii）在主要分析中发现免疫抑制方案和病毒血清学之间存在交互作用的情况。
研究对象为 1995 年 1 月至 2015 年 9 月的成人 KTR（n=97644）。HCV+[风险比（HR）1.50，95%置信区间（CI）1.31-1.68]或 CMV+（HR 1.12，95% CI 1.06-1.19）血清学是一个风险因素，而 HBc+（HR 1.04，95% CI 0.95-1.15）或 EBV+（HR 1.06，95% CI 0.97-1.15）血清学不是 NODAT 的风险因素。无论相关的 HCV 或 CMV 血清学如何，与参照方案（Tac+MPA）相比，CSA+MPA 的 NODAT 风险较低[HCV-：HR 0.74，95% CI 0.65-0.85；HCV+：HR 0.47，95% CI 0.28-0.78；CMV-：CSA+MPA HR 0.68，95% CI 0.54-0.86；CMV+：（CSA+MPA）HR 0.73，95% CI 0.63-0.85]，而 SRL+CSA 或 SRL+MPA 则相似。在 HCV-或 CMV+血清学的 KTR 中，与参照相比，SRL+Tac 与 NODAT 风险增加相关[HCV-（HR 1.43，95% CI 1.17-1.74）和 CMV+（HR 1.44，95% CI 1.14-1.81）]。与其他方案相比，Tac+MPA 使 NODAT 无移植肾丢失的风险降低。
根据 HCV 或 CMV 血清学调整免疫抑制方案可能会改变 KTR 发生 NODAT 的风险。
