Broadening horizons in mechanisms, management, and treatment of diabetic kidney disease. (April 2023)

• Record Type: Journal Article
• Authors: Petrazzuolo, Adriana; Sabiu, Gianmarco; Assi, Emma; Maestroni, Anna; Pastore, Ida; Lunati, Maria Elena; Montefusco, Laura; Loretelli, Cristian; Rossi, Giada; Ben Nasr, Moufida; Usuelli, Vera; Xie, Yanan; Balasubramanian, Hari Baskar; Zocchi, Monica; El Essawy, Basset; Yang, Jun; D'Addio, Francesca; Fiorina, Paolo
• Is Part Of: Pharmacological research. Volume 190(2023)
• Publication Date: 2023-04
• Subjects: Diabetic kidney disease -- Diabetes -- Podocytes -- Glomerular cells; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2023.106710
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Diabetic kidney disease (DKD) is the first cause of end-stage kidney disease in patients with diabetes and its prevalence is increasing worldwide. It encompasses histological alterations that mainly affect the glomerular filtration unit, which include thickening of the basement membrane, mesangial cell proliferation, endothelial alteration, and podocyte injury. These morphological abnormalities further result in a persistent increase of urinary albumin-to-creatinine ratio and in a reduction of the estimated glomerular filtration rate. Several molecular and cellular mechanisms have been recognized, up to date, as major players in mediating such clinical and histological features and many more are being under investigation. This review summarizes the most recent advances in understanding cell death mechanisms, intracellular signaling pathways and molecular effectors that play a role in the onset and progression of diabetic kidney damage. Some of those molecular and cellular mechanisms have been already successfully targeted in preclinical models of DKD and, in some cases, strategies have been tested in clinical trials. Finally, this report sheds light on the relevance of novel pathways that may become therapeutic targets for future applications in DKD. Graphical Abstract: ga1