Journal Article

The effects of gemfibrozil upon the hypercoagulable state in dyslipidaemic patients with chronic renal failure

A. B. Irish and C. H. Thompson

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 11, issue 11, pages 2223-2228
Published in print November 1996 | ISSN: 0931-0509
e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/oxfordjournals.ndt.a027140
The effects of gemfibrozil upon the hypercoagulable state in dyslipidaemic patients with chronic renal failure

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Background.

The dyslipidaemia of chronic renal disease could contribute to a hypercoagulable state by activation of blood coagulation and/or impairment of fibrinolysis, thereby increasing cardiovascular disease (CVD) risk.

Methods.

We measured the coagulation activation marker prothrombin fragment F1 + 2 (F1 + 2), fibrinogen, plasminogen activator inhibitor- 1 activity (PAI1), interleukin-6(IL6), insulin, lipids and lipoprotein(a) (Lp(a)), in 12 patients with chronic renal disease before and after gemfibrozil.

Results.

Gemfibrozil significantly reduced triglycerides by 44% and increased HDL-cholesterol by 31% without significant change in LDL cholesterol. Before treatment, patients had increased F1 +2, fibrinogen and IL6, but similar PAI1 compared with the controls, consistent with a hypercoagulable and persistent inflammatory state. Following treatment, F 1 + 2 decreased to within the normal range and this reduction correlated with the decrease in triglycerides and inversely with the increase in HDL-cholesterol. A nonsignificant decrease in fibrinogen was inversely correl ated with a significant increase in albumin. However, Lp(a) and PAI1 activity significantly increased whilst insulin and IL6 were unchanged.

Conclusions.

Gemfibrozil improved the uraemic dyslipidaemia and hypercoagulable state by reduction in activation of blood coagulation, indirectly suggesting a reduction in lipid-dependent extrinsic pathway activity which should contribute to reduced risk of throm bosis and CVD. Reduced fibrinogen and increased albumin are consistent with a reduction in the acute phase response. Increased PAI1 and Lp(a) could impair fibrinolysis and potentially increase CVD risk, although the mechanism for these effects is uncertain but does not appear related to cytokine or insulin mediated mechanisms and requires further study. Large prospective studies are required to determine if gemfibrozil can reduce CVD events in uraemia.

Keywords: chronic renal failure; fibrinogen; gemfibrozil; insulin; interleukin-6; lipids; lipoprotein(a); prothrombin fragment F1 + 2

Journal Article.  0 words. 

Subjects: Nephrology

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