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Systematic Review: Sodium Bicarbonate Treatment Regimens for the Prevention of Contrast-Induced Nephropathy

Sophia Zoungas, MD, PhD; Toshiharu Ninomiya, MD, PhD; Rachel Huxley, DPhil; Alan Cass, MD, PhD; Meg Jardine, MD, PhD; Martin Gallagher, MD; Anushka Patel, MD, PhD; Ali Vasheghani-Farahani, MD; Gelareh Sadigh, MD; and Vlado Perkovic, MD, PhD
[+] Article, Author, and Disclosure Information

From the University of Sydney, Sydney, and Monash University, Melbourne, Australia, and Tehran University of Medical Sciences, Tehran, Iran.

Grant Support: Dr. Zoungas was supported by a National Health and Medical Research Council of Australia Health Professional Research Fellowship. Dr. Perkovic was supported by a National Heart Foundation of Australia AstraZeneca research fellowship. Dr. Cass was supported by a National Health and Medical Research Council of Australia Senior Research Fellowship. Drs. Huxley and Patel are supported by National Heart Foundation of Australia Career Development awards.

Potential Conflicts of Interest: None disclosed.

Requests for Single Reprints: Sophia Zoungas, MD, PhD, The George Institute for International Health, University of Sydney, PO Box M201, Missenden Road, Sydney, New South Wales 2050, Australia; e-mail, szoungas@george.org.au.

Current Author Addresses: Drs. Zoungas, Ninomiya, Huxley, Cass, Jardine, Gallagher, Patel, and Perkovic: The George Institute for International Health, University of Sydney, PO Box M201, Missenden Road, Sydney, New South Wales 2050, Australia.

Drs. Vasheghani-Farahani and Sadigh: Department of Cardiology, Tehran Heart Centre, Tehran University of Medical Sciences, Tehran 1411713138, Iran.

Author Contributions: Conception and design: S. Zoungas, T. Ninomiya, A. Cass, V. Perkovic.

Analysis and interpretation of the data: S. Zoungas, T. Ninomiya, R. Huxley, A. Cass, M. Jardine, M. Gallagher, V. Perkovic.

Drafting of the article: S. Zoungas, T. Ninomiya, R. Huxley, M. Gallagher, V. Perkovic.

Critical revision of the article for important intellectual content: T. Ninomiya, R. Huxley, A. Cass, M. Jardine, M. Gallagher, A. Patel, V. Perkovic.

Final approval of the article: S. Zoungas, T. Ninomiya, R. Huxley, A. Cass, M. Jardine, M. Gallagher, A. Patel, A. Vasheghani-Farahani, G. Sadigh, V. Perkovic.

Provision of study materials or patients: A. Vasheghani-Farahani, G. Sadigh.

Statistical expertise: S. Zoungas.

Obtaining of funding: A. Cass.

Administrative, technical, or logistic support: V. Perkovic, T. Ninomiya.

Collection and assembly of data: S. Zoungas, T. Ninomiya.

Ann Intern Med. 2009;151(9):631-638. doi:10.7326/0003-4819-151-9-200911030-00008
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Background: Intravenous sodium bicarbonate has been proposed to reduce the risk for contrast-induced nephropathy (CIN).

Purpose: To determine the effect of sodium bicarbonate on the risk for CIN.

Data Sources: MEDLINE, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from 1950 to December 2008; conference proceedings; and ClinicalTrials.gov, without language restriction.

Study Selection: Randomized, controlled trials of intravenous sodium bicarbonate that prespecified the outcome of CIN as a 25% increase in baseline serum creatinine level or an absolute increase of 44 μmol/L (0.5 mg/dL) after radiocontrast administration.

Data Extraction: Using standardized protocols, 2 reviewers serially abstracted data for each study.

Data Synthesis: 23 published and unpublished trials with information on 3563 patients and 396 CIN events were included. The pooled relative risk was 0.62 (95% CI, 0.45 to 0.86), with evidence of significant heterogeneity across studies (I2 = 49.1%; P = 0.004). Some heterogeneity was due to the difference in the estimates between published and unpublished studies: relative risk, 0.43 (CI, 0.25 to 0.75) versus 0.78 (CI, 0.52 to 1.17), respectively. Meta-regression showed that small, poor-quality studies that assessed outcomes soon after radiocontrast administration were more likely to suggest benefit (P < 0.05 for all). No clear effects of treatment on the risk for dialysis, heart failure, and total mortality were identified.

