Prognostic value of glomerular collagen IV immunofluorescence studies in male patients with X-linked Alport syndrome.
OBJECTIVE
X-linked Alport syndrome (X-AS) is caused by mutations of the COL4A5 gene, which encodes for the collagen IV α5 chain (α5[COLIV]), resulting in structural and functional abnormalities of the glomerular basement membrane (GBM) and leading to CKD. The aim of the present study was to evaluate the prognostic value of residual collagen IV chain expression in the GBM of patients with X-AS.


METHODS
The medical records of 22 patients with X-AS from 21 unrelated families collected between 1987 and 2009 were reviewed (median age at last follow-up, 19.9 years; range, 5.4-35.1 years); GBM expression of α1, α3, and α5(COLIV) chains was assessed by immunofluorescence microscopy.


RESULTS
GBM distribution of the α5(COLIV) chain was diffuse in 1 and segmental or absent in 21 of the 22 patients; the expression of the α3(COLIV) chain was diffuse in 5 of 22 patients and segmental or absent in 17 of 22 patients. Patients with diffuse staining for the α3(COLIV) chain presented with proteinuria significantly later (median age, 16.9 versus 6.1 years; P=0.02) and reached an estimated GFR < 90 ml/min per 1.73 m(2) at an older age (median age, 27.0 versus 14.9 years; P=0.01) compared with patients with segmental or absent staining. Two thirds of patients with abnormal α3(COLIV) expression by immunofluorescence studies had null or truncating COL4A5 mutations, as opposed to none of the 4 tested patients with diffuse α3(COLIV) chain glomerular distribution.


CONCLUSIONS
These results indicate that maintained expression of the α3(COLIV) chain is an early positive prognostic marker in patients with X-linked Alport symdrome.
Nephrology and Dialysis Unit, Department of Nephrology and Urology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. laura.massella@opbg.net
Laura
L
Massella
Concetta
C
Gangemi
Kostas
K
Giannakakis
Antonella
A
Crisafi
Tullio
T
Faraggiana
Chiara
C
Fallerini
Alessandra
A
Renieri
Andrea Onetti
AO
Muda
Francesco
F
Emma
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001324:Autoantigens / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000032:analysis*; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D050533:Glomerular Basement Membrane / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008856:Microscopy, Fluorescence; D009394:Nephritis, Hereditary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
D001324:Autoantigens; D015415:Biomarkers; C547475:COL4A1 protein, human; C478159:COL4A5 protein, human; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain