Abstract
Contrast-induced nephropathy (CIN) is a form of acute kidney injury and a significant source of morbidity and mortality. We defined CIN as an increase in serum creatinine (SCr) of 25% or more within 48 hours of receiving contrast. We retrospectively compared sodium bicarbonate with normal saline for prevention of CIN. One hundred and eighty-seven patients exposed to contrast during cardiac angiography, treated prophylactically either with sodium bicarbonate (n = 89) or with normal saline (n = 98), were studied. Baseline characteristics of both groups were similar in terms of age, amount of contrast, presence of diabetes mellitus, and use of furosemide and angiotensin-converting enzyme inhibitor. Patients in bicarbonate group had more severe renal disease with higher baseline SCr (1.58 ± 0.5 mg/dL vs. 1.28 ± 0.3 mg/dL, p = 0.001) and lower estimated glomerular filtration rate (eGFR, 51.06 ± 14.0 mL/min vs. 62.3±13.5 mL/min, p = 0.001) compared to the normal saline group. After the contrast exposure, there was significant drop in eGFR (6.4%) and increase in SCr (11.3%) in the normal saline group and no significant change in the bicarbonate group. Three patients (3.4%) in the bicarbonate group as opposed to 14 patients (14.3%) in the normal saline group developed CIN (p = 0.011). Two patients in the normal saline group and none in the bicarbonate group needed dialysis. There was no significant difference in serum creatinine at three-month follow-up in either group. The above findings suggest that hydration with intravenous sodium bicarbonate is more effective than normal saline in preventing contrast-induced nephropathy.
INTRODUCTION
Contrast-induced nephropathy (CIN) is a leading cause of acute kidney injury and is associated with increased morbidity, mortality, hospital stay, and progression to end stage renal disease, mainly in patients with pre-existing kidney disease.Citation[1],Citation[2] There has been greater utilization of contrast for coronary angiograms and computed tomograms in the recent years. Most trials have defined CIN as an increase in serum creatinine (SCr) by 25% or more within 48 hours of receiving contrast medium (CM).Citation[1],Citation[3] Risk of contrast-mediated renal failure varies from 1 to 50%, depending on underlying kidney disease.Citation[4–6] The likely mechanism of contrast media injury involves tubular damage by induction of renal ischemia and oxygen free radical production.Citation[7],Citation[8] Dehydration increases the concentration of the dye delivered to the tubules; hence, intravenous volume expansion with a saline and minimizing the amount of contrast agent are used for prevention of CIN. Intravenous sodium bicarbonate has a urinary alkalinizing effect that may reduce the generation of reactive oxygen species by CM and protect the kidneys from the cytotoxic radicals. Acetazolamide has been shown to decrease the incidence of CIN in animal models by inhibiting bicarbonate reabsorption and increasing urine pH.Citation[9]
The present study was undertaken to compare the effects of sodium bicarbonate with normal saline for prophylaxis of CIN in high-risk patients who underwent cardiac catheterization.
METHODS
Study Sample
We performed a retrospective chart review of patients that underwent non-emergent coronary angiogram at the Veterans Affair Hospital, from January 2003 to December 2007. We obtained patient information from the electronic database located in the VA network. Selection criteria included patients with age ≥ 18 years, baseline serum creatinine >1.0mg/dL (before hydration), and availability of serum creatinine values at days 1–3 and around three months post-procedure. Patients with shock, hypotension, end stage renal disease, multiple myeloma, allergy to contrast media, use of NSAIDS, acetylcysteine, and prior exposure to contrast within five days were excluded from the study.
Iopromide (300 mgI/ml), a non-ionic, low-osmolar contrast agent, was used in all patients. Patients exposed to CM during cardiac angiography were divided into two groups, one that was treated prophylactically either with intravenous sodium bicarbonate (approximately 3 mL/kg/hour of sodium bicarbonate for 1 h before contrast administration, followed by an infusion of 1 mL/ kg/hour during and after the procedure for 6 hours) or with normal saline (around 1mL/kg/hour for 12 hours prior and after the procedure).
