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 Ն60 yr. Conversely, fewer than two renal cysts in at-risk individuals aged Ն40 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.

Whole-genome sequencing overcomes pseudogene homology to diagnose autosomal dominant polycystic kidney disease

“…A clinical diagnosis can be difficult to make in young patients, those without a family history and those with relatively fewer cysts on imaging studies. 17 A more cost-effective and accurate molecular diagnostic test, which this technique has the potential to offer, would provide diagnostic certainty for this cohort of patients, thus avoiding serial imaging and periods of diagnostic uncertainty. A genetic diagnosis also adds clarity in the setting of living-related kidney donation, ensuring a phenotypically normal donor does not carry a pathogenic familial variant.…”

“…Patients, over the age of 18, with a diagnosis of ADPKD made based on standard clinical and imaging criteria 17 were prospectively recruited into the study. For those without a family history of ADPKD, a presumptive diagnosis of ADPKD was made if multiple bilateral renal cysts were seen on ultrasound images and there were no manifestations suggestive of another cystic kidney disease.…”

Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease

“…Kidney disease severity, including ESRD and survival status, was also collected from all available affected family members. The diagnosis of ADPKD in the study subjects was confirmed by ultrasound-based criteria 28 and/or mutation screening. For patients without a positive family history, the diagnosis of ADPKD required the presence of $10 cysts in each kidney, with both kidneys .15 cm in length.…”

Renal Relevant Radiology

“…Ultrasound is sufficient to make the diagnosis, and although the measurement of length is imprecise, it suffices for prognosis (26). Criteria for the diagnosis of ADPKD in subjects at risk have been developed based on the prevalence of sporadic cysts (27). Acquired cystic disease is associated with advanced CKD and easily distinguished from ADPKD on the basis of kidney size.…”