Renoprotective effects of clarithromycin via reduction of urinary MCP-1 levels in type 2 diabetic patients.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Diabetes and Metabolism, National Hospital Organization, Okayama Medical Center, 1711-1 Tamasu, Kita-ku, Okayama 701-1192, Japan. aitone@okayama3.hosp.go.jp
Atsuhito
A
Tone
Kenichi
K
Shikata
Koichi
K
Nakagawa
Masaaki
M
Hashimoto
Hirofumi
H
Makino
D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000652:urine*; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine*; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011507:Proteinuria / Q000652:urine; D051381:Rats
D000900:Anti-Bacterial Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017291:Clarithromycin