Venkatasubramanian Vaishnavi, Sethi Jasmine, Kumar Vivek, Yadav Ashok Kumar, Lal Anupam, Kohli Harbir Singh
Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Indian J Nephrol. 2025 May-Jun;35(3):410-416. doi: 10.25259/IJN_100_2024. Epub 2024 Aug 29.
Autosomal dominant kidney disease (ADPKD) is the most common monogenic disorder leading to renal failure with limited therapeutic options. We aimed to assess the efficacy and safety of metformin in nondiabetic ADPKD patients and its role in slowing disease progression.
We conducted a prospective, randomized controlled, open labelled clinical trial and enrolled 52 nondiabetic adults aged 18-60 years with typical ADPKD, estimated glomerular filtration rate (eGFR) > 45 mL/min/m, and no risk factors of rapid disease progression. Participants were randomized in a 1:1 ratio by a computer-generated random number table into metformin + standard of care group (metformin arm) and standard of care group (Control arm). Primary outcome of the study was to evaluate the effects of metformin versus control arm on the percentage and absolute change in eGFR over a 6-month period.
Mean (SD) age of the cohort was 37.15 (10.16) years with half of them being females. The mean (SD) baseline htTKV and eGFR were 335.67 (153.3) mL/m and 100.23 (25.95) mL/min/m, respectively. Clinical exome sequencing was available in nine (17.3%) patients of which two-thirds had PKD1 mutation. Baseline characteristics were distributed equally across randomized groups. Baseline proteinuria was significantly higher in the metformin arm (p = 0.014). The eGFR difference and percentage change in eGFR was not different between the groups at 6 months (p = 0.53 and 0.48, respectively). There was no statistically significant difference in htTKV and percentage change in htTKV at 6 months between the groups, although an increase in htTKV was numerically smaller in the metformin group (p = 0.769, 0.805). Blood pressure, body weight, body mass index (BMI), and proteinuria also did not differ between the two groups. Only half of the cohort tolerated the maximum dose of metformin. Around two-thirds of patients reported adverse effects, most commonly asthenia.
Metformin appears to be safe and well tolerated in nondiabetic patients with ADPKD.
常染色体显性遗传性肾病（ADPKD）是导致肾衰竭的最常见单基因疾病，治疗选择有限。我们旨在评估二甲双胍对非糖尿病性ADPKD患者的疗效和安全性及其在延缓疾病进展中的作用。
我们进行了一项前瞻性、随机对照、开放标签的临床试验，纳入了52名年龄在18至60岁之间的非糖尿病成年人，他们患有典型的ADPKD，估计肾小球滤过率（eGFR）>45 mL/min/m²，且没有疾病快速进展的危险因素。参与者通过计算机生成的随机数字表以1:1的比例随机分为二甲双胍+标准治疗组（二甲双胍组）和标准治疗组（对照组）。该研究的主要结局是评估二甲双胍组与对照组在6个月期间对eGFR百分比和绝对变化的影响。
该队列的平均（标准差）年龄为37.15（10.16）岁；其中一半为女性。平均（标准差）基线总体肾体积（htTKV）和eGFR分别为335.67（153.3）mL/m²和100.23（25.95）mL/min/m²。9名（17.3%）患者进行了临床外显子组测序，其中三分之二有PKD1突变。基线特征在随机分组中分布均匀。二甲双胍组的基线蛋白尿显著更高（p = 0.014）。6个月时，两组之间的eGFR差异和eGFR百分比变化没有差异（分别为p = 0.53和0.48）。两组之间在6个月时的htTKV和htTKV百分比变化没有统计学显著差异，尽管二甲双胍组中htTKV的增加在数值上较小（p = 0.769，0.805）。两组之间的血压、体重、体重指数（BMI）和蛋白尿也没有差异。该队列中只有一半的人耐受二甲双胍的最大剂量。约三分之二的患者报告有不良反应，最常见的是乏力。
二甲双胍在非糖尿病性ADPKD患者中似乎是安全且耐受性良好的。
