Afsar Baris, Afsar Rengin Elsurer, Demiray Atalay, Altay Sevval, Korkmaz Hakan, Yildiz Abdulmecit, Covic Adrian, Ortiz Alberto, Kanbay Mehmet
Department of Medicine, Division of Nephrology, Suleyman Demirel University School of Medicine, Isparta, Turkey.
Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.
Clin Kidney J. 2022 Jan 31;15(7):1275-1283. doi: 10.1093/ckj/sfac029. eCollection 2022 Jul.
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease. Recent evidence suggests that the pathogenesis of ADPKD is a complex web of abnormal cellular processes including altered cell signaling, disordered cell metabolism, impaired autophagy, increased apoptosis, mitochondrial dysfunction and chronic inflammation. Sodium-glucose cotransporter (SGLT) inhibitors (SGLTi) reduce body weight, blood pressure and blood glucose levels, have kidney and cardiovascular protective activity, and have been reported to decrease inflammation, increase autophagy and improve mitochondrial dysfunction. We now review results from preclinical studies on SGLTi for ADPKD identified through a systematic search of the MEDLINE, Cochrane Library, Embase and PubMed databases. Potential underlying mechanisms for the conflicting results reported as well as implications for clinical translation are discussed, as ADPKD patients were excluded from clinical trials exploring kidney protection by SGLT2 inhibitors (SGLT2i). However, they were not excluded from cardiovascular safety trials or trials for cardiovascular conditions. A post-hoc analysis of the kidney function trajectories and safety of SGLT2i in ADPKD patients enrolled in such trials may provide additional information. In conclusion, SGLT2i are cardio- and nephroprotective in diverse clinical situations. Currently, it is unclear whether ADPKD patients may benefit from SGLT2i in terms of kidney function preservation, and their safety in this population remains unexplored. We propose a roadmap to address this unmet clinical need.
常染色体显性多囊肾病（ADPKD）是最常见的遗传性肾病。最近的证据表明，ADPKD的发病机制是一个复杂的异常细胞过程网络，包括细胞信号改变、细胞代谢紊乱、自噬受损、细胞凋亡增加、线粒体功能障碍和慢性炎症。钠-葡萄糖协同转运蛋白（SGLT）抑制剂（SGLTi）可减轻体重、降低血压和血糖水平，具有肾脏和心血管保护活性，并且据报道可减轻炎症、增加自噬并改善线粒体功能障碍。我们现在回顾通过系统检索MEDLINE、Cochrane图书馆、Embase和PubMed数据库确定的关于SGLTi治疗ADPKD的临床前研究结果。讨论了所报道的相互矛盾结果的潜在潜在机制以及对临床转化的影响，因为ADPKD患者被排除在探索SGLT2抑制剂（SGLT2i）肾脏保护作用的临床试验之外。然而，他们并未被排除在心血管安全性试验或心血管疾病试验之外。对此类试验中纳入的ADPKD患者的SGLT2i肾功能轨迹和安全性进行事后分析可能会提供更多信息。总之，SGLT2i在多种临床情况下具有心脏和肾脏保护作用。目前，尚不清楚ADPKD患者在肾功能保存方面是否可能从SGLT2i中获益，并且其在该人群中的安全性仍未得到探索。我们提出了一条路线图来满足这一未满足的临床需求。
