Chronic (30 weeks) structural and functional changes were correlated in diphenylthiazole (DPT)-induced polycystic kidney disease (PKD) in rats. DPT induced two different types of progressive tubular changes: cystic transformation and hyperplastic/atrophic tubular changes. Cystic changes diffusely involved collecting tubules in the outer medulla and cortex, and they were progressive over 30 weeks. Hyperplastic/atrophic changes occurred as clusters of tubules in the cortex and involved between 25% and 50% of tubular profiles after 12 and 30 weeks of drug treatment. Thus, the two types of tubular change were independent of each other and represent different cellular responses to the drug. DPT treatment induced no detectable light- and electron-microscopic or histochemical alterations in glomeruli or renal blood vessels. Renal functional changes consisted of: (1) early (4 weeks) and persistent impairment of concentrating ability; (2) a progressive drop in creatinine clearance and elevation in BUN; and (3) the late onset (30 weeks) of moderate proteinuria. These findings suggest that cystic as well as hyperplastic-atrophic tubular changes contribute to the loss of tubular and renal function in DPT-induced PKD. Both types of tubular lesions may have a role in the development of impaired renal function in other forms of experimental and clinical PKD.
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