Unmasking Late-Onset Autosomal Recessive PKD

Introduction: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy caused by biallelic pathogenic mutations in the PKHD1 gene. Late-onset ARPKD can present with atypical features and a variable phenotype, making diagnosis challenging. Case Description: 30 yo female presented for evaluation of ESRD of unknown origin. She had been on dialysis for 3 months; had no extrarenal manifestations and had no family history of kidney disease. Lab testing revealed: creatinine 6.5 mg/dL, eGFR 8 mL/min, UACR 900 mg/g, UPCR 3500 mg/g and urine microscopy >25 RBC/HPF. LFTs, platelets and INR level were normal. A glomerular disease panel did not show abnormalities. An abdominal CT revealed normal-sized kidneys with diffuse cystic involvement. Renal biopsy showed advanced global glomerulosclerosis and advanced interstitial fibrosis & tubular atrophy. Features of active inflammation were absent. There were no immune complex deposits. A kidney gene panel identified biallelic pathogenic mutations in the PKHD1 gene, confirming a diagnosis of ARPKD. Notably, the patient exhibited no classic hepatobiliary features, often seen in ARPKD. Discussion: In this case, the absence of hepatobiliary features, normal kidney size and negative family history, initially obscured the diagnosis. The differential diagnosis included other cystic kidney diseases, glomerulonephritis or Alport syndrome. The detection of biallelic PKHD1 pathogenic mutations yielded a diagnosis of ARPKD putting an end to a diagnostic conundrum and underscoring the need to screen family members at risk of being carriers. The efficacy of tolvaptan to mitigate kidney disease progression in ARPKD is currently being evaluated. ARPKD is often diagnosed in childhood. Patients present with large cystic kidneys and progressive CKD. Liver fibrosis, accompanied by dilated bile ducts (Caroli syndrome), often occurs later in life, resulting in portal hypertension and ascending cholangitis. Dual liver-kidney transplantation can be considered in selected patients, as ARPKD is not known to recur post-transplantation. Late-onset ARPKD usually presents with mild kidney disease and hepatobiliary disease often becomes more prominent. Rarely, ARPKD can present with symptoms confined to a single organ. Conclusion Late-onset ARPKD can present with a kidney-restricted disease phenotype and it should be considered in young adults with multiple kidney cysts and unexplained ESRD.