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Low TGF-beta1 serum levels are a risk factor for atherosclerosis disease in ESRD patients
Sergio Stefoni1, Giuseppe Cianciolo, Gabriele Donati
1Nephrology Dialysis and Renal Transplantation Unit, Department of Clinical Medicine and Applied Biotechnology, S. Orsola University Hospital, Bologna, Italy. sstefoni@almans.unibo.it
Background:
It is thought that transforming growth factor-beta1 (TGF-beta1) might be a key inhibitor of atherogenesis in non-uremic patients. We evaluated the intra- and post-dialytic serum levels of TGF-beta1 in uremic patients to assess if TGF-beta1 is an independent risk factor for cardiovascular diseases, and if any correlation exists between TGF-beta1 and any yet known atherosclerotic risk factors.
Methods:
We studied 155 patients who were on regular hemodialysis, with or without clinically significant atherosclerotic vascular disease. Forty-one apparently healthy people were enrolled as a control group. TGF-beta1 was evaluated during the midweek dialysis session, at times 0, 30, and 120 minues, at the end of the session, and 3 hours after the session's end. All hitherto known atherosclerotic risk factors also were evaluated. The investigation was performed over a 24-month follow-up.
Results:
TGF-beta1 values (mean +/- SD) in dialysis patients were 26.64 +/- 7.0 ng/mL (N=155) compared with 42.31 +/- 6.0 ng/mL in the control group (N=41, P < 0.0001). A weak inverse correlation emerged between TGF-beta1 and age (r=-0.28), TGF-beta1 and lipoprotein(a) [Lp(a); r=-0.35], TGF-beta1 and C-reactive protein (CRP; r=-0.27), and TGF-beta1 and plasminogen activator inhibitor-1 (PAI-1; r=-0.41). TGF-beta1 also correlated with albumin (r=0.31). In the coronary heart disease (CHD) group (N=32) the TGF-beta1 was 26.2 +/- 4.9 ng/mL; in the cerebrovascular disease (CVD) group (N=8) it was 26.7 +/- 3.7 ng/mL and in the peripheral vascular disease (PVD) group (N=9) it was 25.4 +/- 1.7 ng/mL. In dialysis patients with no cardiovascular disease (N=80) TGF-beta1 was 35.1 +/- 6.8 ng/mL (P < 0.0001 vs. CHD, CVD and PVD patients). TGF-beta1 was significantly lower among those patients with triple coronary vessel disease than with the other CHD patients. The Cox analysis demonstrated that a 1 ng/mL reduction in TGF-beta1 concentration was associated with a 9% increase in the relative risk of a cardiovascular event.
Conclusions:
TGF-beta1 was significantly reduced in hemodialysis patients, in particular in those with severe cardiovascular disease. Baseline TGF-beta1, diabetes mellitus and serum albumin levels proved to be the only independent contributors to atherosclerotic risk in dialysis patients.