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Autosomal Dominant Tubulointerstitial Kidney Disease—Uromodulin Misclassified as Focal Segmental Glomerulosclerosis or Hereditary Glomerular Disease

Justin Chun, Minxian Wang, Maris S. Wilkins, Andrea U. Knob, Ava Benjamin, Lihong Bu, Martin R. Pollak

2020Kidney International Reports26 citationsDOIOpen Access PDF

Abstract

INTRODUCTION: , a gene encoding the tubular protein uromodulin, in 8 families with suspected glomerular disease. METHODS: was performed by Sanger sequencing. RESULTS: co-segregating with disease. Consistent with ADTKD, most patients in our study presented with autosomal dominant inheritance, subnephrotic range proteinuria, minimal hematuria, and renal impairment. Kidney biopsies showed histologic features of glomerular injury consistent with secondary FSGS, including focal sclerosis and partial podocyte foot process effacement. CONCLUSION: Our study demonstrates that with the use of standard clinical testing and kidney biopsy, clinicians were unable to make the diagnosis of ADTKD-UMOD; patients were often labeled with a clinical diagnosis of FSGS. We show that genetic testing can establish the diagnosis of ADTKD-UMOD with secondary FSGS. Genetic testing in individuals with FSGS histology should not be limited to genes that directly impair podocyte function.

Topics & Concepts

Tamm–Horsfall proteinFocal segmental glomerulosclerosisMedicinePathologyKidney diseaseDiseaseKidneyGlomerulonephritisInternal medicineRenal Diseases and GlomerulopathiesChronic Kidney Disease and DiabetesGenetic and Kidney Cyst Diseases