Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation

Sci Rep. 2016 Aug 30:6:32273. doi: 10.1038/srep32273.

Abstract

Immunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As the individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that Tac metabolism might also influence the BKV infection risk. In this case-control study RTx patients with BK viremia within 4 years after RTx (BKV group) were compared with a BKV negative control group. The Tac metabolism rate expressed as the blood concentration normalized by the daily dose (C/D ratio) was applied to assess the Tac metabolism rate. BK viremia was detected in 86 patients after a median time of 6 (0-36) months after RTx. BKV positive patients showed lower Tac C/D ratios at 1, 3 and 6 months after RTx and were classified as fast Tac metabolizers. 8 of 86 patients with BK viremia had histologically proven BKN and a higher median maximum viral load than BKV patients without BKN (441,000 vs. 18,572 copies/mL). We conclude from our data that fast Tac metabolism (C/D ratio <1.05) is associated with BK viremia after RTx. Calculation of the Tac C/D ratio early after RTx, may assist transplant clinicians to identify patients at risk and to choose the optimal immunosuppressive regimen.

MeSH terms

  • Adult
  • Aged
  • BK Virus / drug effects*
  • BK Virus / physiology
  • Case-Control Studies
  • Female
  • Humans
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Polyomavirus Infections / drug therapy*
  • Polyomavirus Infections / virology
  • Risk Factors
  • Tacrolimus / metabolism
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Tumor Virus Infections / drug therapy*
  • Tumor Virus Infections / virology
  • Viremia / diagnosis
  • Viremia / virology

Substances

  • Immunosuppressive Agents
  • Tacrolimus