Low TGF-beta1 serum levels are a risk factor for atherosclerosis disease in ESRD patients.
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.
Stefoni
Sergio
S
Nephrology Dialysis and Renal Transplantation Unit, Department of Clinical Medicine and Applied Biotechnology, S. Orsola University Hospital, Bologna, Italy. sstefoni@almans.unibo.it
Cianciolo
Giuseppe
G
Donati
Gabriele
G
Dormi
Ada
A
Silvestri
Maria Grazia
MG
Colì
Luigi
L
De Pascalis
Antonio
A
Iannelli
Sandra
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000097:blood* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000401:mortality; D011237:Predictive Value of Tests; D006435:Renal Dialysis; D012307:Risk Factors; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014511:Uremia / Q000097:blood / Q000401:mortality / Q000628:therapy
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1