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.

A randomized controlled trial of intravenous N-acetylcysteine for the prevention of contrast-induced nephropathy after cardiac catheterization: lack of effect.

BACKGROUND: Contrast-induced nephropathy (CIN) after cardiac catheterization is common in patients with preexisting renal dysfunction. Studies of oral acetylcysteine to prevent CIN have produced conflicting results. Intravenous N-acetylcysteine (NAC) has logistic advantages in this setting. The objective of this study was to evaluate, in a blinded, randomized, placebo-controlled fashion, whether intravenous NAC reduced CIN in the setting of cardiac catheterization in patients with preexisting renal insufficiency. METHODS: Patients with renal dysfunction undergoing cardiac catheterization were randomly assigned to intravenous NAC 500 mg immediately before the procedure or placebo. All patients received isotonic saline (200 mL) beforehand, followed by 1.5 mL/kg per hour for 6 hours, unless contraindicated. Exclusion criteria included acute renal failure, creatinine >400 micromol/L, concurrent dialysis, unstable clinical status, and prior NAC use. Baseline creatinine was obtained immediately before the procedure and repeated 2 to 8 days later. The primary end point was the occurrence of CIN defined as a reduction in creatinine clearance from baseline of >5 mL/min (Cockcroft-Gault formula). RESULTS: The study was terminated early because of a determination of futility by the Data Safety Monitoring Committee after enrollment of 487 patients. The median baseline creatinine clearance was 44 mL/min (interquartile range, 33, 55). Median contrast received was 120 mL (interquartile range, 80, 175). Baseline characteristics were similar in the two groups. Altogether, 98 (22.0%) subjects had the primary end point: 23.3% in the NAC group and 20.7% in the placebo arm (P =.57). CONCLUSIONS: In this large, randomized trial, enrolling a high-risk group of patients with impaired renal function, intravenous NAC was ineffective in preventing CIN.

Collapsing glomerulopathy coexisting with membranous glomerulonephritis in native kidney biopsies: a report of 3 HIV-negative patients.

Collapsing glomerulopathy (CG), a variant of idiopathic focal segmental glomerulosclerosis (FSGS), can occur in both human immunodeficiency virus (HIV)-positive and HIV-negative patients. Idiopathic membranous glomerulonephritis (MGN) has been reported to coexist with FSGS, but rarely with CG. We report 3 HIV-negative patients (2 men, 1 woman) who developed nephrotic syndrome secondary to MGN complicated by CG, with relatively rapid disease progression despite aggressive therapy.

Isolated renal giant cell arteritis.

Giant cell arteritis, which most commonly affects the temporal arteries, may involve intrarenal vessels and may be associated with a variety of renal lesions, including necrotizing arteritis, necrotizing glomerulonephritis, granulomatous glomerulonephritis, and membranous glomerulopathy. Isolated giant cell arteritis of the kidney is a rare cause of renal failure. We report a case of a previously healthy 54-year-old white woman who presented with nonoliguric renal failure and a 4-week history of persistent low-grade fever associated with diffuse mild myalgias. She had no history of previous renal or neurologic disease and denied any headaches or visual disturbances. Antinuclear antibody and antineutrophilic cytoplasmic antibody were negative. Renal biopsy revealed noncaseating granulomatous infiltration of arterial and arteriolar walls, a patchy mononuclear cell interstitial infiltrate, and no significant glomerular changes. Treatment with prednisone resulted in dramatic improvement of renal function.