Angiogenesis and the Pathogenesis of Autosomal Dominant Polycystic Kidney Disease

Occurring with an incidence between 1/400 – 1/1000 live births autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially lethal genetic disorder affecting the kidney (Ecder et al., 2007). The disease results from mutation in either of two genes PKD1, located on chromosome 16p13.3 or PKD2, located on chromosome 4q21 and is inherited in an autosomal dominant manner (European Polycystic Kidney Disease Consortium, 1994; Mochizuki et al., 1996). The resulting disrupted expression of the respective encoded proteins polycystin 1(PC1) and polycystin 2(PC2) leads to development of multiple fluid filled cysts in the kidney. As the cysts continure to grow throughout life the normal kidney parenchyma is gradually lost and ensuing decrease of renal function occurs. ADPKD accounts for 4-10% of end-stage renal disease (ESRD) worldwide (Freedman et al., 2000; Konoshita et al., 1998). In 50% of cases loss of renal function, necessitating renal replacement therapy occurs by age 60 (Gabow et al., 1992). Renal cysts are often evident on ultrasound or magnetic resonance imaging (MRI) in children, who typically do not become symptomatic until reaching young adulthood (Chapman et al., 2003; Fick-Brosnahan et al., 2001; Seeman et al., 2003). While renal cysts are an invariable characteristic of ADPKD, cysts may also occur in other organs with differing degrees of severity. Hepatic cysts are found in 75% of patients with ADPKD by age 60, while pancreatic, arachnoid, seminal vesicle, and prostate cysts occur with a lower frequency (Ecder et al., 2007). ADPKD is a systemic disorder with abnormalities occuring in several organs and a significantly increased risk for cardiovascular complications among affected patients. The reader is referred to several comprehensive reviews on the clinical and and genetic determinants of ADPKD for more detailed description of disease attributes (Chapin & Caplan, 2010; Ecder et al., 2007; Pei, 2011).