Unified ultrasonographic diagnostic criteria for polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening hereditary disease in the United States, occurring in approximately one in every 400 to 1000 live births.1 ADPKD accounts for approximately 5 to 10% of end-stage renal failure in the United States requiring dialysis and renal transplantation.2 ADPKD is characterized by progressive enlargement of cyst-filled kidneys, severely affecting those who inherit one of the known genes that cause the disease. Mutations in PKD1, located on chromosome 16, are associated with a higher prevalence (85% of cases), earlier clinical presentation, and higher morbidity and mortality. Less profoundly affected individuals with mutations in PKD2, located on chromosome 4, account for the remaining 15% of cases.3 In patients with PKD2 mutations, end-stage kidney disease occurs on average 20 yr later than with PKD1 mutations (mean age 74 versus 54 yr).3 In a study previously reported in JASN, PKD1 kidneys were significantly larger and had more cysts than PKD2 kidneys, although the rate of cyst growth was not different between PKD1 and PKD2 kidneys.4 On the basis of effectiveness, cost, and safety, ultrasound is the most commonly used imaging modality to make the diagnosis of ADPKD. Magnetic resonance imaging and computed tomography scanning are used for research purposes, and no reported studies have compared ultrasound with other imaging modalities for the diagnosis of ADPKD. ADPKD is suspected when patients present with symptoms related to the large kidneys associated with hypertension, flank pain or hematuria, palpable kidneys or liver, or subarachnoid hemorrhage. ADPKD is also diagnosed incidentally when an abdominal ultrasound is performed for other reasons, such as pregnancy. When there is no family history of ADPKD, a presumptive diagnosis can be made when there are more than 10 cysts in each kidney and there are no renal or extrarenal findings suggesting another disease that causes renal cyst formation, such as tuberous sclerosis complex, von Hippel-Lindau disease, and acquired cystic disease. Screening for ADPKD is controversial, because the consequences of a positive diagnosis (emotional and insurance issues) need to be weighed against the benefits because effective therapies for humans are not yet proved. Linkage analysis and direct DNA analytic techniques are available for genetic testing for PKD1 and PKD2 genes; however, genetic testing is not routinely performed. Genetic testing is not a useful screening tool because it can identify only approximately 70% of the hundreds of different PKD1 and PKD2 mutations.5 Genetic testing is mainly used for research purposes and to make a definite diagnosis in a potential living-related kidney donor who is younger than 30 yr and does not yet have kidney cysts on ultrasound. Thus, in clinical practice, ultrasound is the major screening and diagnostic tool. Ravine et al.6 established age-dependent ultrasound diagnostic criteria for PKD1. Specifically, in at-risk individuals between 15 and 30 yr of age, at least two unilateral or bilateral kidney cysts; in individuals between 30 and 59 yr of age, two cysts in each kidney; and in individuals older than 60 yr, at least four cysts in each kidney. Because PKD2 mutations result in a milder form of ADPKD, false-negative ultrasound diagnostic results are more likely when screening young patients with PKD2 mutations. When at-risk patients with family histories and renal cysts are seen at the clinic, molecular genotyping is seldom performed and it is not known whether the patients have PKD1 or PKD2 mutations. Thus, the Ravine criteria established for PKD16 that are commonly used to diagnose PKD in patients with a family history but of unknown genotype may be inaccurate. Age-dependent ultrasound diagnostic criteria are needed for evaluating at-risk individuals from families with ADPKD of unknown genotype. More than a decade after the establishment of ultrasound diagnostic criteria for PKD1 by Ravine et al.,6 the article by Pei et al.7 in this issue of JASN evaluates the performance of ultrasound diagnostic criteria in 948 at-risk individuals from families who have PKD1 and PKD2 mutations and underwent molecular genotyping. They found the diagnostic criteria currently used for PKD1 in at-risk patients from 15 to 59 yr of age did not do as well when applied to patients with PKD2 because of a higher risk for false-negative results, which reduced test sensitivity. Thus, new standard diagnostic criteria for patients with ADPKD of unknown genotype are proposed. For patients from families with ADPKD of unknown genotype, the following is sufficient for making the diagnosis: In individuals between 15 and 39 yr of age, the presence of Published online ahead of print. Publication date available at www.jasn.org.