Lipid‐lowering treatment and inflammatory mediators in diabetes and chronic kidney disease

Abstract

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. 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) 15-59mL/min×1·73m(2) (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR >75mL/min (DM only) were included. 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. 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.