Anti-inflammatory renoprotective effect of clopidogrel and irbesartan in chronic renal injury.
Recent evidence suggests that platelet activation and angiotensin II may each contribute to glomerular inflammation and fibrosis. Clopidogrel inhibits platelet activation and may also reduce inflammation. This study investigated the anti-inflammatory and renoprotective effects of clopidogrel and irbesartan in the five-sixths nephrectomy rat model of chronic kidney disease. After 8 wk of treatment, 24-h proteinuria, serum creatinine, and histologic scores of glomerular sclerosis and tubulointerstitial damage were significantly lower in treated compared with untreated rats. Clopidogrel/irbesartan combination therapy had greater effects than either drug alone. Rats that underwent five-sixths nephrectomy had higher markers of platelet activation (plasma GMP-140 and renal cortical fibrin deposition) than sham-operated rats, and clopidogrel attenuated these effects. Clopidogrel and irbesartan similarly reduced the accumulation of ED-1-expressing macrophages in the cortical glomeruli and the interstitium. Combination therapy almost completely abolished macrophage infiltration and attenuated the expression of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, TGF-beta(1), and connective tissue growth factor. In conclusion, combination treatment with clopidogrel and irbesartan, more so than either alone, decreases early renal injury induced by five-sixths nephrectomy by inhibiting renal inflammation.
Tu
Xiaowen
X
Institute of Nephrology of PLA, General Hospital of PLA, 28 Fuxing Road, Beijing 100853, P.R. China. xmchen@public.bta.net.cn.
Chen
Xiangmei
X
Xie
Yuansheng
Y
Shi
Suozhu
S
Wang
Jianzhong
J
Chen
Yunshuang
Y
Li
Jianjun
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D000077144:Clopidogrel; D003404:Creatinine / Q000097:blood; D006973:Hypertension / Q000517:prevention & control; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000517:prevention & control*; D009392:Nephrectomy; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D051381:Rats; D013777:Tetrazoles / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014947:Wounds and Injuries / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D003404:Creatinine; D000077405:Irbesartan; D013988:Ticlopidine