Study Data
Serum creatinine values before angiogram, on days 1–3, and at three months were recorded. The estimated glomerular filtration rate (eGFR) was calculated using Modification of Diet in Renal Disease Study (MDRD-Levey) formula.Citation[10] The primary end point was development of CIN, defined as a 25% or higher increase in serum creatinine concentration from the baseline value within 48 hours after administration of the contrast media. Secondary end points were acute renal failure requiring dialysis, renal recovery at three months post-exposure, and change in serum bicarbonate, potassium, and calcium levels after hydration.
Statistics
Continuous variables are represented as mean+/-SD, and differences between means were compared using student's t test. All categorical variables were reported as absolute values and percentages, and test for significance was done by using chi-square test. Linear regression was used to compare changes in creatinine between the treatment groups while taking considerations of baseline values. Multiple logistic analyses were conducted to assess the odd ratios for contrast nephropathy by bicarbonate treatment while controlling for possible confounding factors including age, diabetes mellitus (DM), ACE inhibitor/angiotensin receptor blocker (ACEi/ARB), furosemide, and dye load. All statistical tests were two-tailed, and statistical significance was considered at p < 0.05. Statistical analyses were carried out using SPSS 10.0 (SPSS Inc, Chicago, Illinois, USA).
RESULTS
We reviewed charts of 900 patients; of these, 187 patients were treated prophylactically either with intravenous sodium bicarbonate (n = 89) or with normal saline (n = 98). The two groups were similar in terms of age, presence of diabetes mellitus, use of furosemide, or use of angiotensin converting enzyme inhibitor/angiotensin receptor blockers at baseline (see ). All participants were men. Patients in bicarbonate group had more severe renal disease with higher baseline SCr (1.58 ± 0.5 mg/dL vs. 1.28 ± 0.3 mg/dL, p = 0.001) and lower eGFR (51.06 ± 14.0 mL/min vs. 62.3 ± 13.5 mL/min, p = 0.001) compared to the normal saline group. The amount of CM (193.9 ± 83.03 vs. 204.1 ± 102.7, p = 0.452) was not significantly different. There was a non-significant trend toward the dye load, calculated by dividing the amount of dye by eGFR, to be higher in the bicarbonate group (4.01 ± 1.7 vs. 3.5 ± 2.16, p = 0.063). Highest baseline creatinine in bicarbonate group was 3.7 mg/dL and in normal saline group was 2.8 mg/dL. After adjusting for baseline creatinine using linear regression model, the change in creatinine was significant (p = 0.022).
Table 1 Baseline characteristics
Post-Procedure
Incidence of CIN
After the contrast administration, there was significant decrease in eGFR (6.4%) and increase in SCr (11.3%) in the normal saline group, while no significant change was noted in the bicarbonate group (see ). Only three patients (3.4%) in the bicarbonate group as opposed to 14 patients (14.3%) in the normal saline group developed CIN (p = 0.011). Logistic regression analysis revealed a significant protective effect of bicarbonate against contrast mediated acute kidney injury (OR, 0.29; 95% CI 0.58–0.75; p = 0.17; see ).
Table 2 Renal function pre- and post-angiogram
Table 3 Results from logistic regression showing risk for contrast nephropathy by treatment (normal saline is the reference group)
Dialysis
Two patients in the normal saline group but none in the bicarbonate group needed dialysis (p = 0.5). One patient recovered and the other one declined to undergo hemodialysis and died (see ).
Table 4 Characteristics of the two patients in the normal saline group that required hemodialysis
Kidney Function at Three Months
The mean creatinine was higher in the bicarbonate group at baseline and continued to be higher at three months. However, there was no significant difference in change in SCr at three months compared to the baseline values in either group (see ).
