Efficacy of N-Acetylcysteine in Preventing Acute Kidney Injury

Introduction:

Acute kidney injury also known as acute renal failure, is a postoperative complication after heart surgery, persistent infection, prolonged hospitalization, or administering certain contrast media or dye for diagnostic purposes. It is a sudden decrease in kidney function. It is a multifactorial syndrome. It leads to a prolonged hospital stay, the use of dialysis, chronic kidney disease, and death. Many factors related to the kidney or others lead to the development of acute kidney infection after cardiac surgery.

Those factors are renal ischemia (reduced blood flow to the kidneys), reperfusion (restoration of the blood flow to the previously ischemic tissue), trauma, inflammation, stress, hemolysis ( rupture of the blood cells), cholesterol emboli (small cholesterol crystals entering the bloodstream), or nephrotoxins (toxins that destroy the kidneys). The risk of developing acute kidney infection is increased in individuals with advanced age, chronic kidney disease (CKD), diabetes, heart failure, and those patients who undergo complex surgeries with prolonged cardiopulmonary bypass time, a technique during certain surgeries in which a machine works like the heart and lungs temporarily to support surgery on the heart and blood vessels.

The incidence of acute kidney infection occurs in around 18 % of patients undergoing heart surgery, and approximately 2% - 6% of them require RRT or renal replacement therapy. The mortality rate after cardiac surgery increases with even a little bit of rising creatinine levels. The development of acute kidney injury after cardiac surgery is a fatal outcome that is increasing in incidence. Few reports suggest that perioperative use of certain drugs like fenoldopam, clonidine, natriuretic peptides, sodium nitroprusside, or elective pre-op hemodialysis may prevent the development of acute kidney injury, but none of them have been found to be efficient.

What Is N-Acetyl Cysteine or NAC?

N-acetylcysteine is an FDA-prescribed medicine. It is an antioxidant, anti-inflammatory, and vasodilatory (causing widening of the blood vessels) medicine that might help prevent cancer. It can regulate glutathione (an antioxidant and detoxifying agent). It is also used to treat paracetamol poisoning, cough, and colds as a mucous-breaking agent. N-acetylcysteine has been tested for its role in the prevention of postoperative acute kidney infection and contrast-induced acute kidney infection (CI-AKI) by measuring the change in serum creatinine levels before and after the administration of the drug.

Serum creatinine is the cheapest and the most widely approved marker of kidney function. Serum creatinine is a byproduct of muscle contraction that determines how well the kidneys are functioning. It decreases the incidence of acute kidney infection by reducing the production of free radicals, reducing the levels of cytokines that are inflammatory in nature, and improving the ischemia-reperfusion injury - the damage to the tissues when the blood supply to the tissues is restored after being devoid of oxygen for some time). The efficiency of N-acetylcysteine has been researched in many clinical trials. However, the results were contradictory.

How Does N-Acetyl Cysteine Prevent Acute Kidney Infection?

Acute kidney injury after certain surgeries is a possible complication usually associated with mortality. NAC is an alternative therapy that might help in preventing acute kidney injury. It weakens certain mechanisms that lead to acute kidney injury during cardiac surgery, such as inflammation, restricted blood flow to the kidneys, and injuries due to damage-causing compounds. For patients receiving contrast media or dye for various diagnostic and therapeutic procedures, CI-AKI is the possible outcome causing increased hospitalization.

N-Acetylcysteine has been found to prevent acute kidney injuries in postoperative acute kidney infection and contrast-induced acute kidney infection (CI-AKI) by changing the serum creatinine levels. It has also been found to preserve the function of kidneys during kidney injury caused by a low blood supply. Considering its low cost, none or few side effects, and easy ways of administration, NAC has been recommended for use by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. A systematic review from the Agency of Healthcare Research and Quality also accepted its use for CI-AKI prophylaxis- contrast-induced acute kidney injury. NAC has been found to reduce oxidative stress and acute kidney failure caused by ischemic reperfusion.

What Was the Result of the Studies?

Several studies, meta-analysis, trial sequence analyses, randomized control trials, etc., have been carried out to understand the effect of N-acetylcysteine on kidney injury. More than forty trials have been performed in the last ten years but with inconsistent results.

The reason behind these contradictory findings could be related to the method of trials.

• The meta-analysis studies found that the incidence of developing acute kidney injury in post-operative heart patients who received N-acetylcysteine via the bloodstream (i.v) is much lesser as compared to the ones who received it orally. When administered orally, the drug goes to the digestive system first, decreasing its concentration in the bloodstream. The dose of I.V administration is much higher than that of oral administration.

• Intravenous administration of N-acetylcysteine was also found to reduce the incidence of arrhythmia (improper heartbeat) after cardiac surgeries by reducing inflammation.

• It has also been reported to improve kidney aging and kidney fibrosis.

• Several other studies have also ruled out the hypothesis that preoperative administration of N-acetylcysteine reduces the incidence of acute kidney injury or increases serum creatinine after surgery.

• A decreased rate of developing acute kidney infection has been found in patients with borderline chronic cardiac disease if administered with intravenous N-acetylcysteine.

• However, there was no significant decrease in mortality, heart attacks, heart failure, length of hospital stay, and RRT- renal replacement therapy (a therapy that replaces the blood-filtering function of the kidneys).

Conclusion:

In a nutshell, the different studies suggest that intravenous administration of N-acetylcysteine after surgery may reduce the rate of developing acute kidney injury but might not reduce mortality, heart attacks, etc. The oral administration of the drug is not effective in patients after heart surgery. Further research is needed to determine the correct dose and administration of N-acetylcysteine before recommending its use after cardiac surgery.