Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD).
Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD).
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二甲双胍治疗多囊肾病随机试验的初步结果。
DOI：
10.1016/j.kint.2021.06.013
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发表时间：
2021-09
影响因子：
19.6
通讯作者：
Bae KT
中科院分区：
文献类型：
--
作者：
Perrone RD;Abebe KZ;Watnick TJ;Althouse AD;Hallows KR;Lalama CM;Miskulin DC;Seliger SL;Tao C;Harris PC;Bae KT
常染色体显性遗传性多囊肾病（ADPKD）的特征是肾囊肿生长和肾小球滤过率（GFR）下降。在多囊性疾病的临床前模型中发现二甲双胍影响囊肿形成，通常认为是安全的，可能是ADPKD临床研究的有希望的候选药物。在这项为期两年的II期试验中，我们将97例年龄在18-60岁之间、估计GFR超过50 ml/min/1.73 m2的ADPKD患者以1：1的比例随机分配接受二甲双胍或安慰剂，每日两次。主要结果是药物的安全性和耐受性。次要结局包括估计的GFR下降和总肾脏体积增长。38名二甲双胍和39名安慰剂参与者在24个月时仍接受研究产品。二甲双胍组中有21名参与者由于无法耐受而减少了药物剂量，而安慰剂组中有14名参与者（不显著）。两组发生严重不良事件的参与者比例相似。基线时胃肠道症状评定量表评分较低，且随时间推移无显著变化。二甲双胍组GFR估计值的年变化为-1.71，安慰剂组为-3.07 ml/min/1.73 m2/年（平均差异为1.37 {−0.70，3.44} ml/min/1.73 m2），而二甲双胍组身高校正的总肾脏体积的平均年百分比变化为3.87%，安慰剂组为2.16%，（平均差异1.68% {−2.11，5.62}）。因此，发现二甲双胍在ADPKD成人中是安全和可耐受的，同时轻微降低估计的GFR下降，但未达到显著程度。因此，疗效评价需要更大规模的试验，具有足够的把握度来检测终点的差异。
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18–60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m2, in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was −1.71 with metformin and −3.07 ml/min/1.73m2 per year with placebo (mean difference 1.37 {−0.70, 3.44} ml/min/1.73m2), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {−2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints.
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影响因子：
15.9
作者：
Hallows, KR;Raghuram, V;Foskett, JK
通讯作者：
Foskett, JK
影响因子：
5.5
作者：
Hallows, KR;Kobinger, GP;Foskett, JK
通讯作者：
Foskett, JK
影响因子：
82.9
作者：
Rowe I;Chiaravalli M;Mannella V;Ulisse V;Quilici G;Pema M;Song XW;Xu H;Mari S;Qian F;Pei Y;Musco G;Boletta A
通讯作者：
Boletta A
影响因子：
9.8
作者：
Cornec-Le Gall, Emilie;Olson, Rory J.;Harris, Peter C.
通讯作者：
Harris, Peter C.
影响因子：
39.2
作者：
Levey AS;Stevens LA;Schmid CH;Zhang YL;Castro AF 3rd;Feldman HI;Kusek JW;Eggers P;Van Lente F;Greene T;Coresh J;CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
通讯作者：
CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)