Department of Diabetes and Metabolism, National Hospital Organization, Okayama Medical Center, 1711-1 Tamasu, Kita-ku, Okayama 701-1192, Japan.
Clin Exp Nephrol. 2011 Feb;15(1):79-85. doi: 10.1007/s10157-010-0357-1. Epub 2010 Nov 3.
Recent studies have shown the involvement of microinflammation in the pathogenesis of diabetic nephropathy. We previously demonstrated that erythromycin, one of the macrolides, ameliorated renal injury via anti-inflammatory effects in experimental diabetic rats. We conducted an open randomized controlled pilot study to investigate the renoprotective effect of clarithromycin for diabetic nephropathy in type 2 diabetic patients manifesting albuminuria.
Sixteen patients were randomly assigned to the control (n = 8) or the CAM group in which they received 200 mg/day of clarithromycin (n = 8). At the beginning of the study and after 3 months of investigation, the following parameters were assessed: urinary albumin creatinine ratio (ACR), the levels of serum MCP-1, soluble ICAM-1, IL-18, IL-6 and hs-CRP, and the levels of urinary MCP-1 and IL-18.
The changes in urinary ACR were significantly improved (P = 0.039), and serum creatinine levels showed a decreasing trend (P = 0.053) in the CAM group compared with the control group. Urinary MCP-1 levels were significantly reduced in the clarithromycin-administrated group (P = 0.009). However, there was no significant difference in other proinflammatory markers. A significant positive correlation was obtained between the post-to-pre-urinary ACR and the post-to-pre-urinary MCP-1 ratio(r = 0.526, P = 0.043). In the CAM group, the changes of serum creatinine also showed a significant positive correlation with those of urinary ACR, urinary MCP-1, urinary IL-18 and serum levels of soluble ICAM-1.
The results from our study suggest that clarithromycin may attenuate the production of renal MCP-1 in type 2 diabetic patients, resulting in amelioration of urinary ACR via anti-inflammatory effects. Modulation of microinflammation with clarithromycin may provide a new approach for diabetic nephropathy.
最近的研究表明,微炎症参与了糖尿病肾病的发病机制。我们之前的研究表明,大环内酯类药物之一的红霉素通过在实验性糖尿病大鼠中发挥抗炎作用来改善肾脏损伤。我们进行了一项开放性随机对照试验,以研究克拉霉素对表现出蛋白尿的 2 型糖尿病患者糖尿病肾病的肾脏保护作用。
将 16 名患者随机分配至对照组(n=8)或 CAM 组(n=8),CAM 组患者每天服用 200mg 克拉霉素。在研究开始时和 3 个月的研究后,评估以下参数:尿白蛋白肌酐比(ACR)、血清单核细胞趋化蛋白-1(MCP-1)、可溶性细胞间黏附分子-1(sICAM-1)、白细胞介素-18(IL-18)、白细胞介素-6(IL-6)和高敏 C 反应蛋白(hs-CRP)水平,以及尿 MCP-1 和 IL-18 水平。
与对照组相比,CAM 组的尿 ACR 变化明显改善(P=0.039),血清肌酐水平呈下降趋势(P=0.053)。克拉霉素治疗组的尿 MCP-1 水平显著降低(P=0.009)。然而,其他促炎标志物无显著差异。尿 ACR 后-前比值与尿 MCP-1 后-前比值之间存在显著正相关(r=0.526,P=0.043)。在 CAM 组中,血清肌酐的变化也与尿 ACR、尿 MCP-1、尿 IL-18 和可溶性 sICAM-1 的血清水平呈显著正相关。
本研究结果表明,克拉霉素可能通过抗炎作用减少 2 型糖尿病患者肾脏 MCP-1 的产生,从而改善尿 ACR。克拉霉素对微炎症的调节可能为糖尿病肾病提供一种新的治疗方法。