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Original research article
Pharmacological interventions for the prevention of contrast-induced acute kidney injury in high-risk adult patients undergoing coronary angiography: a systematic review and meta-analysis of randomised controlled trials
  1. Alexander J Sharp1,
  2. Nishith Patel2,
  3. Barney C Reeves3,
  4. Gianni D Angelini4 and
  5. Francesca Fiorentino5
  1. 1Addenbrookes Hospital, Cambridge, UK
  2. 2Royal Papworth Hospital, Cambridge, UK
  3. 3Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, UK
  4. 4National Heart & Lung Institute, Imperial College London, London, UK
  5. 5Imperial College Trial Unit and Division of Surgery and Cancer, Imperial College London, St. Mary’s Hospital, London, UK
  1. Correspondence to Dr Alexander J Sharp;{at}


Objective Quantify the efficacy of strategies to prevent contrast-induced acute kidney injury (CI-AKI) in high-risk patients undergoing coronary angiography (CAG) with or without percutaneous coronary intervention (PCI).

Background CI-AKI remains a common problem. The renoprotective efficacy of existing pharmacological agents remains uncertain in high-risk populations.

Methods Systematic review and meta-analysis of randomised controlled trials (RCTs) to compare different strategies versus hydration in patients with chronic kidney disease (CKD) undergoing CAG±PCI. Primary outcome was incident CI-AKI. Fixed-effects meta-analyses estimated ORs, 95% CIs and heterogeneity.

Results Forty-eight RCTs were included. Seven pharmacological strategies were evaluated by multiple RCTs and 10 by one RCT each. These had varying risk of bias; >25% of trials were at high risk of performance bias. Five strategies significantly reduced the odds of CI-AKI: N-acetylcysteine (NAC) (27 trials, 5694 participants; OR=0.77, 95% CI 0.65 to 0.91, p=0.002, I2=36%), ascorbic acid (four trials, 759 participants; OR=0.59, 95% CI 0.39 to 0.89, p=0.01, I2=0%), statin (two trials, 3234 participants; OR=0.59, 95% CI 0.39 to 0.89, p=0.75, I2=0%), trimetazidine (two trials, 214 participants; OR=0.27, 95% CI 0.10 to 0.71, p=0.01, I2=0%) and nicorandil (two trials, 389 participants; OR=0.47, 95% CI 0.23 to 0.94, p=0.03, I2=52%). Theophylline had a similar, but non-significant, effect. A subgroup analysis found that the benefit of NAC was highest in patients requiring a high-contrast dose.

Conclusions Several drugs are renoprotective in patients with CKD undergoing CAG±PCI. The evidence is strongest for NAC. We recommend that NAC should be used when a high dose of contrast is anticipated.

Trial registration number PROSPERO registration CRD42014014704.

Open Science Framework link:

  • Coronary angiography
  • coronary intervention (PCI)
  • contrast media
  • renal disease

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  • Contributors AJS carried out the review under the supervision of FF and NP. NP contributed expertise about kidney dysfunction and coronary disease, advised about aspects of the meta-analysis and drafted the manuscript with FF. BCR conceived the research question, advised about aspects of the meta-analysis and the presentation of the findings of the review. GDA conceived the research question and advised on the clinical interpretation of the data. FF conceived the research question, supervised the conduct of the study, supervised AS, checked the study selection and data extraction and drafted the manuscript with NP. All authors revised the manuscript for important intellectual content and read and approved the final version.

  • Funding BCR’s contribution to this review was funded by the Bristol Biomedical Research Centre (Cardiovascular Theme). GDA holds a British Heart Foundation personal chair (CH/92027/7163). FF’s contribution to this review was funded by the British Heart Foundation.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement FF had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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