An Unusual Case of CKD and Kidney Cysts: It's All in the Family

Introduction: Autosomal dominant kidney disease with renal cysts and family history of progressive kidney disease suggests diagnoses such as polycystic kidney disease, tuberous sclerosis or von Hipple-Lindau syndrome. We present a rare and unusual case in which genetic testing was essential in establishing the diagnosis. Case Description: A 55 yo woman with HTN was referred for evaluation of chronic kidney disease (CKD). The kidney function had been normal (SCr of 0.7 mg/dl) but over the next few yrs the SCr increased to 1.9 mg/dl. There was no history of NSAID abuse. The urinalysis was normal and the UAC and UPC ratios were normal at 30 and 140 mg/g, respectively. Uric acid and magnesium levels were normal. Serologic evaluation (ANA, Scl 70 Ab, SSA/SSB, RF, SIEP and UIEP) was negative. CT imaging revealed bilateral renal cysts (Image). The pt's father and paternal grandfather had HTN and ESRD of unknown etiology requiring dialysis at ages 50 and 70, respectively. The pt underwent a renal biopsy which demonstrated non-diagnostic moderate tubule-interstitial fibrosis and global sclerosis and severe arterial sclerosis (Image). Genetic testing revealed a heterozygous whole gene deletion of hepatocyte nuclear factor1 β (HNF1β). Discussion: HNF1β is expressed in the kidney and regulates tubular transport and architecture. It is autosomal dominant and mutations exhibit incomplete penetrance with variable expressivity and result in progressive tubule-interstitial kidney disease and renal cysts. Mutations in HNF1β are an addition to the differential of autosomal dominant tubule-interstitial kidney disease (ADTKD) which previously included mutations in ADTKD-UMOD, -MUC1 and -REN. This case demonstrates the vital role genetic testing can play in making a diagnosis in a patient with CKD of unknown origin.CT kidneys and H&E light microscopy