Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany.
Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
Sci Rep. 2016 Aug 30;6:32273. doi: 10.1038/srep32273.
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.
免疫抑制是肾移植(RTx)后 BK 病毒肾病(BKVN)的主要危险因素。由于个体他克莫司(Tac)代谢率与 Tac 副作用相关,我们假设 Tac 代谢也可能影响 BKV 感染风险。在这项病例对照研究中,将 RTx 后 4 年内发生 BK 病毒血症的 RTx 患者(BKV 组)与 BKV 阴性对照组进行比较。采用血药浓度与日剂量比值(C/D 比值)来评估 Tac 代谢率。在 RTx 后中位时间 6(0-36)个月时,86 例患者出现 BK 病毒血症。BKV 阳性患者在 RTx 后 1、3 和 6 个月时 Tac C/D 比值较低,被归类为快速 Tac 代谢者。8 例 BK 病毒血症患者中有 8 例经组织学证实存在 BKN,其最大病毒载量中位数高于无 BKN 的 BKV 患者(441,000 拷贝/ml 比 18,572 拷贝/ml)。我们从数据中得出结论,快速 Tac 代谢(C/D 比值<1.05)与 RTx 后 BK 病毒血症有关。在 RTx 后早期计算 Tac C/D 比值,可能有助于移植临床医生识别高危患者,并选择最佳免疫抑制方案。