Autosomal Recessive PKD with Congenital Hepatic Fibrosis in Adults: Diagnostic Challenges and Phenotypic Overlap with ADPKD, a Single-Center Experience

Background: Autosomal Recessive Polycystic Kidney Disease–Congenital Hepatic Fibrosis (ARPKD-CHF) is a rare autosomal recessive ciliopathy, classically presenting in infancy with enlarged echogenic kidneys, pulmonary hypoplasia, and high perinatal mortality. The ARPKD-CHF phenotype includes renal and hepatobiliary involvement. While many children progress to ESRD early, later-onset forms remain under-characterized. Adult presentations often mimic ADPKD, complicating diagnosis. Methods: Building upon our prior analysis presented in 2021, we expanded our cohort and retrospectively reviewed patients >16 yrs with cystic kidney disease and/or CHF. Diagnosis was based on characteristic hepato-renal features and/or biallelic PKHD1 variants. Demographics, imaging, renal function, and genetic data were extracted. Results: Of 44 pts with ARPKD-CHF, 28 were adults (mean age 34, median 29; 32% male; 11% Hispanic). All had hepatobiliary involvement: 36% had CHF, 54% portal HTN, 61% splenomegaly, 29% liver cysts. One required liver transplant in infancy. Renal imaging showed cysts in 93%, large echogenic kidneys in 18%, poor cortico-medullary (C-M) differentiation in 8%, MSK in 15%, and salt-and-pepper pattern in 11%. Among 11 pts (39%) with biallelic PKHD1 variants, 5 had KT before age 20. Overall, 25% reached ESRD or KT; 2 required KT after age 45. Non-ESRD pts (n=21) had mean eGFR 46 mL/min/1.73m2; 50% had eGFR ≥60. Some had minimal renal abnormalities despite significant hepatic disease. Conclusion: This adult ARPKD cohort demonstrates a milder renal course than the classical pediatric phenotype, with delayed or absent progression to ESRD. Hepatic findings were universal, often preceding renal signs. Several pts had imaging features (e.g., multiple renal cysts) resembling ADPKD, complicating diagnosis. These findings highlight the underrecognition of ARPKD-CHF in adults and underscore the need for heightened suspicion and genetic testing in adults with unexplained hepatorenal disease. Broader diagnostic criteria may help prevent misclassification and inform management.