Key points in the Diagnosis of Autosomal Dominant Polycystic Kidney Disease

The diagnosis of ADPKD is most often obtained by ultrasonography. Given that detection rates are less than 85% for individuals and that ultrasonography positively identifies >98% at risk individuals by age 30, imaging has remained the primary diagnostic approach. The presence of enlarged kidneys with multiple cysts is required for the diagnosis of ADPKD. Age-specific, ultrasound-based diagnosis guidelines for ADPKD have been developed, primarily for PKD1-related disease. These same guidelines are less reliable sensitive for PKD2-related disease, in which a later age of onset occurs. In young individuals with PKD2 alterations who undergo screening, there is an increased likelihood of false-negative results by ultrasonography. The presence of two cysts in each kidney in an at-risk individual younger than 30 years is 99% specific and sensitive for the presence of ADPKD. For those older than 30 years and younger than 60 years, four cysts bilaterally in an at-risk individual (i.e., someone with a known affected parent) are necessary for the same level of diagnostic precision. For those older than 60 years, more than eight cysts bilaterally are needed for a positive diagnosis. In the 10% to 15% of ADPKD individuals who do not have a family history, stricter criteria are required for a diagnosis, and at least five cysts bilaterally by the age of 30 and a phenotype consistent with ADPKD must be present.
A negative ultrasound result in an at-risk individual at age 20 years reduces the likelihood of disease inheritance to below 10% and at age 30 years to below 5%. When disease status must be determined with greater certainty (i.e., during evaluation of a potential donor for living, related transplantation), computed tomography (CT) or magnetic resonance imaging (MRI) and genetic testing may be required.
Mutation screening using direct sequencing of the PKD1 or PKD2 genes is commercially available. Direct sequencing is the most accurate and reliable screening method, but expense is a limiting factor. After a genetic diagnosis is made, other at-risk family members can be screened at reduced cost by performing exon-specific sequencing of the identified mutation. Current mutation detection rates in known affected individuals for PKD2 and PKD1 are 95% and 75%, respectively.