N-acetylcysteine to Prevent Renal Failure

Study Overview
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Brief Summary
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The purpose of this study is to determine the possible effect nephroprotective of N-acetylcysteine in patients with chronic kidney disease undergoing elective coronary artery bypass grafting by serial evaluation of renal function and to evaluate whether treatment reduces cardiac mortality, cardiac events and Global mortality, if it interferes with oxidative stress and inflammation and the need for dialysis.

Detailed Description
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Renal failure is a serious and relatively frequent complication of cardiac surgery was observed, especially in diabetics and those with pre-existing renal dysfunction. Given that oxidative stress is elevated in diabetics and in renal and heart, it is reasonable to speculate on its involvement in the pathophysiology of this complication. It is unknown whether the incidence of postoperative renal failure can be reduced by antioxidants. N-acetylcysteine (NAC) is an antioxidant that prevents nephropathy induced by contrast medium and aminoglycosides and increases intracellular levels of cyclic guanosine monophosphate, acting as a vasodilator and platelet inhibitor. Based on a knowledge of the pathophysiology of ARF, several interventions have been attempted over the past decades. However, various measures employed successfully in the prevention of experimental ARF did not result in success in clinical practice. Much of this failure is probably due to the difference between the experimental models of ARF that encountered in the clinic. Other factors that should be considered, and that may explain the poor results in clinical trials are: the time of use of the drug, dosage and route of administration, are not always adequate. From the data in the literature, it remains doubtful whether the protective role of NAC is limited only to contrast nephropathy or whether it could have application in other clinical situations in which oxidative stress and vasoconstriction are determinants of injury, as occurs, for example, in CABG surgeries. NAC is a drug of low cost and low toxicity, this paper intend to assess its role as prophylaxis of renal dysfunction in the postoperative period of CABG in patients with chronic kidney disease stages 3 and 4 (GFR between 15 and 59 mL/min/1, 73 m2 of body surface).

Official Title
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N-acetylcysteine to Prevent Renal Failure in Patients With Chronic Kidney Disease Undergoing Coronary Artery Bypass Surgery

Conditions
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Kidney Failure, Acute, Oxidative Stress Induction

Intervention / Treatment
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* Drug: N-acetylcysteine
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients aged 30 to 80 years old of both sexes indicated for elective CABG with glomerular filtration rate, assessed with the MDRD <60 mL/min/1, 73 m2 and> 15 mL / min / 1.73 m2 body surface Exclusion Criteria: patients on chronic dialysis or with creatinine> 5 mg / dL preoperatively; individuals allergic or intolerant to N-acetylcysteine pregnant women patients with cancer patients underwent re-surgery within the first 72 hours postoperatively

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-Acetylcysteine<br>N-acetylcysteine is administered at a dose of 150mg/kg in 500mL of saline EV in 1 hour followed by a dose of 50mg/kg in 500 mL of saline IV within 6 hours, beginning the infusion together to surgery. | Drug: N-acetylcysteine<br>* N-acetylcysteine is administered at a dose of 150mg/kg in 500mL of saline EV in 1 hour followed by a dose of 50mg/kg in 500 mL of saline IV within 6 hours, beginning the infusion together to surgery.<br>* Other names: Fluimucil;|
| Placebo Comparator: Control<br>This group will receive only the infusion of saline in the same doses and infusion rate. | Drug: Control<br>* The control group will receive only the infusion of saline in the same doses and infusion rate.<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in glomerular filtration defined by at least 30% compared to preoperative levels . |  | Within the first 72 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Up 50% of preoperative levels of serum creatinine. |  | Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively. | 
| Death from any cause. |  | Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively. | 
| Need for dialysis |  | Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively. | 
| Cardiovascular morbidity. |  | Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively. | 
| Increased levels of Cystatin C. |  | Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively. | 
| Increased levels of NGAL. |  | Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively. | 
| Increased levels of isoprostane. |  | Within the first 72 hours after surgery and cardiovascular morbidity and all-cause mortality at thirty days post-operatively. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-acetylcysteine, Myocardial Revascularization, Acute Renal Failure, Oxidative Stress