Unified criteria for ultrasonographic diagnosis of ADPKD

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 > or = 60 yr. Conversely, fewer than two renal cysts in at-risk individuals aged > or = 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.

Figure 1.

Comparison of renal cyst number between affected individuals with PKD1 (▪) and PKD2 ( ); diagnosed by molecular genotyping. (Top) Percentage of affected individuals who had different number of total renal cysts and were between 15 and 29 yr of age (n = 113 for PKD1 group; n = 41 for PKD2 group). (Bottom) Percentage of affected individuals with different number of total renal cysts between 30 and 59 yr of age (n = 170 for PKD1 group; n = 121 for PKD2 group). Affected individuals with PKD2 had a milder renal cyst burden compared with affected indivduals with PKD1 in both age groups (P < 0.0001 by Fisher exact test).