Molecular Diagnosis of Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease worldwide, equally affecting all racial groups, with an estimated cumulative lifetime risk of approximately 1 in 1000.¹ In ADPKD, deficiency of polycystin-1 or polycystin-2 leads to the progressive development and growth of kidney cysts and subsequent increase in total kidney volume, regional ischemia, tubular obstruction, and eventually reduced kidney function and end-stage renal disease (ESRD).² Symptoms of ADPKD can include hypertension, urinary concentrating deficits leading to polyuria and nocturia, mass effects leading to chronic discomfort, and acute pain events due to kidney stones, cyst rupture, or infections.³ Extra-renal manifestations of ADPKD can include polycystic liver disease, colonic diverticular disease, hernias, heart valve defects, and intracerebral and aortic aneurysms.³ However, considerable variation in disease severity exists, with some patients experiencing significant symptoms as early as childhood, with other patients not suffering consequences until late in life.⁴ The current gold standard for assessing disease severity and providing kidney disease prognosis is the Mayo Clinic imaging classification that uses magnetic resonance measured height- and age-adjusted total kidney volume (TKV).⁵ However, genetic heterogeneity underlies the phenotypic variability, with over a thousand different mutations now reported, and identification of the responsible mutation can provide concrete evidence of ADPKD, even very early in the disease course.¹