Lipid-lowering treatment and inflammatory mediators in diabetes and chronic kidney disease
2014 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 44, no 3, 276-284 p.Article in journal (Refereed) Published
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 m2 (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.
Place, publisher, year, edition, pages
2014. Vol. 44, no 3, 276-284 p.
Chronic kidney disease, Diabetes mellitus, Inflammation, Lipid-lowering treatment
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:kth:diva-142342DOI: 10.1111/eci.12230ISI: 000330985500006ScopusID: 2-s2.0-84893736247OAI: oai:DiVA.org:kth-142342DiVA: diva2:699699
FunderSwedish Research Council
QC 201402282014-02-282014-02-282014-04-07Bibliographically approved