Can N-acetylcysteine (NAC) be used to decrease creatinine levels in patients with impaired renal function?

N-Acetylcysteine Does NOT Decrease Creatinine or Improve Renal Function

N-acetylcysteine (NAC) should not be used to decrease creatinine levels or improve renal function in patients with impaired kidney function. The highest quality evidence demonstrates no benefit for preventing acute kidney injury in any clinical setting, and any observed creatinine decreases represent laboratory artifact rather than true improvement in kidney function.

Guideline Recommendations Against NAC Use

The KDIGO guidelines provide the strongest evidence against NAC:

• NAC is not recommended for prevention of postsurgical AKI (Grade 1A recommendation) 1
• NAC should not be used to prevent AKI in critically ill patients with hypotension (Grade 2D recommendation) 1
• The evidence against NAC use in critically ill patients and post-surgery is even stronger than the already controversial evidence for contrast-induced nephropathy prevention 1

The ACT Trial: Definitive Evidence of No Benefit

The Acetylcysteine for Contrast Nephropathy Trial (ACT) represents the highest quality evidence and directly contradicts any benefit of NAC:

• This double-blinded, placebo-controlled trial of 2,308 patients showed identical rates of contrast-induced AKI in both groups (12.7% vs 12.7%) 1
• No difference was detected in the combined secondary endpoint of mortality or need for dialysis (hazard ratio 0.97; 95% CI 0.56-1.69) 1
• No subgroup benefit was found, including in patients with diabetes or estimated creatinine clearance <60 mL/min 1

The Canadian Society of Nephrology explicitly states that the results of ACT do not support continuing recommendations for NAC use to prevent contrast-induced AKI 1

Meta-Analysis Reveals Bias in Earlier Studies

When trials are stratified by methodological quality, the evidence becomes clear:

• Low-quality studies showed apparent benefit (RR 0.63; 95% CI 0.47-0.85) 1
• High-quality studies meeting all methodological criteria showed no effect (RR 1.05; 95% CI 0.73-1.53) 1
• The benefits reported in prior studies were confined to trials with high risk of bias 1

The Creatinine Artifact Problem

NAC may artificially lower serum creatinine measurements without improving actual kidney function:

• A systematic review found NAC causes a small but significant decrease in serum creatinine (WMD -2.80 μmol/L; 95% CI -5.6 to 0.0) 2
• The effect was greater with non-Jaffe methods (WMD -3.24 μmol/L) and particularly with intravenous NAC (WMD -31.10 μmol/L) 2
• Cystatin C levels did not change after NAC administration, suggesting analytic interference rather than true improvement in kidney function 2

However, this artifact effect is inconsistent across studies:

• Two studies in stage 3 CKD patients found no effect of NAC on either serum creatinine or cystatin C 3, 4
• One study in cardiac surgical patients found no artifactual lowering of creatinine using the Jaffé method 5

Current Guideline Consensus

The most recent and authoritative guidelines explicitly recommend against NAC:

• The American College of Cardiology Foundation/American Heart Association states that NAC administration is not useful for prevention of contrast-induced AKI (Level of Evidence: A) 6
• The European Society of Cardiology classifies NAC as Class III (not indicated) based on Level A evidence 6
• The American College of Cardiology recommends focusing on proven strategies: proper hydration and adjustment of contrast dose to renal function 1

What Actually Works for Renal Protection

Instead of NAC, use evidence-based strategies:

• Hydration with isotonic saline (1.0-1.5 mL/kg/hour) for 3-12 hours before and 6-24 hours after contrast exposure (Class I recommendation) 6, 7
• Minimize contrast volume to <350 mL or <4 mL/kg, or maintain contrast volume/creatinine clearance ratio <3.7 6
• Use low-osmolar or iso-osmolar contrast media (Class I recommendation) 6
• Consider short-term high-dose statin therapy (Class IIa recommendation) 6

Clinical Bottom Line

NAC does not decrease creatinine through improvement in renal function and should not be used for this purpose. Any observed decreases in creatinine likely represent laboratory interference, particularly with non-Jaffe assays and intravenous administration 2. The highest quality evidence from the ACT trial and updated meta-analyses demonstrate no benefit for preventing AKI or improving clinical outcomes 1. Focus instead on proven renal protective strategies including adequate hydration, contrast minimization, and avoidance of nephrotoxic medications 6, 7.