[Structure and function of the experimental polycystic kidney induced by diphenylthiazole with special reference to...

Autosomal dominant polycystic kidney disease (ADPKD) is one of the major causative diseases leading to renal failure and dialysis treatment. Although the genetic study on the disease has been progressed so far, the initial trigger for cyst formation and several factors enhancing the progression of ADPKD remain to be clarified. Using an animal model of ADPKD, induced by 2-amino-4,5-diphenylthiazole hydrochloride (DPT), we examined the early events in cytogenesis. Especially the role of tubular obstruction in the model in triggering off tubular dilatation was investigated by means of renal micropuncture and tubular microperfusion techniques. Light and electron microscopic studies demonstrated epithelial hyperplasia along collecting ducts after 2 weeks of DPT feeding. In addition, some collecting ducts revealed partial obstruction with hyperplastic cells. Cystic change became prominent over 8 weeks of the treatment. Then micropuncture and microperfusion experiments were performed to measure intratubular pressure in the rats fed DPT for 2-5 weeks (PKD rats) and pair-fed control Sprague-Dawley rats (control rats). Free flow pressure in proximal segments of PKD rats (21.5 +/- 1.0mmHg) was not significantly elevated, as compared with that in control rats (21.3 +/- 1.0mmHg). During the stepwise increments in proximal tubular flow rate, proximal tubular pressure in PKD rats significantly increased especially at higher flow rate, 41.0 +/- 3.6 mmHg in PKD rats and 19.4 +/- 3.1mmHg in control rats (P < 0.01) at 40nl/min. On the other hand, the transit time of loop of Henle was longer in PKD rats (38.9 +/- 2.4 sec) than in control rats (24.9 +/- 0.6 sec, P < 0.01). These results suggest that cyst formation in PKD rats could be preceded by the elevation of tubular resistance, which might be explained by the partial obstruction of collecting ducts. Moreover, these tubular obstruction in the distal segments might be the trigger for the cyst formation in this model.