Received May 17, 2008
Accepted on July 23, 2008

CLINICAL RESEARCH

Unified Criteria for Ultrasonographic Diagnosis of ADPKD

York Pei ^*1, James Obaji ^*, Annie Dupuis , Andrew D. Paterson , Riccardo Magistroni ^||, Elizabeth Dicks ^¶, Patrick Parfrey ^¶, Benvon Cramer ^**, Eliecer Coto , Roser Torra , Jose L. San Millan , Robert Gibson ^||||, Martijn Breuning ^¶¶, Dorien Peters ^¶¶, and David Ravine ^***

*Divisions of Nephrology and Department of Public Health Sciences, University of Toronto, and Child Health Evaluative Sciences and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, Ontario, Canada; ||Division of Nephrology, University of Modena and Reggio Emilia, Modena, Italy; ¶Division of Nephrology and **Department of Radiology, Memorial University, St. Johns, Newfoundland, Canada; Instituto de Investigaciones Nefrologicas, REDINREN, Oviedo, Division of Nephrology, Fundacio Puigvert, REDINREN, Barcelona, and Unidad de Genetica Molecular, Hospital Ramon y Cajal, Madrid, Spain; ||||Department of Radiology, University of Melbourne, Melbourne, Australia; ¶¶Leiden University Medical Center, Leiden, Netherlands; and ***School of Medicine and Pharmacology, Western Australian Institute for Medical Research, Perth, Australia

¹ To whom correspondence should be addressed. E-mail: york.pei{at}uhn.on.ca.

	Abstract

Individuals who are at risk for autosomal dominant polycystic kidney disease are often screened by ultrasound using diagnostic criteria derived from individuals with mutations in PKD1. Families with mutations in PKD2 typically have less severe disease, suggesting a potential need for different diagnostic criteria. In this study, 577 and 371 at-risk individuals from 58 PKD1 and 39 PKD2 families, respectively, were assessed by renal ultrasound and molecular genotyping. Using sensitivity data derived from genetically affected individuals and specificity data derived from genetically unaffected individuals, various diagnostic criteria were compared. In addition, data sets were created to simulate the PKD1 and PKD2 case mix expected in practice to evaluate the performance of diagnostic criteria for families of unknown genotype. The diagnostic criteria currently in use performed suboptimally for individuals with mutations in PKD2 as a result of reduced test sensitivity. In families of unknown genotype, the presence of three or more (unilateral or bilateral) renal cysts is sufficient for establishing the diagnosis in individuals aged 15 to 39 y, two or more cysts in each kidney is sufficient for individuals aged 40 to 59 y, and four or more cysts in each kidney is required for individuals 60 yr. Conversely, fewer than two renal cysts in at-risk individuals aged 40 yr is sufficient to exclude the disease. These unified diagnostic criteria will be useful for testing individuals who are at risk for autosomal dominant polycystic kidney disease in the usual clinical setting in which molecular genotyping is seldom performed.