5/6 Nephrectomy as an Experimental Model for Chronic Kidney Disease: New Vasoactive and Antioxidant Therapeutic Targets.

Chronic kidney disease (CKD) is a progressive disorder characterized by declining renal function and increased cardiovascular risk. Experimental models are essential for investigating these mechanisms, and the 5/6 nephrectomy (5/6 Nx) model is widely used to reproduce cardiorenal alterations observed in CKD. This review aims to critically evaluate how effectively the 5/6 Nx model reproduces vasoactive and redox mechanisms relevant for pharmacological testing. A narrative synthesis of experimental studies using the 5/6 Nx model in rodents was performed, focusing on vascular, inflammatory, and oxidative pathways. The 5/6 Nx model reproduces major CKD features, including hypertension, proteinuria, glomerulosclerosis, and cardiovascular remodeling. Early activation of the renin-angiotensin-aldosterone system, endothelin signaling, and sympathetic pathways contributes to vascular dysfunction. Sustained oxidative stress reduces nitric oxide bioavailability and promotes endothelial dysfunction. Dysregulation of natriuretic peptides and increased 20-HETE signaling further contribute to vascular imbalance and remodeling. These alterations occur in a well-defined temporal progression, supporting the use of this model for mechanistic and pharmacological studies. The 5/6 Nx model remains a robust and translationally informative platform for investigating CKD progression, provided that pathway-specific reproducibility and experimental variables are carefully considered.