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Abstract: SA-PO761

HNF1B Nephropathy Mimicking Autosomal Dominant Polycystic Kidney Disease: A Case Report

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Alamri, Nada, Departments of Medicine and Health Research Methodology, McMaster University, Hamilton, Ontario, Canada
  • Lanktree, Matthew B., Departments of Medicine and Health Research Methodology, McMaster University, Hamilton, Ontario, Canada
Introduction

Hepatocyte nuclear factor1beta (HNF1B) nephropathy is characterized by hypomagnesemia, hyperuricemia, congenital anomalies of the kidneys and urinary tract (CAKUT), and multiple small cortical cysts without kidney enlargement. It also involves multi-organ manifestations including insulin-deficient diabetes (or maturity-onset diabetes of the young [MODY]), pancreatic exocrine dysfunction, liver dysfunction and neurodevelopmental abnormalities including autism spectrum disorder (ASD). We present a rare case of HNF1B nephropathy with atypical large kidney cysts mimicking autosomal dominant polycystic kidney disease (ADPKD).

Case Description

A 37-year-old male with ASD initially presented with hypertensive emergency. The patient reported occasional flank pain and distension but no other symptoms. The patient was estranged from his father, and his mother had normal kidney function without cysts. There was no known history of kidney failure, aneurysms, or sudden death in his extended family. Physical examination revealed distended abdomen with palpable organomegaly. Laboratory results showed elevated creatinine levels (2.41 mg/dl) and reduced eGFR (33 ml/min/1.73 m2) with an eGFR decline of 5 ml/min/1.73 m2 in the last year. Fasting blood glucose levels and liver function tests were normal. CT showed innumerable bilateral kidney cysts, the largest of which measured 19 cm on the right and 12 cm on the left, and an enlarged spleen. An initial diagnosis of de novo ADPKD was suspected. Genetic testing of PKD1 and PKD2 found no responsible variant, leading to a broader cystic gene panel sequencing. A heterozygous 1.26 Mb deletion (chr17:g.34842466_36104935del), encompassing whole HNF1B gene was detected. Cascade screening showed that the patient’s mother was unaffected.

Discussion

HNF1B nephropathy displays substantial phenotypic heterogeneity. We present a case of HNF1B nephropathy clinically mimicking ADPKD with extreme kidney enlargement and loss of kidney function, without hypomagnesemia, hyperuricemia, or MODY. Phenocopies are not uncommon, and this case further exemplifies the role of genetic testing to obtain a concrete diagnosis. This case report contributes to the understanding of phenotypic variability in HNF1B nephropathy and emphasizes the importance of considering this diagnosis in patients with large kidney cysts.