De Muro, Pierina and Faedda, Rossana and Fresu, Pietro and Masala, Antonio Giovanni Emilio and Cigni, Alessandro and Concas, Gordiano and Mela, Maria Graziella and Satta, Andrea Ercole and Carcassi, Aldo and Sanna, Giovanni Maria and Cherchi, Gian Mario (2004) Urinary transforming growth factor-β1 in various types of nephropathy. Pharmacological Research, Vol. 49 (3), p. 293-298. ISSN 1043-6618. Article.
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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, HbA1C 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.
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