INVESTIGATING RENAL FUNCTION MODULATION IN CHRONIC KIDNEY DISEASE: INSIGHTS INTO PATHOPHYSIOLOGY AND THERAPEUTIC TARGETS

Abstract

Chronic kidney disease (CKD) is a progressive disorder characterized by persistent structural or functional renal abnormalities that impair filtration, tubular regulation, metabolic balance, and endocrine activity. Its increasing global burden is associated with aging, diabetes, hypertension, obesity, vascular disease, cardiovascular complications, and high healthcare costs. Renal function decline in CKD is not uniform; it reflects complex interactions among glomerular hemodynamic stress, tubular dysfunction, neurohormonal activation, oxidative injury, mitochondrial impairment, inflammation, vascular pathology, and fibrotic remodeling. Renal function modulation provides an integrated framework for understanding how residual nephron activity, albuminuria, renal blood flow, tubular transport, and structural remodeling influence disease progression. Key pathogenic mechanisms include glomerular hyperfiltration, podocyte injury, maladaptive tubular repair, renin–angiotensin–aldosterone system activation, immune-mediated injury, metabolic reprogramming, and renal fibrosis. Biomarkers such as estimated glomerular filtration rate, serum creatinine, cystatin C, albuminuria, tubular injury markers, inflammatory mediators, fibrosis markers, and omics-based signatures are increasingly important for risk prediction and therapeutic monitoring. Current and emerging interventions, including blood pressure control, RAAS blockade, sodium–glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, glucagon-like peptide-1 receptor agonists, anti-inflammatory agents, anti-fibrotic strategies, mitochondrial therapies, and precision nephrology approaches, may slow CKD progression. This review highlights pathophysiological mechanisms and therapeutic targets relevant to preserving renal function and delaying kidney failure.