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. 2013 May;8(5):749-55.
doi: 10.2215/CJN.07510712. Epub 2013 Jan 31.

Prognostic value of glomerular collagen IV immunofluorescence studies in male patients with X-linked Alport syndrome

Laura Massella  1 , Concetta Gangemi, Kostas Giannakakis, Antonella Crisafi, Tullio Faraggiana, Chiara Fallerini, Alessandra Renieri, Andrea Onetti Muda, Francesco Emma
Affiliations

Prognostic value of glomerular collagen IV immunofluorescence studies in male patients with X-linked Alport syndrome

Laura Massella et al. Clin J Am Soc Nephrol. 2013 May.

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

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Figures

Figure 1.
Figure 1.
Immunohistochemistry of α5(COLIV) and α3(COLIV) in glomerular basement membrane. (A) Normal glomerular distribution of α5(COLIV) and α3(COLIV); staining with α1(COLIV) chain (Bowman capsule and tubular basal membrane) was used as internal control. (B) Examples of diffuse, segmental, and absent staining for the α3(COLIV) chain in patients with X-linked Alport syndrome.
Figure 2.
Figure 2.
Renal measures at biopsy. (A and B) Correlation between age at biopsy and estimated GFR (eGFR) (A) and between the age at biopsy and proteinuria (B). Empty circles indicate patients with diffuse α3 chain immunofluorescence pattern; filled circles indicate patients with segmental or absent α3 expression by immunofluorescence.
Figure 3.
Figure 3.
Survival curves in patients with or without diffuse α3(COLIV) chain expression. Probability of developing proteinuria (A), sensorineural deafness (B), CKD (C), and ESRD (D) according to the immunofluorescence staining of the α3(COLIV) chain in the glomerular basement membrane. CKD was defined as stage II or greater. Dashed lines indicate patients with diffuse α3 chain expression by immunofluorescence; solid lines indicate patients with segmental or absent α3 staining. Vertical bars indicate censured data. A, absent; D, diffuse; S, segmental.
See this image and copyright information in PMC

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