Department of Nephrology and Internal Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Department of Urology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Transplantation. 2021 Apr 1;105(4):916-927. doi: 10.1097/TP.0000000000003336.
Mycophenolic acid (MPA) is a standard immunosuppressant in organ transplantation. A simple monitoring biomarker for MPA treatment has not been established so far. Here, we describe inosine 5'-monophosphate dehydrogenase (IMPDH) monitoring in erythrocytes and its application to kidney allograft recipients.
IMPDH activity measurements were performed using a high-performance liquid chromatography assay. Based on 4203 IMPDH measurements from 1021 patients, we retrospectively explored the dynamics early after treatment start. In addition, we analyzed the influence of clinically relevant variables on IMPDH activity in a multivariate model using data from 711 stable patients. Associations between IMPDH activity and clinical events were evaluated in hospitalized patients.
We found that IMPDH activity reflects MPA exposure after 8 weeks of constant dosing. In addition to dosage, body mass index, renal function, and coimmunosuppression affected IMPDH activity. Significantly lower IMPDH activities were found in patients with biopsy-proven acute rejection as compared to patients without rejection (median [interquartile range]: 696 [358-1484] versus 1265 [867-1618] pmol xanthosine-5'-monophosphate/h/mg hemoglobin, P < 0.001). The highest IMPDH activities were observed in hospitalized patients with clinically evident MPA toxicity as compared to patients with hospitalization not related to MPA treatment (1548 [1021-2270] versus 1072 [707-1439] pmol xanthosine-5'-monophosphate/h/mg hemoglobin; P < 0.001). Receiver operating characteristic curve analyses underlined the usefulness of IMPDH to predict rejection episodes (area, 0.662; confidence interval, 0.584-0.740; P < 0.001) and MPA-associated adverse events (area, 0.632; confidence interval, 0.581-0.683; P < 0.001), respectively.
IMPDH measurement in erythrocytes is a novel and useful strategy for the longitudinal monitoring of MPA treatment.
霉酚酸（MPA）是器官移植中标准的免疫抑制剂。目前尚未建立 MPA 治疗的简单监测生物标志物。在这里，我们描述了红细胞中肌苷 5'-单磷酸脱氢酶（IMPDH）的监测及其在肾移植受者中的应用。
使用高效液相色谱法进行 IMPDH 活性测量。基于 1021 名患者的 4203 次 IMPDH 测量，我们回顾性地探讨了治疗开始后早期的动态变化。此外，我们使用 711 名稳定患者的数据，在多变量模型中分析了临床相关变量对 IMPDH 活性的影响。在住院患者中评估了 IMPDH 活性与临床事件之间的关联。
我们发现 IMPDH 活性反映了持续给药 8 周后的 MPA 暴露。除剂量外，体重指数、肾功能和共同免疫抑制也影响 IMPDH 活性。与无排斥反应的患者相比，经活检证实有急性排斥反应的患者的 IMPDH 活性明显较低（中位数[四分位数范围]：696[358-1484]比 1265[867-1618]pmol 黄嘌呤 5'-单磷酸/h/mg 血红蛋白，P<0.001）。与与 MPA 治疗无关的住院患者相比，临床明显 MPA 毒性的住院患者的 IMPDH 活性最高（1548[1021-2270]比 1072[707-1439]pmol 黄嘌呤 5'-单磷酸/h/mg 血红蛋白；P<0.001）。受试者工作特征曲线分析强调了 IMPDH 预测排斥发作（面积，0.662；置信区间，0.584-0.740；P<0.001）和 MPA 相关不良事件（面积，0.632；置信区间，0.581-0.683；P<0.001）的有用性。
红细胞中 IMPDH 的测量是监测 MPA 治疗的一种新颖且有用的策略。
