PATHOPHYSIOLOGICAL AND MOLECULAR MECHANISMS OF RENAL DYSFUNCTION IN URETERAL STONE-INDUCED OBSTRUCTION

Abstract

Ureteral stone-induced obstruction is one of the most common causes of obstructive nephropathy and may lead to progressive deterioration of renal function. The pathological processes associated with urinary tract obstruction are not limited to the mechanical impairment of urine flow but also involve complex hemodynamic, cellular, and molecular alterations. Increased intrapelvic pressure results in a reduction of glomerular filtration rate, decreased renal blood flow, and tissue hypoxia. Under hypoxic and ischemic conditions, activation of the renin–angiotensin–aldosterone system, oxidative stress pathways, NF-κB-mediated inflammatory responses, and TGF-β1/Smad signaling occurs. These processes contribute to tubular epithelial cell injury, epithelial–mesenchymal transition, excessive extracellular matrix deposition, and the development of tubulointerstitial fibrosis. Progressive fibrosis is associated with nephron loss and the subsequent development of chronic kidney disease. Early detection of ureteral stones and timely relief of obstruction remain essential for preserving renal function. A comprehensive understanding of the molecular mechanisms involved in obstructive nephropathy may facilitate the development of novel pathogenetically targeted therapeutic strategies.