Sodium Bicarbonate for the

Prevention of Contrast Induced

Nephropathy:
A Meta-analysis of Published Clinical
Trials
Vijayalakshmi Kunadian1,2, Azfar Zaman1, Weiliang Qiu2

1
Freeman Hospital, Newcastle upon Tyne, United Kingdom;
2
The James Cook University Hospital, Middlesbrough, United Kingdom;
3
Channing Laboratory, Brigham and Women’s Hospital, Boston MA

SCAI Annual Scientific Sessions 2009

Las Vegas
The authors have nothing to disclose
 Background

Contrast induced nephropathy (CIN) is

a serious but rare complication
following contrast based procedures

Sodium bicarbonate has been

demonstrated to prevent CIN through
several mechanisms
 Objective

To perform a meta-analysis of randomized

clinical trials to determine if the
administration of NaHCO3 is superior to
NaCl among patients with chronic renal
failure undergoing catheterization and
interventional procedures in preventing
CIN
 Study Selection

A computerized literature search was

performed on PubMed using the search terms
“contrast nephropathy”, “sodium bicarbonate
(NaHCO3)”, “sodium chloride” (NaCl) and “renal
failure”.

Seven published randomized clinical trials

comparing NaHCO3 vs. placebo or NaCl during
diagnostic and interventional procedures
requiring contrast media administration were
included.
 RCTs Included in the Meta-analysis
Study CKD Procedure Sample Trial design

Brar Yes CA 353 NaCl vs. NaHCO3

Maioli Yes CA, PCI 502 NaCl vs. NaHCO3

Brigouri Yes CA, PA, PCI 326 NaCl+NAC vs. NaCl+NaHCO3

vs. ascorbic acid+NAC

Masuda Yes Em. CA and PCI 59 NaCl vs. NaHCO3

Merten Yes Diagnostic and 119 NaCl vs. NaHCO3

interventional

Ozcan Yes CA, PCI 264 NaCl vs. NaHCO3 vs. NaCl+NAC

Recio- No Urgent or 111 NaCl+NAC vs. NaCl+NaHCO3

Mayoral emergency CA, PCI

CKD-chronic kidney disease, CA-coronary angiography, PCI-Percutaneous coronary intervention, PA-

pulmonary angiography, NAC-N-acetylcysteine
 Outcome Measures
The development of CIN following administration of NaHCO3
and NaCl are provided.

For the purpose of this meta-analysis, CIN was defined as

reported in each of the individual trials.

All studies describe CIN as ≥25% decrease in glomerular

filtration rate (GFR) or an absolute increase of serum creatinine
≥0.5 mg/dl on days 1-5 following the procedure.

Four trials (Brar, Maioli, Masuda and Recio-Mayoral) also report

clinical outcomes on death, dialysis, myocardial infarction and
cerebrovascular events. The occurrence of death, congestive
heart failure and the need for renal replacement therapy
between the two groups were evaluated from these trials.
 Statistical Analysis
DerSimonian and Laird’s random effects model was utilized to
pool the odds ratios (ORs) from individual trials.

Cochran’s Q test was used to evaluate heterogeneity.

Light and Pillemer’s funnel plot and Egger et al.’s regression-

based method were used to assess publication bias.

Duval and Tweedie’s trim-and-fill method was used to adjust

for any observed publication bias.

All analyses were undertaken in statistical software R.

 Baseline Characteristics
Characteristics NaCl (n=772) NaHCO3(n=767) P value

Age 70.12 ± 3.84 69.76 ± 3.73 0.12

Gender 51 (69.59%) 53.52 (69.88%) 0.82
Height 1.68 ± 0.22 1.66 ± 0.22 0.38
Weight 67.01 ± 6.78 67.97 ± 7.06 0.04
BMI 26.35 ± 2.02 26.5 ± 2.41 0.47
Prior MI 23.9 (45.16%) 33.04 (51.16%) 0.65
Prior CHF 14.48 (25.75%) 12.57 (22.09%) 0.54
Prior revasc. 115 (64.6%) 114 (65.1%) 0.92
Diabetes 27.32 (36.19%) 25.98 (35.72%) 0.57
Hypertension 71.74 (71.96%) 76.72 (76.05%) 0.44
Systolic BP 145.27 ± 15.51 143.64 ± 15.51 0.68
Diastolic BP 72.54 ± 7.93 71.66 ± 8.65 0.33
LVEF 51.71 ± 5.8 52.5 ± 5.51 0.55
Data are presented as weighted mean+/-SD and weighted number of events (%)
 Baseline Characteristics
Characteristics NaCl (n=772) NaHCO3(n=767) P value

