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.
Eur J Clin Invest. 2014;44(3):276-84. doi: 10.1111/eci.12230. Epub 2014 Jan 22.
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) 15-59 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.
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.
炎症可能导致糖尿病（DM）和慢性肾脏病（CKD）患者心血管疾病风险升高。单核细胞趋化蛋白-1（MCP-1）促进单核细胞向动脉粥样硬化病变募集，并参与糖尿病肾病。干扰素γ（IFNγ）在动脉粥样硬化中起重要作用，并增加趋化因子包括 MCP-1 的合成。他汀类药物的降脂治疗（LLT）可能具有抗炎作用，而依折麦布联合治疗则提供额外的降胆固醇作用。
在安慰剂导入期后，我们进行了一项随机、双盲、交叉研究，比较了单独使用辛伐他汀（S）或辛伐他汀+依折麦布（S+E）对炎症参数的影响。纳入了 18 例 DM 患者（肾小球滤过率[eGFR]为 15-59 mL/min×1·73 m(2)，CKD 分期 3-4 期[DM-CKD]）和 21 例 DM 患者（eGFR >75 mL/min，DM 患者）。
基线时，与仅 DM 患者相比，DM-CKD 患者的单核细胞趋化蛋白 1（MCP-1）（P=0·03）、IFNγ（P=0·02）、肿瘤坏死因子-α（TNFα）（P<0·01）和可溶性血管细胞黏附分子（sVCAM）（P=0·001）水平升高。辛伐他汀和 S+E 的 LLT 降低了 DM-CKD 患者的 MCP-1 水平（anova 比较 P<0·01）和 IFNγ 水平（P<0·01），但对仅 DM 患者没有影响。联合治疗的降低作用最显著。
与 GFR 正常的 DM 患者相比，CKD 分期 3-4 期的 DM 患者炎症活动增加。降脂治疗降低了合并 CKD 的 DM 患者的 MCP-1 和 IFNγ 水平，这可能对动脉粥样硬化和糖尿病肾病的进展都有益。