Limitation: Power to assess clinical end points was limited.

Conclusion: The effectiveness of sodium bicarbonate treatment to prevent CIN in high-risk patients remains uncertain. Earlier reports probably overestimated the magnitude of any benefit, whereas larger, more recent trials have had neutral results. Large multicenter trials are required to clarify whether sodium bicarbonate has value for prevention of CIN before routine use can be recommended.

Primary Funding Source: None.


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Appendix Figure 1.
Literature search and selection.
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Figure 1.
Forest plot of relative risks for contrast-induced nephropathy from 23 studies.

* This study has been published since we did our review.

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Appendix Figure 2.
Funnel plot with pseudo 95% CIs to assess for evidence of publication bias.
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Figure 2.
Subgroup analysis of possible sources of heterogeneity across the published studies.
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Figure 3.
Forest plots of relative risks for adverse clinical events.
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Submit a Comment/Letter
Posted on November 4, 2009
Piero Stratta
Nephrology Transplantation
Conflict of Interest: None Declared

In their comprehensive meta-analysis which included data from all available studies on Contrast-induced Nephropathy (CIN) involving 3563 patients , the authors affirm that CIN is the development of acute renal failure after administration of radiocontrast in the absence of other identifiable causes (1) . However, as some studies evaluated patients having either cardiac catheterization or computed tomography or other arteriography, their systematic examination of potential sources of heterogeneity will be extended to differentiate between patients in whom contrast agents are introduced into the venous or arterial bed, and between patients in whom cardiac catheterization was accessed via the radial or the femoral approach . In fact, it could be a crucial difference among potential risk factors for acute kidney injury when contrast medium is introduced by intra-arterial administration, due to the possible cholesterol crystal embolization occurring after intravascular trauma with angiographic catheters during invasive vascular procedures. In this case , the role of contrast medium in pathophysiology of renal damage might be marginal, if any, due to a possibly undiagnosed atheroembolic renal disease (AERD) masked under a supposed CIN, and a further difference in the degree of AERD might depend on the site of approach ( if radial or femoral). While AERD and CIN share as common setting the need for the use of intravascular contrast medium for diagnostic procedures, pathophysiology of renal damage is completely different: for CIN it is dealing with alteration in renal hemodynamics , rheological properties , and paracrine factors (adenosine, endothelin, reactive oxygen species) or direct cytotoxic effects on renal tubular cells(2,3) , while in the case of AERD the renal parenchyma is mechanically damaged by cholesterol crystals able to trigger inflammatory responses(4,5). Unfortunately, differential diagnosis may be difficult on clinical basis , when local and systemic signs of cholesterol embolism in other organs (gut, skin, upper and lower extremities) such as livedo reticularis , purple toes syndrome, eosinophilia and serum complement consumption are lacking. Many difficulties have been reported in diagnosing AERD, that is labelled as the great masquerader, with an incidence in autopsy studies from 4% in elderly subjects over 65 yr with minimal atherosclerosis to 77% in older patients with severe atherosclerosis, and up to >12% of cases following coronary angioplasty in clinical studies,. Therefore, assessing for heterogeneity in the vascular access will help in differentiating homogeneous clinical entities similar in pathogenesis and , therefore, prevention and treatment.


1) Zoungas S, Ninomiya T, Huxley R, Cass A, Jardine M, Gallagher M, Patel A, Vasheghani-Farahani A, Sadigh G, Perkovic V Systematic review: sodium bicarbonate treatment regimens for the prevention of contrast- induced nephropathy. Ann Intern Med. 2009 ; 151(9):631-8.

2) Solomon R, Dumouchel W. Contrast media and nephropathy: findings from systematic analysis and Food and Drug Administration reports of adverse effects. Invest Radiol. 2006; 41(8):651-60.

3) Brar SS, Hiremath S, Dangas G, Mehran R, Brar SK, Leon MB. Sodium bicarbonate for the prevention of contrast induced-acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2009 ;4(10):1584-92.

4) Baykal C, Buyukbabani N, Aysuna N, Ark E. Clinical outcomes of renal cholesterol crystal embolization. J Nephrol. 1999 ;12:266-9.

5) Khan AM, Jacobs S. Trash feet after coronary angiography. Heart. 2003 ;89: 17.

Conflict of Interest:

None declared

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