NAC 84 (47.2%) 80 (45.7%) 0.82

β-blocker 55.5 (76.96%) 57.86 (79.47%) 0.74
ACE inhibitors 39.54 (51.56%) 39.99 (52.81%) 0.89
ARB 21.01 (23.47%) 23.03 (25.76%) 0.19
Statin 39.21 (74.88%) 31.23 (71.28%) 0.7
Diuretic 33.41 (37.57%) 34 (38.31%) 0.75
CCB 19.67 (22.31%) 26.94 (29.29%) 0.51
CA 55.08 (43.05%) 65.44 (51.01%) 0.13
PCI 41.86 (42.31%) 34.59 (38.35%) 0.37
CA, ad hoc PCI 30 (27.02%) 18 (16.67%) 0.07
Contrast vol. 157.39 ± 35.7 157.22 ± 41.4 0.35

Data are presented as weighted mean+/-SD and weighted number of events (%), ARB-angiotensin
receptor blocker, CCB-calcium channel blocker
 Development of CIN:
All Patients
OR 0.33 (0.16, 0.69), P=0.003
Brar 21/158 24/165
Maioli 25/250 29/252
Brigouri 2/108 11/111
Masuda 2/30 10/29
Merten 1/60 8/59
Ozcan 4/88 12/88
Recio-Mayoral 1/56 12/55

Total 750 759

Favours NaHCO3 Favours NaCl

Duval and Tweedie’s trim-and-fill adjustment for publication bias showed there was an
attenuated OR of 0.55 (95% CI 0.27-1.10; P=0.09) among all patients.
 Development of CIN:
Renal Failure Patients
Study NaHCO3 NaCl
OR 0.41 (0.20, 0.82), P=0.01
Brar 21/158 24/165
Maioli 25/250 29/252
Brigouri 2/108 11/111
Masuda 2/30 10/29
Merten 1/60 8/59
Ozcan 4/88 12/88

Total 694 704

Favours NaHCO3 Favours NaCl

Duval and Tweedie’s trim-and-fill adjustment for publication bias showed there was
an attenuated odds ratio of 0.70 (95% CI 0.35-1.43; P=0.33).
 Development of CIN:
Among Patients Who Received NAC
Study NaHCO3 NaCl
Brigouri 2/108 11/111
OR 0.12 (0.04, 0.42),

Recio-Mayoral 1/56 12/55 P=0.0008

Total 164 166

Favours NaHCO3 Favours NaCl

NAC-N-acetylcysteine
Need for Renal Replacement
Therapy
Study NaHCO3 NaCl
OR 0.56 (0.22, 1.41), P=0.22
Brar 2/175 4/178
Maioli 1/250 1/252
Brigouri 1/111 1/111
Masuda 1/30 3/29
Merten 0/60 0/59
Ozcan 1/88 1/88
Recio-Mayoral 1/56 3/55

Total 770.5 772.5

Favours NaHCO3 Favours NaCl

 Clinical Endpoint: Death
Study NaHCO3 NaCl
Brar 4/175 7/178
OR 0.60 (0.26, 1.41),
Maioli 4/250 3/252 P=0.24
Masuda 0/30 2/29
Recio-Mayoral 1/56 4/55

Total 511 514

Favours NaHCO3 Favours NaCl

Clinical Endpoint: Heart Failure
Study NaHCO3 NaCl
Masuda 11/30 11/29
OR 0.85 (0.32, 2.24),
P=0.74
Recio-Mayoral 1/56 2/55

Total 86 84

Favours NaHCO3 Favours NaCl

 Limitations
The results observed here may not be
applicable to all patients in clinical practice.

The present study remains subject to the

inherent caveats of a meta-analysis including
publication-bias.

Patient level data was not available in this

study.

The dose of NaHCO3 varied across the trials.

 Conclusions

The present meta-analysis demonstrates that

based on currently available randomized trials,
the administration of NaHCO3 is superior to
administration of NaCl alone in the prevention
of CIN among patients with moderate to severe
CKD undergoing diagnostic and interventional
procedures requiring contrast media.
 Conclusions
The use of NaHCO3 however, did not result in significant
benefit in terms of reductions in death, heart failure and
the requirement for renal replacement therapy.

The results of this study should be considered in the

context of publication bias inherent to meta-analysis.

Adequately powered studies are required to determine

the beneficial effect of NaHCO3 in preventing CIN and
improving short-term and long-term clinical outcomes
among patients who undergo coronary diagnostic and
interventional procedures requiring contrast media.