Abstract
BackgroundCrescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-β1 is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-β1 levels in patients with crescentic nephritis could be used as a marker of response to treatment.MethodsFifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-β1 was estimated in biopsy sections by immunohistochemistry and urinary TGF-β1 levels were determined by quantitative sandwich enzyme immunoassay (EIA). TGF-β1 levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange). Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls.ResultsImprovement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 ± 1.5 to 1.4 ± 0.1 mg/dl and from 4.4 ± 1.2 to 4.1 ± 0.6 mg/dl, respectively). In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-β1 levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 ± 126 ng/24 h vs. 376 ± 84 ng/24 h, p < 0.01). TGF-β1 was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-β1 immunostaining with the presence of fibrocellular cresents was observed (r = 0.531, p < 0,05).ConclusionIncreased TGF-β1 renal expression and urinary excretion that is related to the response to immunosuppressive therapy was observed in patients with crescentic nephritis. Evaluation of urinary TGF-β1 levels may be proved a useful marker of clinical outcome in patients with crescentic nephritis.
Highlights
Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced
Ney was estimated by immunohistochemistry in biopsy sections obtained from all patients whereas TGF-β1 urinary levels were measured at the time of biopsy and before the administration of immunosuppressive therapy in 12 patients and compared to those observed in 12 patients with other types of proliferative GN (IgA nephropathy n = 7, mesangiocapillary GN n = 2 and endocapillary proliferative GN n = 3) and in 10 healthy subjects
In 5 patients (33%) with antineutrophilic cytoplasmic antibodies (ANCA)(+) vasculitis who were presented with signs of uremia no improvement of renal function was observed, even with the addition of plasma exchange in the treatment protocol
Summary
Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. Crescentic nephritis is a type of glomerular disease characterized by crescent formation followed by a rapidly progressive course [1]. It can occur in cases with antibodies against glomerular basement membrane (anti-GBM disease), secondary to other glomerulonephritis and in patients with vasculitis and presence of antineutrophilic cytoplasmic antibodies (ANCA) [1]. Proliferation of parietal cells of Bowman's capsule and macrophages stimulated by cytokines and growth factors is implicated in the development of cellular crescents that soon become fibrotic and result in irreversible damage [2]. The implication of TGF-β1is further supported by the observation of amelioration of histologic damage in experimentally induced anti-GBM nephritis with the blockade of TGF-β1 action [7]
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