Pisani Antonio, Riccio Eleonora, Bruzzese Dario, Sabbatini Massimo
Department of Public Health, Chair of Nephrology, University Federico II of Naples, Via Pansini 5, 80131, Naples, Italy.
Department of Public Health, Chair of Statistics, University Federico II of Naples, Naples, Italy.
BMC Nephrol. 2018 Oct 22;19(1):282. doi: 10.1186/s12882-018-1090-3.
Autosomal dominant polycystic kidney disease (ADPKD) accounts for 8-10% of end-stage chronic kidney disease (CKD) patients worldwide. In the last decade, the advanced knowledge in genetics and molecular pathobiology of ADPKD focused some aberrant molecular pathways involved in the pathogenesis of the disease leading to controlled clinical trials aimed to delay its progression with the use of mTOR inhibitors, somatostatin or tolvaptan. Preclinical studies suggests an effective role of metformin in ADPKD treatment by activating AMPK sensor. Clinical trials are currently recruiting participants to test the metformin use in ADPKD patients.
We retrospectively examined the records of our ADPKD patients, selecting 7 diabetic ADPKD patients under metformin treatment and 7 matched non-diabetic ADPKD controls, to test the effect of metformin on renal progression during a 3 year follow-up.
During the first year, the GFR decreased by 2.5% in Metformin Group and by 16% in Controls; thereafter, renal function remained stable in Metformin Group and further decreased in Controls, reaching a 50% difference after 3 years of observation. Accordingly, the overall crude loss of GFR, estimated by a linear mixed model, resulted slower in the Metformin than in Control Group (- 0.9; 95% C.I.: -2.7 to 0.9 vs - 5.0; 95% C.I.: -6.8 to - 3.2 mL/min/1.73 m2 per year, p = 0.002).
Our data are suggestive of a beneficial effect of metformin on progression of ADPKD. Large, randomized, prospective trials are needed to confirm this hypothesis.
常染色体显性遗传性多囊肾病（ADPKD）占全球终末期慢性肾病（CKD）患者的8% - 10%。在过去十年中，ADPKD遗传学和分子病理生物学方面的前沿知识聚焦于该疾病发病机制中一些异常的分子途径，从而开展了旨在使用mTOR抑制剂、生长抑素或托伐普坦延缓其进展的对照临床试验。临床前研究表明二甲双胍通过激活AMPK传感器在ADPKD治疗中发挥有效作用。目前正在招募参与者进行临床试验，以测试二甲双胍在ADPKD患者中的应用效果。
我们回顾性分析了ADPKD患者的病历，选取7例接受二甲双胍治疗的糖尿病ADPKD患者和7例匹配的非糖尿病ADPKD对照，以测试二甲双胍在3年随访期间对肾脏进展的影响。
在第一年，二甲双胍组的肾小球滤过率（GFR）下降了2.5%，对照组下降了16%；此后，二甲双胍组的肾功能保持稳定，而对照组进一步下降，经过3年观察后两组相差50%。因此，通过线性混合模型估计，二甲双胍组GFR的总体粗损失比对照组慢（-0.9；95%置信区间：-2.7至0.9 vs -5.0；95%置信区间：-6.8至-3.2 mL/min/1.73m²每年，p = 0.002）。
我们的数据表明二甲双胍对ADPKD的进展具有有益作用。需要开展大规模、随机、前瞻性试验来证实这一假设。
