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Kidney Week

Abstract: TH-PO501

Case Report of a Novel NRIP1 Gene Mutation: Disease Association or Mere Coincidence?

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Asif, Sabaa, University of Toronto, Toronto, Ontario, Canada
  • Naimark, David M., University of Toronto, Toronto, Ontario, Canada
Introduction

Nuclear receptor-interacting protein 1 (NRIP 1) is known for its role in several physiological processes. These include and are not limited to ovulation; mammary gland development; lipid and glucose metabolism in adipose tissue, muscle and liver; regulation of inflammatory processes; maintenance of cognitive function; and cardiac function. Recently, case studies have shown an association between truncating NRIP-1 mutations and CAKUT (Congenital Anomalies of the Kidney and Urinary Tract).

Case Description

A 40-year-old woman presented in 2021, with idiopathic, non-ischemic cardiomyopathy and stage 5 chronic kidney disease (CKD) of unknown etiology. Investigations were inconclusive. Other comorbid conditions included, migraine headaches, anemia and diagnosis of mixed connective tissue disease versus fibromyalgia, with positive anti-nuclear antibodies and antinuclear ribonucleoprotein-A antibodies. In late 2023, she was admitted to a hospital with retropharyngeal abscess, and mediastinitis with progression of CKD, requiring initiation of hemodialysis. Prior to admission she had renal imaging as part of kidney transplant evaluation, which showed suspicious renal mass. Magnetic resonance imaging of the kidneys during the admission demonstrated multiple bilateral renal masses. These were confirmed to be lipid-free angiomyolipomas on biopsy. The kidney itself had changes suggestive of chronic hypoperfusion. There were no findings suggestive of any urinary tract abnormalities on imaging. Genetic testing showed a heterozygous c.1203A>C, pArg401Ser, missense mutation of the gene for NRIP1 which is novel.

Discussion

NRIP1 mutations have been associated with different malignant tumors, CAKUT and heart failure. The NRIP1 missense mutation observed in this case could be the etiology of the non-ischemic cardiomyopathy or the first documentation of its association with renal angiomyolipoma. Studies have demonstrated that NRIP1 missense mutations are also present in disease-free controls, hence, further studies are required to validate this association.

Angiomyolipoma of the right kidney.