Lipid-lowering treatment and inflammatory mediators in diabetes and chronic kidney disease.

Abstract

BACKGROUND:

Inflammation may contribute to the high cardiovascular risk in diabetes mellitus (DM) and chronic kidney disease (CKD). Monocyte chemoattractant protein-1 (MCP-1) facilitates the recruitment of monocytes into atherosclerotic lesions and is involved in diabetic nephropathy. Interferon gamma (IFNγ) is important in atherosclerosis and increases the synthesis of chemokines including MCP-1. Lipid-lowering treatment (LLT) with statins may have anti-inflammatory effects, and ezetimibe cotreatment provides additional cholesterol lowering.

METHODS:

After a placebo run-in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S+E) were compared in a randomized, double-blind, cross-over study on inflammatory parameters. Eighteen DM patients with estimated glomerular filtration rate (eGFR) 15-59 mL/min × 1·73 m(2) (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR > 75 mL/min (DM only) were included.

RESULTS:

At baseline, monocyte chemoattractant protein 1 (MCP-1) (P = 0·03), IFNγ (P = 0·02), tumour necrosis factor-α (TNFα) (P < 0·01) and soluble vascular adhesion molecule (sVCAM) (P = 0·001) levels were elevated in DM-CKD compared with DM-only patients. LLT with S and S+E reduced MCP-1 levels (P < 0·01 by anova) and IFNγ levels (P < 0·01) in DM-CKD patients but not in DM-only patients. Reductions were most pronounced with the combination treatment.

CONCLUSIONS:

DM patients with CKD stages 3-4 had increased inflammatory activity compared with DM patients with normal GFR. Lipid-lowering treatment decreased the levels of MCP-1 and IFNγ in DM patients with concomitant CKD, which may be beneficial with regard to the progression of both atherosclerosis and diabetic nephropathy.

• Authors: Tora Almquist, Stefan H Jacobson, Fariborz Mobarrez, Per Näsman, Paul Hjemdahl
• Journal: European journal of clinical investigation (Eur J Clin Invest) Vol. 44 Issue 3 Pg. 276-84 ( 2014) ISSN: 1365-2362 [Electronic] England
• PMID: 24720535 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

Chemical References

• Anticholesteremic Agents
• Azetidines
• CCL2 protein, human
• Chemokine CCL2
• Inflammation Mediators
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Interferon-gamma
• Simvastatin
• Ezetimibe

Topics

• Aged
• Anticholesteremic Agents (therapeutic use)
• Azetidines (therapeutic use)
• Case-Control Studies
• Chemokine CCL2 (immunology)
• Cross-Over Studies
• Diabetes Mellitus (drug therapy, immunology)
• Diabetic Nephropathies (drug therapy, immunology)
• Double-Blind Method
• Drug Therapy, Combination
• Ezetimibe
• Female
• Humans
• Inflammation (immunology)
• Inflammation Mediators (immunology)
• Interferon-gamma (immunology)
• Male
• Middle Aged
• Renal Insufficiency, Chronic (drug therapy, immunology)
• Simvastatin (therapeutic use)
• Tumor Necrosis Factor-alpha (immunology)
• Vascular Cell Adhesion Molecule-1 (immunology)