The pathogenesis of drug induced renal cystic disease

Abstract

Oral administration of 2 amino 4,5 diphenyl thiazole HC1 to rats over a period of 11 wk produced marked, diffuse, progressive renal cystic disease without significant tubular obstruction or interstitial fibrosis. Light and electron microscopic and microdissection studies demonstrated that cystic changes began in collecting ducts in the medulla and extended to cortical collecting and distal tubules and loops of Henle. Micropuncture studies on pair fed control animals treated with the drug for 5 wk and on pair fed controls revealed that glomerular function was unaltered and that intratubular pressure and reabsorption of solute and water along proximal convoluted and distal tubules were normal in cystic kidneys. These data indicate that nephrons with cystic change are capable of normal function. In the absence of tubular obstruction, it is proposed that cystic disease was due to a drug induced structural defect of the tubular basement membrane which in the presence of a normal transtubular pressure gradient results in progressive tubular dilatation.