The Diagnostic Accuracy of Ultrasound and Genetic Tests for the Diagnosis of Autosomal Dominant Polycystic Kidney Disease: A Systematic Mapping Review

OBJECTIVES: Autosomal Dominant Polycystic Kidney Disease (ADPKD, estimated prevalence 1 in 1000) causes kidney failure and is inherited by 50% of offspring. Diagnostic uncertainty due to poor ultrasound sensitivity under age 40 argues for genetic testing, now increasingly affordable, which may provide earlier diagnosis. Continued identification of new pathogenic variants and evolving genetic technologies justify systematic mapping of genetic and ultrasound diagnostic test accuracy (DTA).

METHODS: Medline, Embase and Cochrane were searched (August 2023) for studies of genetic or ultrasound tests in those clinically diagnosed or at 50% risk of inheriting ADPKD. Acceptable reference standards were definitive imaging after age 40 or genetic confirmation. Studies reporting sensitivity and specificity, or detection rates if insufficient DTA evidence, were included and mapped.

RESULTS: From 1029 non-duplicate titles retrieved, 51 genetic and 7 ultrasound studies were included. There were no studies of genetic tests in people at 50% risk. Amongst studies in patients with clinical diagnoses, genetic test methodologies were highly heterogeneous (e.g., short and long read targeted next generation (n=21), targeted sanger (n=19), whole exome sequencing (n=1)) and often enhanced by multi-ligation probe analysis (n=13). Detection rates (range 60% to 100%) did not appear to improve over time. Ultrasound sensitivity and specificity generally improved with age (lowest reported 31% and 88% respectively in polycystic kidney disease (PKD)2 patients aged 5-14; highest 100% and 100% respectively in multiple gene/age categories), and were worse in PKD2 patients compared to PKD1.

CONCLUSIONS: Despite technological advances, genetic DTA was static over time, possibly because clinical diagnostic criteria (and hence populations recruited) widened from PKD1 to include PKD2 and other phenotypes. This and data limitations cause uncertainty about genetic DTA in relatives. Relatives of patients whose pathogenic variant is genetically unidentified will need serial ultrasound scans with potentially decades of uncertainty. Unified genomic test taxonomies would facilitate future reviews.