Rosuvastatin plus N Acetylcysteine to Prevention of Contrast Induced Acute Kidney Injury in Patients with Low Mehran Risk Score

Abbreviations

CIN: Contrast Induced Nephropathy; RCTs: Randomized Clinical Trials; CrCl: Creatinine Clearance; NYHA: New York Heart Association.

Introduction

Rosuvastatin is high-intensity statins commonly used in patients with very high or high risk atherosclerotic cardiovascular disease. At same time also have pleiotropic effects additionally to the lipid-lowering effect. Rosuvastatin hydrophilic form of statin and may be better potential for prevention of contrast induced nephropathy (CIN) than other statin forms, probably owing to stronger anti-inflammatory effect and longer plasma half-life than other statins. Contrast- induced acute kidney injury is the major risk for hospital acquired acute renal failure and is associated with high mortality rate may be led to persistent worsening of renal function and end stage renal disease [1, 2].

Several medications have examined how to prevent contrast induced acute renal injury. Among patients who need contrast media for diagnostic or therapeutic procedures. Studies using N-acetylcysteine have been debated widely [3]. But high dose N-acetylcysteine shown clinical efficacy for prevent contrast induced acute kidney injury [4].

Many randomized clinical trials (RCTs) have failed to show beneficial effects of statin for prevent contrast induced acute kidney injury [5, 6, 7, 8, 9, 10]. Conversely, some trials have suggested that pretreatment of rosuvastatin can reduce the prevalence of CIN in patients undergoing PCI because it can reduce inflammation and oxidative stress to a greater extent.

Statins have renoprotective effects in patients with kidney disease [11]. The latest report of European Society of Cardiology guidelines on myocardial revascularization advises the use of statins to prevent Contrast induced acute kidney injury, especially in patients with high-risk for acute renal injury after contrast administration [12]. Hence, in our prospective trial we make comparison between high dose rosuvastatin versus rosuvastatin plus N acetylcysteine to prevention of Contrast induced kidney injury in patients with low Mehran risk score who undergoing elective PCI at Alshifa hospital in Gaza – Palestine.

Results

Baseline clinical characteristics were well balanced between two groups, total male 72 patients, total female 28 patients. Mean age 58+9.5 years. Mehran risk score < 5 was in 85% patients, Mehran risk score 5-16 was in 15% of the patients (Table 1).

Discussion

Our study is randomized, prospective trial to evaluate the efficacy of high intensity statin therapy plus N-acetylcysteine for the prevention of contrast induced kidney injury in patients with mild-to-moderate Mehran risk score who undergoing PCI comparison to statin alone.

In our trial, we observed that periprocedural administration of rosuvastatin, 40 mg daily for a short duration (3 days), and N acetylcysteine 1200 mg (2 days) suggesting that a short course of oral statin and NAC may reduce the incidence of contrast induced kidney injury after contrast medium injection in these patients. But rosuvastatin 40 mg daily for 3 days alone doesn’t reduction creatinine level after PCI. These results are of clinical significance because contrast induced acute kidney injury is a severe complication in patients with previous have impaired renal function.

Despite of many metanalysis suggested benefit of statin pretreatment in prevention of contrast-induced nephropathy [14]. Kandula P, et al. [5] reported an observational study on 239 patients who received statins and 114 subjects who not received statins. They Toso A, et al. [15] suggested that statin therapy was not related to reduce contrast induced nephropathy prevention (P= 0.12) a short-time administration of high doses of atorvastatin before and after contrast medium exposure, in addition to intravenous hydration and oral N-acetylcysteine, does not decrease CIN occurrence in patients with pre-existing chronic renal disease.

Han Y, et al. [16] enrolled patients with type 2 diabetes mellitus or kidney disease stage 2 or 3 from 53 clinical centers in China. Patients were randomly divided to receive 10 mg rosuvastatin per day for 2 days before and 3 days after the diagnostic angiography procedure or 1 placebo. Hydration with isotonic saline was given according to treating doctor.

The primary end point was contrast-induced Acute kidney injury.

The incidence of contrast-induced Acute kidney injury was significantly lower among patients in rosuvastatin group than those in the placebo group (2.3% vs 3.9%, P=0.01). In this trial low dose statin was used, and hydration not routine for all patients but was given according to treating physician. In our trial we used 40 mg rosuvastatin and routine hydration for all patients.

In the PRATO-ACS trial, Leoncini M, et al. [17], evaluates the effects of rosuvastatin on contrast induced acute kidney injury in patients with a non-ST elevation acute coronary syndrome. Patients were randomly to receive high dose rosuvastatin (40 mg on hospital admission then 20 mg per day until hospital discharge) or to placebo before undergoing angiography. All patients were received isotonic saline and N-acetylcysteine.

The incidence of contrast induced acute kidney injury was significantly lower among patients treated with rosuvastatin than those in the placebo group (6.7% vs 15.1%, P=0.003). This study similar to our trial but in our trial control group was used 40 mg rosuvastatin and hydration.

Study Limitations

First, most of patients of our trial (85%) are low risk according to Mehran risk score. Second, this study the sample size was small. Small a sample size led to further limitations in statistical significance of subgroup data. Third, in addition, we used routine pre-treatment with N acetylcysteine and hydration was used in all patients. The association between N acetylcysteine and rosuvastatin may not rule out the possibility of an interaction or a synergistic effect. Thus, results from previous studies and from our study strongly suggest that use of statins and N acetylcysteine can reduce contrast induced acute kidney injury.

Conclusion

Rosuvastatin at 40 mg per day for 3 days plus N acetylcysteine 1200 mg twice daily for 2 days compared with Rosuvastatin alone significant decrease in creatinine level but no significant difference was seen in creatinine clearance and BUN but in patients with low Mehran risk.

Declaration of Competing Interest: There is no conflict of interest.

Acknowledgments: The author would like to acknowledge patients who participated in this study.

Declaration of Patient Consent: The authors certify that they have obtained all appropriate patient consent forms.

Author’s Contribution: Mohammed habib (MH) gave a substantial contribution to the conception and design of the work, gave a substantial contribution of data and gave a substantial contribution to the acquisition, analysis, or interpretation of data for the work.

Financial Support and Sponsorship: Nil.