Pathophysiology of childhood polycystic kidney diseases: new insights into disease-specific therapy

Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are significant causes of morbidity and mortality in children and young adults. ADPKD, with an incidence of 1:400 to 1:1,000, affects more than 13 million individuals worldwide and is a major cause of end-stage renal disease in adults. However, symptomatic disease is increasingly recognized in children. ARPKD is a dual-organ hepatorenal disease with an incidence of 1:20,000 to 1:40,000 and a heterozygote carrier rate of 1 in 70. Currently, no clinically significant disease-specific therapy exists for ADPKD or ARPKD. The genetic basis of both ADPKD and ARPKD have been identified, and delineation of the basic molecular and cellular pathophysiology has led to the discovery that abnormal ADPKD and ARPKD gene products interact to create “polycystin complexes” located at multiple sites within affected cells. The extracellular matrix and vessels produce a variety of soluble factors that affect the biology of adjacent cells in many dynamic ways. This review will focus on the molecular and cellular bases of the abnormal cystic phenotype and discuss the clinical translation of such basic data into new therapies that promise to alter the natural history of disease for children with genetic PKDs.