Diagnosis of Autosomal-Dominant Polycystic Kidney Disease: An Integrated Approach

SummaryAutosomal-dominant polycystic kidney disease (ADPKD) is the most common Mendelian disorder of the kidney and accounts for approximately 5% of end-stage renal disease in developed countries. It is characterized by focal and sporadic development of renal cysts that increase in number and size with age. Mutations of 2 genes (ie, PKD1 and PKD2) account for most of the cases. Although the clinical manifestations of both gene types overlap completely, PKD1 is associated with more severe disease than PKD2, with bigger kidneys and earlier onset of end-stage renal disease. In general, the diagnosis of ADPKD is commonly made by renal ultrasonography. Age-dependent ultrasound criteria have been established for both diagnosis and disease exclusion in subjects at risk of PKD1. However, the utility of these criteria in the clinic setting is unclear because their performance characteristics have not been defined for the milder PKD2 and the gene type for most test subjects is unknown. Recently, highly predictive ultrasound diagnostic criteria have been derived for at-risk subjects of unknown gene type. In addition, molecular genetic testing is now available for the diagnosis of ADPKD, especially in subjects with equivocal imaging results, with a negative or indeterminate family history, or in younger at-risk individuals with a negative ultrasound study being evaluated as potential living-related kidney donor. Here, we review the clinical utilities and limitations of these imaging- and molecular-based diagnostic tests, and outline our approach for the evaluation of individuals suspected to have ADPKD.