New-onset diabetes after kidney transplantation: can the risk be modified by choosing immunosuppression regimen based on pretransplant viral serology?

Background: 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].

Methods: 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.

Results: 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.

Conclusions: Tailoring immunosuppression regimen based on HCV or CMV serology may modify the risk of developing NODAT in KTRs.