Nephrol Dial Transplant (2002) 17: 2145-2152
© 2002 European Renal Association-European Dialysis and Transplant Association
Transforming growth factor-ß1 in the kidney and urine of patients with glomerular disease and proteinuria
1 Department of Internal Medicine—Nephrology, University Hospital, Patras, Greece and 2 Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK
Background. Transforming growth factor-ß1 (TGF-ß1) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-ß1 in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-ß1.
Methods. Twenty-five patients with heavy proteinuria (8.4±3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-ß1 mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-ß1 levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion.
Results. The site of synthesis and expression of TGF-ß1 in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-ß1 expression was found only in patients with mesangial proliferation. Urinary TGF-ß1 excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783±280 vs 310±140 and 375±90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-ß1 excretion was significantly reduced (from 749±290 to 495±130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated.
Conclusions. The localization of TGF-ß1 mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-ß1 production.
Keywords: glomerular injury; proteinuria; transforming growth factor-ß1
Correspondence and offprint requests to: Dr D. Goumenos, Department of Internal Medicine—Nephrology, University Hospital of Patras, Patras 26500, Greece. Email: dgoumenos{at}med.upatras.gr
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