Nephrotoxicity in Diabetes and Obesity: Mechanisms, Biomarkers, and Therapeutic Interventions

Diabetes and obesity, two closely interlinked metabolic disorders, have emerged as major drivers of chronic kidney disease (CKD) and nephrotoxicity worldwide. Beyond hemodynamic and metabolic stressors, these conditions generate a milieu of hyperglycemia, lipotoxicity, oxidative stress, and low-grade systemic inflammation that progressively damage renal parenchyma. Nephrotoxicity in this context is multifactorial, encompassing glomerular injury, tubulointerstitial fibrosis, endothelial dysfunction, and altered renal drug handling. Immune and metabolic crosstalk further amplify renal vulnerability, with adipokines, advanced glycation end-products, and pro-inflammatory cytokines fueling maladaptive repair responses. This review synthesizes current knowledge on the molecular mechanisms underlying nephrotoxicity in diabetes and obesity, with emphasis on oxidative stress pathways, mitochondrial dysfunction, immune dysregulation, and renin–angiotensin–aldosterone system (RAAS) activation. Emerging biomarkers including proteomic and metabolomic signatures, urinary extracellular vesicles, and novel tubular stress markers are discussed in relation to early detection and risk stratification. Finally, therapeutic interventions are highlighted, ranging from lifestyle and metabolic correction to pharmacologic strategies such as SGLT2 inhibitors, GLP-1 receptor agonists, RAAS modulators, and novel anti-inflammatory or antifibrotic agents. Understanding the intersection of diabetes, obesity, and nephrotoxicity is essential for developing precision approaches to prevention and therapy in high-risk populations.