Abstract:

Succinate， the only metabolite that directly links the tricarboxylic acid cycle to the mitochondrial respiratory chain， acts not only as a core substrate for cellular energy metabolism but also as a critical signaling molecule that regulates key biological processes including immunity， post-translational modification， inflammation， and tumorigenesis. Physiological concentrations of succinate are indispensable for maintaining normal renal function. In multiple acute and chronic kidney diseases， succinate levels are consistently upregulated. This accumulated succinate activates the succinate receptor， which in turn triggers the renin-angiotensin-aldosterone system or downstream signaling cascades that modulate energy metabolism， mitochondrial homeostasis， oxidative stress， renal tubular epithelial cell apoptosis， phenotypic transition， and macrophage M2 polarization. Additionally， succinate accumulation regulates T cell-mediated immune responses and HIF-1α signaling. Collectively， these molecular events promote the development of tubulointerstitial injury， inflammation， and fibrosis. Furthermore， both urinary and circulating succinate levels are significantly correlated with disease progression， indicating its promising potential as a clinically applicable diagnostic and prognostic biomarker. Preclinical studies have confirmed that interventions targeting succinate accumulation and its downstream effector pathways exert significant renoprotective effects， opening new avenues for the development of novel therapeutic strategies for kidney diseases. This review summarizes the biological roles and underlying mechanisms of succinate， its potential as a disease biomarker， and current intervention strategies targeting succinate in the context of kidney disease， with the aim of providing novel insights for the identification of new therapeutic targets for kidney diseases.

Key words: succinate, kidney disease, SUCNR1