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

ADPKD and ARPKD are a significant cause of morbidity and mortality in children and young adults. ADPKD with an incidence of 1:400–1,000 affects over 13 million individuals worldwide, and is a major cause of end-stage renal disease (ESRD) 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 have led to the discovery that abnormal ADPKD and ARPKD gene products interact to create “polycystin" complexes” located at multiple sites within affected cells. The integrated signaling of such complexes leads to abnormal cellular proliferation, altered cellular transport, and abnormal matrix-vascular biology. This review will focus on the molecular and cellular basis of the abnormal cystic phenotype, and review the clinical translation of such basic data into new therapies, which promise to alter the natural history of disease for children with genetic PKDs.