N-acetylcysteine reduces urinary albumin excretion following contrast administration: evidence of biological effect.

BACKGROUND There are conflicting results regarding the effectiveness of N-acetylcysteine (NAC) in attenuating contrast-induced nephropathy (CIN). NAC administration independently reduces serum creatinine, potentially confounding studies utilizing creatinine-based endpoints. Albuminuria is a marker of renal injury and spot urine albumin: creatinine ratios (ACR) reflect 24-h urine albumin excretion. We performed a pre-specified secondary analysis from our published negative randomized control trial of NAC for prevention of CIN, to determine if NAC administration reduces albuminuria after contrast exposure following cardiac catheterization. METHODS We included study patients who had paired urine specimens obtained pre- and post-cardiac catheterization. Baseline characteristics were compared using the chi square test or Mann-Whitney U-test, as appropriate. Changes in ACR were evaluated using binomial exact test. The effect of NAC on post-cardiac catheterization changes in ACR ratio was evaluated by ordinal logistic regression. RESULTS A total of 125 patients met inclusion criteria (pre- and post-catheterization urinalysis within 7 days). Baseline characteristics neither differ between NAC and placebo groups, nor were they different from those who were excluded. Among the patients receiving NAC, 10.7% improved their ACR ratio and 7.1% worsened; in contrast, in patients on placebo only 4.3% improved, while 21.7% worsened (P=0.015). Change in ACR ratio was not associated with change in kidney function as measured by calculated creatinine clearance or GFR. CONCLUSIONS The results of this analysis suggest NAC may attenuate contrast-induced glomerular or tubular injury, as defined by albumin excretion, and appears to be independent of any effect on creatinine-derived measures of kidney function. Larger studies are required to confirm this observation.

[1]  A. Levin,et al.  N-acetylcysteine for prevention of radiocontrast induced nephrotoxicity: the importance of dose and route of administration , 2005, Heart.

[2]  K. Shojania,et al.  Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis. , 2004, The American journal of medicine.

[3]  P. Mathieson The cellular basis of albuminuria. , 2004, Clinical science.

[4]  K. Tuttle Cardiovascular Implications of Albuminuria , 2004, Journal of clinical hypertension.

[5]  R. Toto Microalbuminuria: Definition, Detection, and Clinical Significance , 2004, Journal of clinical hypertension.

[6]  Yasuhiro Yamamoto,et al.  Correlation of Glomerular Permeability, Endothelial Injury, and Postoperative Multiple Organ Dysfunction , 2004, Surgery Today.

[7]  A. Levin,et al.  A randomized controlled trial of intravenous N-acetylcysteine for the prevention of contrast-induced nephropathy after cardiac catheterization: lack of effect. , 2004, American heart journal.

[8]  M. Tonelli,et al.  Systematic review of the impact of N-acetylcysteine on contrast nephropathy. , 2004, Kidney international.

[9]  C. Poole,et al.  N-acetylcysteine for the prevention of radiocontrast induced nephropathy: a meta-analysis of prospective controlled trials. , 2004, Journal of the American Society of Nephrology : JASN.

[10]  B. Krämer,et al.  The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable. , 2004, Journal of the American Society of Nephrology : JASN.

[11]  B. Jaber,et al.  Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomized, controlled trials. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[12]  P. O'Malley,et al.  Meta-analysis of randomized clinical trials on the usefulness of acetylcysteine for prevention of contrast nephropathy. , 2003, The American journal of cardiology.

[13]  J. Morrow,et al.  The effect of N-acetylcysteine on renal function, nitric oxide, and oxidative stress after angiography. , 2003, Kidney international.

[14]  G. Eknoyan,et al.  National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification , 2003, Annals of Internal Medicine.

[15]  D. de Zeeuw,et al.  How to measure the prevalence of microalbuminuria in relation to age and gender? , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[16]  C. Tsalamandris,et al.  Albumin to creatinine ratio: a screening test with limitations. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[17]  M. Bell,et al.  The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions. , 2002, Journal of the American College of Cardiology.

[18]  J. Coresh,et al.  Microalbuminuria in the US population: third National Health and Nutrition Examination Survey. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[19]  W. Keane,et al.  Proteinuria and cardiovascular disease. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[20]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[21]  G. Taylor,et al.  Oxygen free radicals and contrast nephropathy. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[22]  W. O’Neill,et al.  Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. , 1997, The American journal of medicine.

[23]  M. H. Gault,et al.  Prediction of creatinine clearance from serum creatinine. , 1975, Nephron.