Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation.

Gerold Thölking,Katharina Schuette-Nuetgen,Iyad Kabar,Raphael Koch,Hermann Pavenstädt,Dirk Pabst,Anna Hüsing,Barbara Suwelack,Christina Schmidt,Heiner Wolters,Stefan Reuter

doi:10.1038/srep32273

Gerold Thölking, Katharina Schuette-Nuetgen + Show 9 more

Open Access

https://doi.org/10.1038/srep32273

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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.

Highlights

While rates of acute rejection (AR) have declined during the last decades due to more effective immunosuppressive regimens[1], BK virus (BKV) infection has become an emerging problem after renal transplantation (RTx)[2]
In the present case-control study 86 patients who developed BKV infection within four years after RTx were compared to 86 BKV negative controls
BKV infection was associated with a fast Tac metabolism at 1 month after RTx

Summary

Introduction

While rates of acute rejection (AR) have declined during the last decades due to more effective immunosuppressive regimens[1], BK virus (BKV) infection has become an emerging problem after renal transplantation (RTx)[2]. We recently showed that fast Tac metabolizers (low C/D ratio) had a reduced renal function 24 months after RTx and 36 months after LTx, respectively[12,13]. This finding might be explained by higher Tac peak levels early after drug intake leading to a higher drug exposure (area under the curve) for these patients. The aim of this study was to analyze whether fast Tac metabolism is a risk factor for BKV infection

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