Electrolytes Post-Procedure
Serum bicarbonate increased by 2.13 ± 2.3 mMol/L in the bicarbonate group, and decreased by 1.10 ± 2.02 mMol/L in saline group (p = 0.001; see ). Serum potassium decreased in the bicarbonate group by 0.14 ± 0.4 mMol/L and the saline group by 0.02 ± 0.35 mMol/L (p = 0.019). No significant change in serum calcium (−0.01 ± 0.3 mg/dL vs. −0.05 ± 0.3 mg/dL, p = 0.334) was recorded; however, there were only 38 patients in the bicarbonate group and 41 patients in normal saline group who had pre- and post-procedure calcium levels available. No patient had adverse events related to change in electrolyte levels.
Table 5 Electrolyte changes post-hydration
DISCUSSION
There was a lower incidence of CIN in the bicarbonate group compared to the normal saline group, even though the bicarbonate group had higher degree of kidney insufficiency at baseline. There was a significant increase in serum creatinine post-procedure in the normal saline group, but at three-month follow up, serum creatinine was not different from the baseline in either group. Greater incidence of dialysis was seen in the normal saline group. The published incidence of dialysis in CIN varies widely, between 0.4% and 3%. Our sample size is not enough to report significant difference in need for dialysis between the normal saline and the bicarbonate groups.Citation[11]
Our study suggests that hydration with intravenous sodium bicarbonate is more effective than normal saline in preventing contrast-induced nephropathy in high-risk elderly male patients who undergo cardiac catheterization. This is a retrospective single-center trial with a long follow-up measurements of kidney function. Likewise, as opposed to other reports, Mucomyst was not employed in either group in the present study. This has been considered as a confounding variable in a recent study.Citation[1–2] Furthermore, the amount of dye used in our study was higher than what had been used in previous studies.Citation[13–16] Our patients were elderly veterans: all had cardiac catheterization, and many of them needed intervention.
Several studies evaluated the effects of sodium bicarbonate for prevention of CIN. The first one by Merten et al.Citation[13] studied 119 patients and reported decreased incidence of CIN with sodium bicarbonate (1.7% vs. 13%). The benefit was larger in patients who underwent cardiac catheterization (1.7% vs. 15%). However, this was a small study and was terminated early. A REMEDIAL trialCitation[14] that involved 326 patients reported lower incidence of CIN with the use of bicarbonate and Mucomyst vs. normal saline and Mucomyst. The RENO trialCitation[17] included patients who underwent emergency cardiac angiogram and reported a lower incidence of CIN in those who received sodium bicarbonate and Mucomyst compared to those receiving normal saline and Mucomyst. However, the normal saline group received hydration only after but not before the procedure.
Increased incidence of CIN was reported with the use of bicarbonate by From et al.,Citation[15] who retrospectively looked at 7797 patients of which 268 received bicarbonate only and had higher incidence of CIN (35% vs. 11%). However, only 16% received bicarbonate according to Merten's protocol; the remaining patients were given bicarbonate within 48 hrs after exposure. In contrast to this study, wherein only 10% of the patients had cardiac catheterization and the rest received contrast agents intravenously for noncoronary and noncardiac CT imaging, all of our patients received contrast agents intra-arterially during cardiac catheterization.
Our study is an observational study with conventional patients groups, so there are differences in the characteristics of the patients in different treatment groups. The strength of this study is that the protocol of hydration is closely followed, and complete information available in the VA network helps in collecting data rigorously. The bicarbonate group was at a higher baseline creatinine and higher risk of CIN; the providers could have taken extra caution while performing angiograms or when implementing hydration protocol. The amount of hydration was higher in the saline group; this could have lead to false decrease in serum creatinine secondary to dilution, which would support the role of bicarbonate more.
In conclusion, our study conducted in high risk elderly male veterans who underwent cardiac catheterization and showed a noteworthy decrease in the incidence of CIN with bicarbonate use. As to above, evidence regarding use of bicarbonate for prevention of CIN is conflicting. Future research should involve well-designed randomized prospective trials examining different preventive strategies in high-risk patients and should be well-powered to detect differences in mortality and the need for dialysis.
DECLARATION OF INTEREST
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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