Thin glomerular basement membrane disease: clinical significance of a morphological diagnosis--a collaborative study of the Italian Renal Immunopathology Group.
BACKGROUND
Thin glomerular basement membrane disease (TBMD) is a nephropathy defined by diffuse thinning of the glomerular basement membrane (GBM) at electron microscopy examination, without the alterations of Alport's syndrome (ATS). It is known that many patients with TBMD have a type IV collagen disorder and that the disease occasionally may be progressive. This study investigated 51 patients with the morphological diagnosis of TBMD lacking any sign of ATS, with the aim of defining the prevalence of type IV collagen mutations and the course of the disease.


METHODS
Patients were investigated as follows: (a) clinical picture and family investigation; (b) renal biopsy findings; (c) immunohistochemical study of renal tissue for collagen IV alpha-chains; (d) pedigree reconstruction and molecular investigations in genes encoding type IV collagen chains, when DNA samples were available; and (e) follow-up data.


RESULTS
Renal biopsy analysis revealed no light microscopy changes in 27 patients and minimal abnormalities in the remainder. Global glomerular sclerosis was found in seven cases and superimposed mesangial immunoglobulin-A deposits in four. Normal staining of GBM for alpha(IV) chains was observed in all but one patient, where alpha5(IV) was absent and molecular investigation revealed a COL4A5 mutation. Five out of 25 cases had a mutation in the COL4A3/COL4A4 genes. Eight out of 38 patients followed up for 12-240 months (21%) showed signs of disease progression or hypertension.


CONCLUSIONS
This study confirms that a considerable proportion of patients with TBMD have a type IV collagen disorder and that this lesion is not always benign. Thus, families should be investigated carefully whenever possible and patients and affected relatives should be examined periodically for signs of disease progression.
Frascà
Giovanni M
GM
Nephrology, Dialysis and Renal Transplantation Unit, St Orsola University Hospital, V. Massarenti 9, 40137 Bologna, Italy. frasca@orsola-malpighi.med.unibo.it
Onetti-Muda
Andrea
A
Mari
Francesca
F
Longo
Ilaria
I
Scala
Elisa
E
Pescucci
Chiara
C
Roccatello
Dario
D
Alpa
Mirella
M
Coppo
Rosanna
R
Li Volti
Giovanni
G
Feriozzi
Sandro
S
Bergesio
Franco
F
Schena
Francesco P
FP
Renieri
Alessandra
A
D000293:Adolescent; D000328:Adult; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D001485:Basement Membrane / Q000648:ultrastructure; D002648:Child; D015331:Cohort Studies; D024141:Collagen Type IV / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006417:Hematuria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007558:Italy; D007678:Kidney Glomerulus / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009394:Nephritis, Hereditary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010375:Pedigree
D001324:Autoantigens; C466620:COL4A4 protein, human; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain