Urine excretion of transforming growth factor-beta1 in chronic allograft nephropathy

Transforming growth factor-beta1 (TGF-beta1) a multifunctional growth cytokine, has been implicated in the pathogenesis of chronic allograft nephropathy (chgn). The primary objective of the present study was to establish whether or not concentration of TGF-beta1 in the sera and urine of transplant patients might be regarded as a chgn diagnostic factor and chgn activity indicator. Another objective was to investigate the response of this growth factor to arterial hypertension and metabolic disorder. Examined were 34 patients with chgn (Group I), 50 patients with a stable allograft function (Group II), and 25 healthy subjects (control). Follow-up since transplantation was 76 +/- 34 months in patients of Group I and 59 +/- 36 months in patients of Group II. Both groups of patients received maintenance triple immunosuppressive therapy. In all the subjects examined, determinations were carried out for serum and urine levels of TGF-beta1 by the immunoenzymatic method. Hypertension was found in all patients of Group I and in 60% of patients of Group II; low levels of HDL cholesterol below I mM were observed in 52% of Group I patients and in 22% of Group II patients. Serum concentrations of TGF-beta1 were similar in all the subjects examined. Patients with chgn showed elevated urine excretion of TGF-beta1, as compared to patients with no graft dysfunction or to the control. Urine excretion of TGF-beta1 was noticeably higher in patients with developed interstitial tissue fibrosis (I-st degree of interstitial fibrosis 6.8 +/- 4.9ng/mg cr. vs. 13.3 +/- 4.7 ng/mg cr. in III-rd degree of fibrosis). Urinary TGF-beta1 levels were correlated with arterial blood pressure, but they had a negative correlation with the HDL cholesterol level.

1) In chronic renal graft rejection urine secretion of TGF-beta1 was increased; 2) Urine secretion of TGF-beta1 was associated with arterial hypertension, degree of interstitial tissue fibrosis, and progression of graft insufficiency; 3) The negative correlation between HDL level and urine secretion of TGF-beta1 (both in patients with chronic rejection and in recipients with a stable graft function) suggests the influence of dyslipidemia on the secretion of this growth factor.