TY - JOUR
T1 - Evidence that NPHS2-R229Q predisposes to proteinuria and renal failure in familial hematuria
AU - Voskarides, Konstantinos
AU - Arsali, Maria
AU - Athanasiou, Yiannis
AU - Elia, Avraam
AU - Pierides, Alkis
AU - Deltas, Constantinos
N1 - Funding Information:
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)
PY - 2012/4
Y1 - 2012/4
N2 - 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" (p00.010 for genotypic association; p00.043 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
AB - 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" (p00.010 for genotypic association; p00.043 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
KW - CFHR5
KW - COL4A3/COL4A4
KW - Collagen IV
KW - FSGS
KW - Modifier gene(s)
KW - Podocin
KW - Slit diaphragm
KW - TBMN
UR - http://www.scopus.com/inward/record.url?scp=84862284401&partnerID=8YFLogxK
U2 - 10.1007/s00467-011-2084-6
DO - 10.1007/s00467-011-2084-6
M3 - Article
C2 - 22228437
AN - SCOPUS:84862284401
SN - 0931-041X
VL - 27
SP - 675
EP - 679
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 4
ER -