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.
Levin
Adeera
A
Division of Nephrology, Room 6010, Providence Health Care/Saint Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver V6Z 1Y6, BC, Canada. alevin@providencehealth.bc.ca
Pate
Gordon E
GE
Shalansky
Stephen
S
Al-Shamari
Ali
A
Webb
John G
JG
Buller
Christopher E
CE
Humphries
Karin H
KH
D000111:Acetylcysteine / Q000494:pharmacology*; D000368:Aged; D000418:Albumins / Q000378:metabolism; D000419:Albuminuria / Q000139:chemically induced*; D002404:Catheterization; D003287:Contrast Media / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male
D000418:Albumins; D003287:Contrast Media; D003404:Creatinine; D000111:Acetylcysteine