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Evidence that NPHS2-R229Q predisposes to proteinuria and renal failure in familial hematuria

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Abstract

Background

Familial hematuria (FH) is associated with at least two pathological entities: thin basement membrane nephropathy (TBMN), caused by heterozygous COL4A3/COL4A4 mutations, and C3 nephropathy caused by CFHR5 mutations. It is now known that TBMN patients develop proteinuria and changes of focal segmental glomerulosclerosis when biopsied. End-stage kidney disease (ESKD) is observed in 20% of carriers, at ages 50–70. A similar progression is observed in CFHR5 nephropathy. Recent evidence suggests that NPHS2-R229Q, a podocin polymorphism, may contribute to proteinuria in TBMN and to micro-albuminuria in the general population.

Case-Diagnosis/Treatment

NPHS2-R229Q was screened in a Cypriot FH cohort. 102 TBMN patients with three known COL4 mutations and 45 CFHR5 male patients with a single mutation were categorized as “Mild” or “Severe”, based on the presence of microhematuria only, or proteinuria and chronic kidney disease. Nine R229Q carriers were found in the “Severe” category and none in the “Mild” (p=0.010 for genotypic association; p=0.043 for allelic association, adjusted for patients’ relatedness), thus supporting the possible contribution of 229Q allele in disease progress.

Conclusions

Our results offer more evidence that in patients with FH, NPHS2-R229Q predisposes to proteinuria and ESKD. R229Q may be a good prognostic marker for young hematuric patients.

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Acknowledgements

The authors express their gratitude to all patients and relatives who participated and made this study possible. The work was supported by the Cyprus Research Promotion Foundation, through grant NEW INFRASTRUCTURE/STRATEGIC/0308/24 to CD and through the University of Cyprus articles 3/311 and 3/346 (CD)

Conflict of interest

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Authors and Affiliations

  1. Department of Biological Sciences, Molecular Medicine Research Center and Laboratory of Molecular and Medical Genetics, University of Cyprus, Kallipoleos 75, 1678, Nicosia, Cyprus

    Konstantinos Voskarides & Constantinos Deltas

  2. Department of Nephrology, Limassol General Hospital, Limassol, Cyprus

    Maria Arsali

  3. Department of Nephrology, Nicosia General Hospital, Nicosia, Cyprus

    Yiannis Athanasiou

  4. Department of Pediatrics, Archbishop Makarios III Hospital, Nicosia, Cyprus

    Avraam Elia

  5. Department of Nephrology, Hippocrateon Hospital, Nicosia, Cyprus

    Alkis Pierides

Authors
  1. Konstantinos Voskarides
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  2. Maria Arsali
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  3. Yiannis Athanasiou
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  4. Avraam Elia
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  5. Alkis Pierides
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  6. Constantinos Deltas
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Corresponding author

Correspondence to Constantinos Deltas.

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Voskarides, K., Arsali, M., Athanasiou, Y. et al. Evidence that NPHS2-R229Q predisposes to proteinuria and renal failure in familial hematuria. Pediatr Nephrol 27, 675–679 (2012). https://doi.org/10.1007/s00467-011-2084-6

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  • DOI: https://doi.org/10.1007/s00467-011-2084-6

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