title: Prevention of contrast-induced AKI: a review of published trials and the design of the prevention of serious adverse events following angiography (PRESERVE) trial.
abstract: Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial.
authors: Renal Section, VeteransAffairs PittsburghHealthcare System, Pittsburgh, PA 15240, USA. weisbordsd@upmc.edu
authors: Steven D
authors: SD
authors: Weisbord
authors: Martin
authors: M
authors: Gallagher
authors: James
authors: J
authors: Kaufman
authors: Alan
authors: A
authors: Cass
authors: Chirag R
authors: CR
authors: Parikh
authors: Glenn M
authors: GM
authors: Chertow
authors: Kendrick A
authors: KA
authors: Shunk
authors: Peter A
authors: PA
authors: McCullough
authors: Michael J
authors: MJ
authors: Fine
authors: Maria K
authors: MK
authors: Mor
authors: Robert A
authors: RA
authors: Lew
authors: Grant D
authors: GD
authors: Huang
authors: Todd A
authors: TA
authors: Conner
authors: Mary T
authors: MT
authors: Brophy
authors: Joanne
authors: J
authors: Lee
authors: Susan
authors: S
authors: Soliva
authors: Paul M
authors: PM
authors: Palevsky
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control*; D061605:Administration, Intravenous; D000792:Angiography / Q000009:adverse effects; D003287:Contrast Media / Q000009:adverse effects*; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D012107:Research Design / Q000592:standards*; D017693:Sodium Bicarbonate / Q000627:therapeutic use
chemical_list: D003287:Contrast Media; D016166:Free Radical Scavengers; D017693:Sodium Bicarbonate; D000111:Acetylcysteine
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