Biallelic cubilin pathogenic variants as a cause of « benign » proteinuria: implications for clinical management

Abstract

The recent description of a cohort with both adults and children harboring biallelic pathogenic variants of cubilin (CUBN) changed the paradigm for the management of isolated proteinuria. Indeed, the detection of proteinuria in a patient, regardless of age, often leads to an exhaustive check-up, including a kidney biopsy, but also to the prescription of renin-angiotensin system (RAS) blockers to slow the progression of kidney disease. Patients with CUBN variants have nondetrimental proteinuria and are non-responsive to RAS blockers. We herein describe two siblings treated for isolated proteinuria for several years, who were eventually diagnosed with CUBN biallelic pathogenic variants (c.703 C > T and c.10363-3A > G). We review the pathophysiological mechanisms of this newly discovered disease and discuss its implications for clinical management.

Keywords

Proteinuria / genetic kidney disease / cubilin / isolated albuminuria

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