Diabetic nephropathy: pathophysiology, biomarkers and treatment strategies

Diabetic nephropathy (DN) is a major complication of diabetes mellitus and a leading cause of chronic kidney disease and renal failure globally. This review comprehensively summarizes the pathophysiology, biomarkers, and therapeutic strategies of DN. Chronic hyperglycemia and dyslipidemia activate oxidative, inflammatory, fibrotic, and endothelial dysfunction pathways that drive disease progression. Key mediators such as advanced glycation end-products, transforming growth factor-β, protein kinase C, and the renin–angiotensin–aldosterone system contribute to glomerular injury, podocyte loss, and tubulointerstitial fibrosis. Emerging biomarkers, including Neutrophil gelatinase-associated lipocalin, Kidney injury molecule-1, N-acetyl-β-D-glucosaminidase, and podocyte-specific proteins, enable early detection and personalized management. Immune cells (macrophages, lymphocytes) and cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-18) further amplify renal inflammation and damage. Therapeutic interventions such as renin–angiotensin–aldosterone system blockers, sodium-glucose cotransporter-2 inhibitors, and anti-inflammatory or antioxidant agents demonstrate promise in delaying disease progression. This review also highlights recent insights into nanotechnology-based drug delivery and emerging molecular targets that could shape next-generation therapies for DN. Molecular and cellular mechanisms underlying diabetic nephropathy. Hyperglycemia induces oxidative stress, mitochondrial dysfunction, and activation of signaling pathways, including nuclear factor-κB, Janus kinase/signal transducer and activator of transcription, transforming growth factor-β, and protein kinase C. Crosstalk between mesangial, endothelial, and tubular epithelial cells promotes inflammation, extracellular matrix accumulation, and fibrosis.