Urinary transforming growth factor-β1 in membranous glomerulonephritis

Background. Human idiopathic membranous glomerulonephritis (MGN) has a highly variable clinical course and factors determining its outcome are poorly known. Since transforming growth factor-beta 1 (TGF-beta 1) has an essential role in renal fibrogenesis, we studied the possibility to use urinary excretion of TGF-beta 1 in the assessment of progression of the disease in patients with MGN. Methods. Urinary TGF-beta 1 was determined in 41 patients with MGN, 25 healthy subjects, six nonproteinuric renal transplant patients, 10 patients with IgA glomerulonephritis, and seven proteinuric patients (with non-progressive diseases) using a novel, double antibody enzyme immunoassay. The results were compared with renal morphology and clinical indices of activity of MGN over 12 months. Results. The median urinary TGF-beta 1 excretion (pg/mg creatinine) was significantly higher (1730; range 60-16970) in MGN patients than in the healthy controls (300; 30-1330; P<0.0001). In renal allograft recipients the excretion was 840 (250-3440; P<0.0001 vs healthy controls), in IgA GN it was 1130 (30-4910; P=0.039), and in proteinuric patients it was 39 (29-165; P=NS). In MGN but not in the proteinuric controls or renal allograft recipients, urinary TGF-beta 1 correlated with urinary albumin excretion (r=0.86, P<0.0001) but no correlation with renal function or the duration of the disease was found. Urinary TGF-beta 1 at renal biopsy correlated with interstitial cellular inflammation and its excretion 1 year before the biopsy correlated with indices of sclerosis/fibrosis. Immunosuppressive therapy significantly decreased urinary TGF-beta 1 from 2800 (1610-16960) to 840 (170-1600) pg/mg creatinine (P=0.028). Patients with persistent nephrotic syndrome and/or declining renal function had a higher initial TGF-beta 1 excretion (median 3680; 1830-7420 pg/mg creatinine) than those entering partial or complete remission (1060; 60-1960; P= 0.003) within 12 months from sampling. Conclusions. Urinary TGF-beta 1 excretion was increased in patients with MGN, and high excretion indicated intrarenal sclerosing/fibrosing processes and progressive clinical course. Measuring urinary TGF-beta 1 may be useful in the assessment of the progression of disease and the effects of treatment in MGN.