Urinary transforming growth factor-β1 in various types of nephropathy

Abstract

Transforming growth factor-β1 (TGF-β1) is a potent multifunctional polypeptide that is involved in normal renal function and in the development of glomerular sclerosis. It is also an important mediator of the immune and anti-inflammatory responses. The purpose of this study was to examine whether the measurement of urinary TGF-β1 excretion in patients with different types of renal diseases and in newly diagnosed type 1 diabetes mellitus represents a non-invasive tool to evaluate disease activity and to monitor response to therapy. We studied the urinary excretion of TGF-β1 in 57 nephropathic patients divided in different groups according to the underlying disease: 15 had mesangial glomerulonephritis (IgAGN), 9 membranous glomerulonephritis (MGN), 7 rapidly progressive glomerulonephritis (RPGN), 8 systemic lupus erythematosus (SLE), 9 interstitial nephritis (IN), 9 chronic renal failure (CRF). TGF-β1 was also measured in 38 patients with type 1 (insulin-dependent) diabetes mellitus (12 with newly diagnosed diabetes, 26 long-standing diabetes) and 31 healthy controls. Total urinary TGF-β1 concentration was assayed by enzyme-linked immunoassay (ELISA), and expressed as a ratio to urinary creatinine concentration. The urinary TGF-β1 levels were compared with the findings of biopsy and clinical parameters. Urinary TGF-β1 excretion was significantly increased in all groups except MGN, IN and CRF. In non-diabetic patients, urinary TGF-β1 levels correlated with crescent formation, floccular adhesion and mesangial proliferation, but not with the degree of tubulo-interstitial fibrosis. Urinary TGF-β1 levels did not correlate with indices of renal function (serum creatinine, glomerular filtration rate (GFR), albumin excretion rate [AER]). Among diabetic patients, HbA 1C significantly correlated with TGF-β1 urinary excretion. Urinary TGF-β1 levels may represent a valid indicator of acute glomerular flogosis associated with mesangial proliferation in glomerulonephrities. In newly diagnosed diabetic patients, hyperglycaemia seems to represent the principal factor leading to TGF-β1 overproduction. Follow-up studies of urinary TGF-β1 levels measured during optimal glycaemic control are necessary to clarify the relationship between hyperglycaemia and TGF-β1 excretion.