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CFHR5 Nephropathy Case Report: A Novel Variant Characterized by Tubulointerstitial Kidney Disease
Rita Santarsiere1, Giulia Florio2, Annalisa Gonnella3
1Department of Medical Translational Sciences, University of Campania "L. Vanvitelli", Naples, Italy.
Insights
A novel CFHR5 gene variant causes autosomal dominant tubulo-interstitial kidney disease, presenting differently from typical CFHR5 nephropathy. This variant leads to kidney failure, particularly in males, without hematuria or proteinuria.
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.
Introduction:
CFHR5 nephropathy is considered a subtype of C3 glomerulopathy. It was originally described in Greek Cypriot families and it is characterized by the time with the development of microscopic hematuria and proteinuria associated with a fast progression toward ESKD, especially in men. These symptoms present an autosomal dominant inheritance pattern and are associated with the exon 2 to 3 duplication of the CFHR5 gene.
Case Presentation:
Here, we describe a novel clinical phenotype associated with a variant of the CFHR5. The affected subjects present the clinical features of autosomal dominant tubulo-interstitial kidney disease. They present with CKD of unknown origin with no hematuria nor proteinuria. Like the classical CFHR5 nephropathy, males have a worse prognosis than females, with a fast progression toward ESKD in the second-third decade of life. Kidney pathology shows severe tubular atrophy and interstitial fibrosis and infiltrate. Arteries involvement is characterized by thickening of the intima layer, while no major alterations are described at the glomerular level. Electron microscopy confirms no interstitial or glomerular filtration barrier alterations.
Conclusion:
The exact mechanism behind this phenomenon remains unclear; we hope that our case will encourage further investigation.
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