Yoshimoto Akira, Morita Yoshifumi, Kume Yukio, Yoshikawa Naoyuki, Ono Yoshikazu, Kurano Makoto, Yatomi Yutaka, Ohkawa Ryunosuke
Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.
Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Biochem Biophys Rep. 2025 Sep 15;44:102264. doi: 10.1016/j.bbrep.2025.102264. eCollection 2025 Dec.
Abnormal reaction curves were observed in urinary creatinine tests in patients with diabetes undergoing metformin therapy. Therefore, we investigated whether metformin interferes with urinary creatinine measurements. First, the reaction curves of urinary creatinine measurements from 328 patients were analyzed, focusing on the maximum reaction speed, final reaction speed, and their ratio. Next, the reaction curves of the creatinine solution with and without metformin were analyzed. To elucidate the mechanism of metformin interference, solutions of creatinine, creatine, sarcosine, and hydrogen peroxide with and without metformin were analyzed using a one-reagent measurement in which reagents 1 and 2 were pre-mixed. As the results, in the 84 patients taking metformin, the maximum reaction speed significantly decreased, whereas the final reaction speed and the ratio of the two speeds significantly increased (p < 0.001). Notably, the area under the curve of the ratio of the two speeds was 0.84 (95 % confidence interval: 0.78-0.89) for detecting metformin use, suggesting that metformin inhibits the series of reactions involved in creatinine measurement and that reaction curve analysis can identify metformin use. Similar results were obtained in experiments using metformin-containing creatinine solutions. Metformin did not interfere with the reactions involving sarcosine or hydrogen peroxide but did interfere with those involving creatinine and creatine, indicating that metformin inhibits creatinase activity. In conclusion, metformin inhibits reactions involved in urinary creatinine measurement in urine samples, potentially leading to falsely low urinary creatinine values and an inaccurate assessment of kidney function in patients with diabetes.
在接受二甲双胍治疗的糖尿病患者的尿肌酐检测中观察到异常反应曲线。因此，我们研究了二甲双胍是否会干扰尿肌酐测量。首先，分析了328例患者尿肌酐测量的反应曲线，重点关注最大反应速度、最终反应速度及其比值。接下来，分析了添加和未添加二甲双胍的肌酐溶液的反应曲线。为了阐明二甲双胍干扰的机制，使用试剂1和试剂2预混合的单试剂测量法分析了添加和未添加二甲双胍的肌酐、肌酸、肌氨酸和过氧化氢溶液。结果显示，在84例服用二甲双胍的患者中，最大反应速度显著降低，而最终反应速度和两种速度的比值显著增加（p<0.001）。值得注意的是，两种速度比值的曲线下面积为0.84（95%置信区间：0.78 - 0.89），用于检测二甲双胍的使用情况，这表明二甲双胍抑制了肌酐测量中涉及的一系列反应，并且反应曲线分析可以识别二甲双胍的使用情况。在使用含二甲双胍的肌酐溶液的实验中也获得了类似的结果。二甲双胍不干扰涉及肌氨酸或过氧化氢的反应，但确实干扰涉及肌酐和肌酸的反应，表明二甲双胍抑制肌酸酶活性。总之，二甲双胍抑制尿样中尿肌酐测量所涉及的反应，可能导致尿肌酐值假性降低，并对糖尿病患者的肾功能评估不准确。
