Nephrology Dialysis Transplantation, Vol 12, Issue 12 2562-2568, Copyright © 1997 by Oxford University Press
E Honkanen, A Teppo, T Tornroth, P Groop and C Gronhagen-Riska
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
non-proteinuric 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 indicted 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. Key words: growth factors;
immunosuppressive therapy; progression; fibrosis
ORIGINAL ARTICLES
Urinary transforming growth factor-{beta}1 in membranous glomerulonephritis
Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Kasarmikatu 11-13, FIN-00130 Helsinki, Finland; Corresponding author
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