Polycystic kidney disease: huge kidneys, huge problems, huge progress

Abstract

Polycystic kidney disorders are more common than once appreciated, are contributors to significant morbidity, are potentially fatal and are costly to treat. In the past few years much progress has been made toward understanding the pathogenesis of renal cystic disorders. The dominantly inherited disorders are initiated by mutations within genes located in chromosomes 16 and 4 (ADPKD) that cause the kidneys to enlarge several-fold greater than normal. This enlargement is owing to the proliferation of epithelial cells in tubule segments, to the accumulation of fluid within the dilated tubule segment created by the proliferating cells, and to remodelling of the extracellular matrix. The focal beginning of ADPKD in a relatively few renal tubules suggests that the cells in the walls of cysts may reflect clonal growth and that this aberrant proliferation may be secondary to a somatic "second hit" process. The rate at which the cysts enlarge appears to depend on endocrine, paracrine and autocrine factors that drive cellular proliferation and transepithelial fluid secretion within the cysts. The presence of the renal cysts within certain kidneys appears to provoke interstitial inflammation and apoptosis that contribute to fibrosis and renal insufficiency in approximately one-half of persons with ADPKD. Why renal cysts do not cause renal failure in the other one-half of patients with polycystic kidneys is a provocative question that awaits further study.