Metformin suppresses calcium oxalate crystal-induced kidney injury by promoting Sirt1 and M2 macrophage-mediated anti-inflammatory activation
Haoran Liu, Chen Duan, Xiaoqi Yang, Jianhe Liu, Yaoliang Deng, Hans‐Göran Tiselius, Zhangqun Ye, Tao Wang, Jinchun Xing, Hua Xu
Abstract
Kidney stones are one of the most common clinical diseases in urology. Approximately 80% of renal calculi are composed of calcium oxalate (CaOx) crystals, which are gradually deposited in the medullary collecting duct or in the renal interstitium, causing nephrocalcinosis. 1 Although CaOx nephrocalcinosis is usually asymptomatic, it can also induce severe inflammation and necrosis of renal tubular epithelial cells (TECs). Necrotic TECs release various damage-associated molecular patterns (DAMPs), which induce renal necroinflammation by activating Toll-like receptor 4 (TLR4) and secreting IL-1β, which triggers proinflammatory M1 macrophages (M1Mϕs) and then amplifies CaOx-induced renal injury, 2 which can induce further crystal deposition and eventually lead to end-stage renal disease. 3 However, information on the pharmacotherapeutics of kidney crystal formation remains limited. In addition, numerous studies have shown that CaOx crystal-induced oxidative stress and inflammatory injury to TECs are vital factors in the progression of crystalline nephropathy. 4 Therefore, putting renal inflammation under control is expected to alleviate CaOx-induced inflammatory responses and inflammation-related tubular cell injury.