CFHR5 Nephropathy Case Report: A Novel Variant Characterized by Tubulointerstitial Kidney Disease

Area of Science:

• Nephrology
• Genetics
• Rare diseases

Background:

• CFHR5 nephropathy, a C3 glomerulopathy subtype, typically presents with hematuria and proteinuria, progressing to end-stage kidney disease (ESKD), especially in males.
• It is linked to a specific CFHR5 gene duplication and follows an autosomal dominant inheritance.

Observation:

• This study identifies a novel clinical phenotype in subjects with a CFHR5 gene variant.
• Affected individuals exhibit autosomal dominant tubulo-interstitial kidney disease (ADTKD) with chronic kidney disease (CKD) of unknown origin, notably lacking hematuria and proteinuria.
• Pathology reveals tubular atrophy, interstitial fibrosis, and arterial intimal thickening, with no glomerular or filtration barrier abnormalities.

Findings:

• The novel CFHR5 variant presents as ADTKD, distinct from classic CFHR5 nephropathy.
• Males show a more severe prognosis, progressing rapidly to ESKD in their second to third decade.
• Kidney biopsies indicate significant tubulo-interstitial damage and arterial changes, but not glomerular disease.

Implications:

• This expands the known clinical spectrum of CFHR5-associated kidney diseases.
• It highlights the importance of genetic testing for CFHR5 variants in unexplained CKD, even without typical nephropathy signs.
• Further research is needed to elucidate the pathogenic mechanisms of this novel phenotype.