Trimetazidine in the prevention of contrast-induced nephropathy after coronary procedures

Abstract

Objective: To evaluate the efficacy of trimetazidine (TMZ) in the prevention of contrast-induced nephropathy (CIN) in patients with high serum creatinine levels undergoing coronary angiography/angioplasty. Methods: TMZ (20 mg thrice daily) was administered orally for 72 h starting 48 h before the procedure. All patients were given intravenous saline (0.9%) at a rate of 1 ml/kg of body weight per hour for 24 h starting 12 h beforehand. Serum creatinine levels were measured before the procedure, 48 h and 7 days after the procedure. Increase in serum creatinine level exceeding 0.5 mg/day or one quarter of the basal value is considered as CIN. Venous blood samples for serum total antioxidant capacity (TAC) measurement were drawn before and after coronary angiography. Results: Basal serum creatinine levels and TAC were similar in TMZ and control groups. Serum creatinine levels in the control group increased significantly 2 days after the procedure, and returned to the baseline values on the seventh day. However, it did not change significantly on the second day, and even significantly decreased on the seventh day in the TMZ group. CIN developed in 2.5% (1/40) of patients in the TMZ group and in 16.6% (7/42) of patients in the control group (p,0.05). TAC values were not different between treatment groups. Conclusion: TMZ along with isotonic saline infusion is more effective than isotonic saline alone in reducing the risk of CIN in patients with pre-existing renal dysfunction. C ontrast-induced nephropathy (CIN) is a serious complication of coronary angiography that is associated with considerably increased mortality and morbidity, including the need for short-term haemodialysis, extended hospitalisation and permanent impairment of renal function.1 2 CIN after coronary angiography is observed more frequently in patients with chronic renal insufficiency, particularly in patients with diabetes mellitus and/or dehydration and/or congestive heart failure.2-5 Larger doses of contrast medium and intravascular injection of contrast agent are also associated with higher incidence of CIN.6 CIN has been reported to occur in 11-44% of patients with moderate renal insufficiency.2 3 6 7 Pre-existing renal dysfunction is the greatest independent predictor of CIN, and its severity directly correlates with the incidence of CIN. 3 6 8-10 Previous reports suggest that the formation of reactive oxygen radicals, renal medullar ischaemia during reperfusion after contrast-induced vasoconstriction and direct tubular damage secondary to the contrast agent have an important role in the injury mechanisms of CIN.11-14 Many types of prophylaxis regimens have been used in an attempt to prevent CIN. But, to date only hydration with isotonic saline is generally accepted in the prevention of CIN. [14][15][16][17][18] Trimetazidine (TMZ) has been described as a cellular antiischaemic agent. 19 Previous studies demonstrated that TMZ prevents the deleterious effects of ischaemia-reperfusion at both the cellular and the mitochondrial levels, and exert...

The first histopathological evidence of trimetazidine for the prevention of contrast-induced nephropathy

“…24 Recently, Onbaşılı et al were the first to report that TMZ-a cellular anti-ischemic agent-was effective in preventing CIN in patients undergoing coronary procedures. 9 Moreover, Rahman et al confirmed those findings in a study that included 400 patients undergoing coronary angiography; 25 however, neither study was able to identify the physiopathological mechanism of action or was designed to include histopathological findings. As such, the present study aimed to histopathologically analyze the effect of TMZ in preventing CIN and to identify the probable biochemical mechanism of action.…”

“…19 Additionally, these free radicals are thought to cause apoptosis in renal tubule and glomerular cells. 9 Sandhu et al reported earlier that the urinary MDA/creatinine ratio increased following CM infusion and that there might be a relationship between CM infusion and free radical generation. 20 The present study's findings are in agreement with these data, as the MDA level significantly increased and SOD activity significantly decreased after administration of CM in the CM group, as compared to the control group.…”

“…7,8 On the basis of these anti-ischemic and antioxidant properties, Onbaşılı et al previously demonstrated TMZ to be effective in preventing CIN. 9 Thus, we aimed to investigate the prophylactic effects of TMZ against CIN and its relation to oxidant/antioxidant status in rat kidney tissues in a contrast nephropathy induced rat model.…”

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

“…7,8 Trimetazidine or (1-2(2,3,4-trimeoxibenzyl)-piperazine) (TMZ), is used as an anti-anginal agent, selectively inhibits long-chain 3-ketoacyl coenzyme A thiolase (the last enzyme involved in b-oxidation) activity. 9 Its anti-ischemic effects on the kidney have been experimentally assessed in various models including cell culture 10 isolated and perfused kidneys 11 and in vivo. 12,13 TMZ has different pharmacological properties that could be relevant for the prevention of organ damage from I/R by reduction of intracellular acidosis, 14 preservation of ATP production, limitation of inflammatory reaction, and thus of ROS generation.…”

Myocardial Cytoprotector Trimetazidine Mb-Preparat, Increases the Effectiveness of Treatment of Chronic Heart Failure and Coronary Heart Disease

“…Ряд экспериментальных и клинических исследований позволяют предполагать наличие у триметазидина нефро-протективного эффекта [78][79][80][81][82]. Например, при назначе-нии триметазидина МВ за 2 дня до проведения инвазив-ных коронарных процедур (коронарография и др.)…”