Acetylcysteine did not reduce kidney injury in at-risk patients having vascular angiography

Saklayen MG. — Tue, 17 Jan 2012 00:00:00 GMT

Question

Does acetylcysteine reduce risk for contrast-induced acute kidney injury (CI-AKI) in at-risk patients having coronary or peripheral vascular angiography?

Methods

Design

Randomized placebo-controlled trial (Acetylcysteine for Contrast-induced nephropathy Trial [ACT]). ClinicalTrials.gov NCT00736866.

Allocation

Concealed.*

Blinding

Blinded (patients, health care staff, data collectors, and outcome assessors).*

Follow-up period

48 to 96 hours and 30 days.

Setting

46 sites in Brazil.

Patients

2308 patients (mean age 68 y, 62% men) who were having an intravascular angiographic procedure (coronary or peripheral arterial diagnostic angiography or percutaneous intervention) and had ≥ 1 risk factor for CI-AKI: > 70 years of age, chronic renal failure (stable serum creatinine levels > 132.6 µmol/L [1.5 mg/dL]), diabetes mellitus, heart failure, hypotension, or left ventricular ejection fraction < 0.45. Exclusion criteria included dialysis and primary angioplasty after ST-segment elevation myocardial infarction.

Intervention

Oral acetylcysteine, 1200 mg every 12 hours, given twice before and twice after angiography (n = 1172), or placebo (n = 1136).

Outcomes

CI-AKI (25% increase in serum creatinine level at 48 to 96 h after angiography), composite endpoint of death or need for dialysis, components of the composite endpoint, cardiovascular (CV) death, and adverse events. 2300 patients were needed to detect a 30% relative risk reduction from 15% in CI-AKI at 48 to 96 hours (90% power, 2-tailed α = 0.05).

Patient follow-up

> 98% (intention-to-treat analysis).

Main results

Acetylcysteine did not reduce CI-AKI, all-cause or CV deaths, need for dialysis, or serious adverse events more than placebo (Table). Results for CI-AKI were similar in prespecified subgroups including age > 70 years, sex, serum creatinine level > 132.6 µmol/L (1.5 mg/dL), volume of contrast agent ≥ 140 mL, and presence of diabetes.

Conclusion

In at-risk patients having vascular angiography, acetylcysteine did not reduce risk for contrast-induced acute kidney injury.

Acetylcysteine vs placebo in patients having angiography who are at risk for contrast-induced acute kidney injury (CI-AKI)†

OutcomesAcetylcysteinePlaceboRRI (95% CI) at 48 to 96 hCI-AKI12.75%12.69%0% (−19 to 25)RRR (CI) at 30 dDeath or need for dialysis‡2.2%2.3%3% (−68 to 44)Cardiovascular death1.5%1.6%1% (−89 to 49)Serious adverse events§1.3%2.2%42% (−10 to 69)†Abbreviations defined in Glossary. RRI, RRR, and CI calculated from data in article.‡Death (2.0% vs 2.1%, P = 0.92); need for dialysis (0.3% vs 0.3%, P = 0.86).§Including stroke, myocardial infarction, pneumonia, sepsis, and acute pulmonary edema.

The RenalGuard system reduced kidney injury more than a control system in high-risk patients

Saklayen MG. — Tue, 17 Jan 2012 00:00:00 GMT

Question

Does hydration controlled by the RenalGuard system prevent contrast-induced acute kidney injury (CI-AKI) in high-risk patients having angiography or angioplasty?

Methods

Design

Randomized controlled trial (Renal Insufficiency After Contrast Media Administration Trial II [REMEDIAL II]). ClinicalTrials.gov NCT01098032.

Allocation

{Concealed}*.†

Blinding

Blinded (outcome adjudication committee).†

Follow-up period

1 month.

Setting

4 interventional cardiology centers in Italy.

Patients

294 patients (mean age 76 y, 65% men) who were scheduled for angiography or angioplasty, had chronic kidney disease, and had an estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m² or a contrast neuropathy risk score ≥ 11 (based on hypotension, intra-aortic balloon pump support, heart failure, age > 75 y, diabetes mellitus, eGFR < 60 mL/min/1.73m², preexisting anemia, and contrast agent volume). Exclusion criteria included dialysis; acute myocardial infarction or pulmonary edema; cardiogenic shock; multiple myeloma; use of iodinated contrast agent in the past 48 hours; and use of sodium bicarbonate, theophylline, dopamine, mannitol, or fenoldopam.

Intervention

Intravenous (IV) N-acetylcysteine (NAC), 1500 mg in 1 L of saline, controlled by the RenalGuard system (PLC Medical Systems Inc., Franklin, Massachusetts, USA), which manages urine output and fluid balancing, plus IV furosemide, 0.25 mg/kg to a target urine flow of ≥ 300 mL/h, started before and continued until after the procedure (n = 147); or IV sodium bicarbonate, 154 mEq/L, started before and continued until after the procedure, plus IV NAC, 1200 mg in 100 mL of saline, given during the procedure, and oral NAC, 1200 mg, given twice daily on the day before and the day of contrast agent administration (n = 147).

Outcomes

CI-AKI (≥ 26.5 µmol/L [0.3 mg/dL] increase in serum creatinine level 48 h after contrast agent given or need for dialysis), acute renal failure needing dialysis, and major adverse events (death, renal failure needing dialysis, and acute pulmonary edema).

Patient follow-up

99%.

Main results

The main results are in the Table.

Conclusion

In high-risk patients, the RenalGuard system using saline plus N-acetylcysteine and furosemide was better than sodium bicarbonate plus N-acetylcysteine for preventing contrast-induced acute kidney injury.

Hydration using the RenalGuard system vs control in high-risk patients having angiography or angioplasty‡

OutcomesRenalGuardControlRRR (95% CI)NNT (CI)CI-AKI11%21%47% (6 to 72)11 (7 to 76)In-hospital renal failure needing dialysis0.7%4.1%83% (−12 to 98)Not significantMajor adverse events at 1 mo§6.8%9.6%29% (−52 to 67)Not significant‡CI-AKI = contrast-induced acute kidney injury; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from odds ratios and control event rates (CI-AKI and in-hospital renal failure needing dialysis) or intervention and control event rates (major adverse events) in article.§Death (4.1% vs 4.1%, P = 1.00); renal failure needing dialysis (0.7% vs 4.8%, P = 0.03); and acute pulmonary edema (2.1% vs 0.7%, P = 0.62).

Annals of Internal Medicine: Acute Kidney Injury Topic Collection

Acetylcysteine did not reduce kidney injury in at-risk patients having vascular angiography

The RenalGuard system reduced kidney injury more than a control system in high-risk patients