Rat models of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 11 Suppl 6

Abstract. Several rat models of polycystic kidney disease (PKD) have been published. The only rat model of autosomal dominant polycystic kidney disease currently used is the so-called Hannover rat (Han:SPRD cy/+). This model is characterized by a slow progression of uraemia, proteinuria and hyper-lipidaemia. Histological changes clearly resemble those seen is human PKD. The localization of Na+/K+-ATPase correlating with the phenotype of the cysts— basal in moderately expanded and apical in highly expanded cysts—suggests that the mislocation of the Na+/K+-ATPase is involved in the mechanism of cyst expansion rather than formation, and a consequence of cell dedifferentiation rather than an initial event. Of note is a considerable gender difference in disease severity. Disease anticipation or genetic imprinting does not occur. In addition to gender, a number of inter-ventions influence the progression rate: acceleration is noted after unilateral nephrectomy, the induction of acidosis, chloride feeding or an increased protein intake; slowing down of the course occurs after the induction of alkalosis and castration, and after treatment with lovastatin and methylprednisolone. Thus the Han:SPRD cy/+ rat represents the only well-documented rat model of autosomal dominant PKD resembling a number of features of the human disease. Key words: genetics; histology; polycystic kidney disease; rat models; uraemi