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Ren Fail. 2008;30(2):239-46. doi: 10.1080/08860220701804979.

Fibrotic mechanisms in idiopathic rapidly progressive glomerulonephritis: the role of TGF-beta1 and C5b-9.

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1
Department of Nephrology, 'G.Papanikolaou' General Hospital, Thessaloniki, Greece.

Abstract

BACKGROUND:

Idiopathic IRPGN is a form of renal vasculitis in which a high chronicity index is present despite minimal impairment of renal function. The present study investigated the mechanisms underlining the relatively early appearance of fibrosis.

METHODS:

In all, 34 patients (17 males) with biopsy proven idiopathic RPGN were included. On light microscopy, the percentage and evolution stage of crescents, the presence of glomerular necrosis, the degree or severity of arteriosclerosis, as well as the extent of tubulointerstitial (TIN) infiltration, interstial fibrosis, and tubular atrophy were assessed. Monoclonal antibodies were used to identify infiltrating macrophages, HLA-DR (+), alpha-SMA (+), and PCNA (+) cells, the expression of the adhesion molecule ICAM-1, the growth factor TGF-beta1, and the terminal complement component C5b-9.

RESULTS:

The presence of glomerular necrosis correlated positively with the number of SMA (+) cells in TIN (p = 0.036). Glomerular TGF-beta1 expression had positive correlation with tubular C5b-9 expression. The tubulointerstitial TGF-beta1 expression correlated with tubular C5b-9 expression (p = 0.001) and TGF-beta1 expression (p = 0.009). Independent factors predicting the severity of renal function impairment were the CRP levels (p = 0.002) and the degree of arteriosclerosis (p = 0.01). CRP levels correlated with the severity of interstitial infiltration and fibrosis (p = 0.02), the expression of TGF-beta1 in the glomeruli (p = 0.009) and the interstitial space (p = 0.001), and the intensity of tubular ICAM-1 and C5b-9 expression (p = 0.023, p = 0.002, respectively). The severity of proteinuria showed a significant correlation with the expression of TGF-beta1 in the glomeruli (p = 0.033) and the tubulointerstitium (p = 0.019).

CONCLUSIONS:

The activation of interstitial fibroblasts seems to be an early phenomenon that is related to the extent of glomerular necrosis. Glomerular TGF-beta1 may induce tubular expression of C5b-9. Increased tubular C5b-9 expression may result in interstitial fibrosis through increased TGF-beta1 production.

PMID:
18300128
DOI:
10.1080/08860220701804979
[Indexed for MEDLINE]

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