A new cell culture model for polycystic kidney disease

Abstract

The polycystic kidney disease (PKD) constitutes one of the most frequent and potentially fatal hereditary or acquired disorders of the human kidney. It affects 1 in 1.000 individuals and perhaps five million people worldwide, making PKD more common than other genetically transmitted diseases like cystic fibrosis, muscular dystrophy or sickle cell anemia. PKD is the fourth leading cause of chronic renal failure and accounts for fifteen per cent of patients requiring renal transplantation or dialysis. The disease is characterized by the formation of numerous cystic expansions and the progression of renal epithelium due to tubular dysmorphogenesis. The presence of renal cysts in affected individuals constantly increases with age and approaches hundred per cent of patients by the age of eighty. The progressive increase in the amount and size of cysts is thought to be responsible for subsequent renal failure. The mechanism of cyst formation and growth remains largly unknown but has been attributed to enhanced cell proliferation, accumulation of fluid in the nascent cyst due to mislocation of membran proteins (e.g. Na⁺/K⁺-ATPase), unbalanced cell death and extensive changes in the basal membrane or extracellular matrix of cyst lining epithelial cells. The observation that the product of the recently identified mutated PKD1 gene, which is found in approximately 85% of cases of autosomal dominant PKD, is localized to the extracellular matrix strengthens the hypothesis that the proliferative and secretory abnormalities are likely to be secondary effects and suggests that PKD is an epigenetic disorder. However, there is no treatment that prevents the abnormal formation and enlargement of renal cysts. To further elucidate the nature of PKD and to test potentially useful drugs several animal models have been developed, but a recently described mutant strain of Sprague Dawley rats exhibiting autosomal dominant PKD (Han:SPRD/cy⁺) most closely resembles the human disease.