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二甲双胍日剂量导致急性肾损伤合并乳酸性酸中毒:一例报告。

Daily dose of metformin caused acute kidney injury with lactic acidosis: a case report.

机构信息

Laboratory of Pharmaceutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu, 501-1196, Japan.

Kariya Toyota General Hospital, Aichi, Japan.

出版信息

J Med Case Rep. 2023 Sep 16;17(1):393. doi: 10.1186/s13256-023-04136-0.

Abstract

BACKGROUND

Metformin-induced lactic acidosis with acute kidney injury is rare but well known. Here we report a case of a Japanese patient taking metformin who experienced severe acute renal failure accompanied with significantly elevated metformin plasma concentrations and signs of lactic acidosis.

CASE PRESENTATION

A 60-year-old Japanese man with type II diabetes, who was taking metformin (500 mg three times a day) along with several other medications, visited the emergency department with dizziness, malaise, and oliguria. The initial laboratory test results showed elevated levels of serum creatinine and blood urea nitrogen, although his renal function was normal approximately 2 weeks earlier. His lactate level was raised (4.27 mmol/L), and he was diagnosed with lactic acidosis. Considering the low creatinine clearance and elevated urinary albumin/serum creatinine ratio, urinary N-acetyl-β-D-glucosaminidase level, and β2-microglobulin level, the patient was further diagnosed with AKI (in other words, acute tubular necrosis). A renal biopsy performed on day 3 after admission revealed renal tubular epithelium necrosis, supporting this diagnosis. The patient underwent intermittent hemodialysis until he was discharged on day 13. The metformin concentrations on days 3, 5, and 7 were 8.95, 2.58, and 0.16 μg/mL, respectively, which is significantly higher than the maximal steady-state concentration of metformin at the recommended dosage (approximately 1 μg/mL). The calculated pharmacokinetic parameters of metformin suggested poor renal excretion and a low distribution volume at higher metformin levels. Other possible acute kidney injury-causing factors included dehydration, alcohol consumption, and the use of an angiotensin receptor blocker or SGLT2 inhibitor.

CONCLUSIONS

This is the first reported case of acute kidney injury possibly caused by high levels of metformin with lactic acidosis in a patient treated with the recommended metformin dose. Thus, the development of metformin-induced acute kidney injury should be considered for patients with several acute kidney injury risk factors who are taking metformin.

摘要

背景

二甲双胍引起的乳酸酸中毒伴急性肾损伤虽罕见但广为人知。本文报道了一例日本患者在服用二甲双胍后发生严重急性肾衰竭,同时伴有显著升高的二甲双胍血浆浓度和乳酸酸中毒的迹象。

病例介绍

一位 60 岁的日本男性,患有 2 型糖尿病,正在服用二甲双胍(每天 3 次,每次 500 毫克)和其他几种药物,因头晕、不适和少尿就诊于急诊科。初始实验室检查结果显示血清肌酐和血尿素氮水平升高,尽管大约 2 周前他的肾功能正常。他的乳酸水平升高(4.27mmol/L),被诊断为乳酸性酸中毒。考虑到肌酐清除率低,尿白蛋白/血清肌酐比值、尿 N-乙酰-β-D-氨基葡萄糖苷酶水平和β2-微球蛋白水平升高,患者被进一步诊断为 AKI(即急性肾小管坏死)。入院后第 3 天行肾活检显示肾小管上皮细胞坏死,支持这一诊断。患者接受间歇性血液透析,直至入院后第 13 天出院。入院第 3、5 和 7 天的二甲双胍浓度分别为 8.95、2.58 和 0.16μg/mL,明显高于推荐剂量下的二甲双胍最大稳态浓度(约 1μg/mL)。二甲双胍的药代动力学参数提示在较高的二甲双胍水平下,其肾脏排泄不良,分布容积低。其他可能导致急性肾损伤的因素包括脱水、饮酒以及使用血管紧张素受体阻滞剂或 SGLT2 抑制剂。

结论

这是首例报道的在接受推荐剂量二甲双胍治疗的患者中,因高浓度二甲双胍伴乳酸酸中毒引起的急性肾损伤病例。因此,对于服用二甲双胍且具有多种急性肾损伤风险因素的患者,应考虑发生二甲双胍引起的急性肾损伤的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2c/10504777/ac3105058b7f/13256_2023_4136_Fig1_HTML.jpg

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