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Diuresis-hydration prevents contrast-induced nephropathy, N-acetylcysteine does not

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – N-acetylcysteine is increasingly used to prevent contrast-induced nephropathy (CIN) but it is not effective, according to a paper in JACC: Cardiovascular Interventions for January, while another article in the journal indicates that forced diuresis with furosemide along with replacement hydration is effective.

The authors of the latter report comment, “Our study also emphasizes the close relationship between CIN and poor clinical outcome, and the benefit of preventing this complication.”

Dr. Giancarlo Marenzi, with the Centro Cardiologico Monzino at the University of Milan, Italy, and colleagues point out that IV hydration is the cornerstone of CIN prevention, but this is sometimes suboptimal in patients with chronic kidney disease because of the risk of overhydration.  Previous studies have shown that forced diuresis in this setting prevented overhydration while concurrent IV fluid replacement matched to urine output prevented dehydration.

In the current study, the investigators used a device designed for that purpose.  “The Renal-Guard System is capable of delivering sterile replacement solution to a patient in an amount matched to the volume of urine produced by the patient, avoiding hypovolemia and fluid overload,” they explain.

The team randomized 170 patients with chronic kidney disease undergoing coronary procedures to furosemide with matched hydration using the device or to a control group given standard IV isotonic saline hydration.

Patients in the furosemide-hydration group were first given a 250-mL IV fluid bolus followed by 0.5 mg/kg furosemide.  When the urine output and matched fluid replacement surpassed 300 mL per hour, the coronary procedure was begun.   Fluid replacement matched to output was maintained during the procedure and for 4 hours afterwards.

The main outcome measure was the development of CIN, defined as a rise in serum creatinine of at least 25% or 0.5 mg/dL over baseline.  This occurred in 18.0% of controls but in only 4.6% of the patients in the furosemide-hydration group (p=0.005), the authors report.

Corresponding rates of a composite of all major post-procedure adverse events (such as acute MI, pulmonary edema, need for dialysis, death etc.) were 20% versus 8%, the report indicates.

“However, this study was not powered to detect differences in clinical outcome,” Dr. Marenzi and colleagues note.  “Thus, this result should be considered preliminary, and the impact of this strategy on meaningful clinical endpoints requires confirmation in larger and multicenter trials,” they conclude.

That study is followed by a report from Dr. Hitinder S. Gurm, at the University of Michigan, Ann Arbor, and colleagues on the contemporary use and effectiveness of N-acetylcysteine for preventing CIN.

The team analyzed data from a multicenter collaborative program in Michigan on 90,578 patients who underwent non-emergent PCI from 2006 through 2009.  They found that N-acetylcysteine was used in 10,574 procedures (11.6%), with the rate increasing from 10.1% at the start of the study period to 13.0% at the end.

The authors identified two propensity-matched cohorts of 8626 patients in each who were given or not given pre-procedural N-acetylcysteine.  Outcomes in these two groups were almost identical.  Specifically, the rates of CIN were 5.5% vs. 5.5%, respectively, while nephropathy requiring dialysis occurred in 0.6% vs. 0.6%, and mortality was 0.6% vs. 0.8%, according to the report.

“The results of our work are strikingly similar to that of the recently presented ACT trial (Acetylcysteine for the prevention of Contrast-induced nephropathy Trial), which found little difference in outcome of patients randomized to NAC (N-acetylcysteine) compared with placebo,” Dr. Gurm and colleagues point out.

“The results of our study combined with those of the ACT trial suggest that this practice should be abandoned,” they conclude.


Prevention of Contrast Nephropathy by Furosemide With Matched Hydration : The MYTHOS (Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy Prevention) Trial

Contemporary Use and Effectiveness of N-Acetylcysteine in Preventing Contrast-Induced Nephropathy Among Patients Undergoing Percutaneous Coronary Intervention

J Am Coll Cardiol Intv 2012;5:90–104.