Lipid-lowering treatment and inflammatory mediators in diabetes and chronic kidney disease.
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.
Department of Medicine Solna, Clinical Pharmacology Unit, Karolinska Institutet, Karolinska University Hospital/Solna, Stockholm, Sweden; Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
Tora
T
Almquist
Stefan H
SH
Jacobson
Fariborz
F
Mobarrez
Per
P
Näsman
Paul
P
Hjemdahl
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000276:immunology; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000276:immunology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000276:immunology; D019821:Simvastatin / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D000924:Anticholesteremic Agents; D001384:Azetidines; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D007371:Interferon-gamma; D019821:Simvastatin; D000069438:Ezetimibe
Chronic kidney disease; diabetes mellitus; inflammation; lipid-lowering treatment