Periostin in diabetic kidney disease: mechanistic insights, biomarkers, and therapeutic perspectives

Abstract

Diabetic kidney disease (DKD) is among the most common and severe microvascular complications of diabetes and represents a leading cause of end-stage renal disease (ESRD) worldwide. Currently, although strict glycemic and blood pressure control, together with the use of renin–angiotensin system inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and non-steroidal selective mineralocorticoid receptor antagonists, can moderately delay DKD progression, the risks of progression to ESRD and cardiovascular events remain high, highlighting the urgent need to identify novel therapeutic targets. Preclinical and observational studies suggest that periostin (POSTN) is associated with DKD progression and may contribute to renal inflammation and fibrosis. POSTN expression is minimal in healthy kidneys but is markedly upregulated under conditions of renal injury and fibrosis. Cross-sectional clinical studies report that serum, urinary, and renal tissue POSTN levels are elevated in patients with DKD and correlate with proteinuria, the severity of renal fibrosis, and a decline in estimated glomerular filtration rate (eGFR); these associations have not been confirmed prospectively. Preclinical studies indicate that POSTN promotes inflammatory cell infiltration, myofibroblast activation, and extracellular matrix accumulation, and it has therefore been proposed to contribute to the inflammatory and fibrotic progression of DKD. In preclinical DKD models, POSTN inhibition attenuates renal injury and fibrosis. No POSTN-targeted therapy has entered human clinical trials, so POSTN remains a promising preclinical candidate target. This review summarizes the mechanistic basis and recent advances in POSTN research in DKD, and further explores its translational potential as a biomarker and therapeutic target.