Urinary transforming growth factor-beta 1 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 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 60-16,970) 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 (1610-16,960) 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.
Honkanen
E
E
Department of Medicine, Helsinki University Central Hospital, Finland.
Teppo
A M
AM
Törnroth
T
T
Groop
P H
PH
Grönhagen-Riska
C
C
D000328:Adult; D000368:Aged; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy / Q000473:pathology / Q000652:urine*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000150:complications; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000652:urine*
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta