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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2016  |  Volume : 27  |  Issue : 3  |  Page : 519-525
Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy


1 Department of Nephrology, Theodor Bilharz Research Institute, Cairo, Egypt
2 Department of Cardiology, Faculty of Medicine, Kasr Al Ainy Cairo University, Giza, Egypt

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Date of Web Publication13-May-2016
 

   Abstract 

Contrast-induced nephropathy (CIN) is one of the important complications of radiographic procedures, especially in patients with chronic kidney disease. It is also one of the common causes of acute kidney injury. The pathogenesis is postulated to be the effect of oxygen- free radicals and hyperosmolar stress on the renal medulla. It is reported that the production of superoxide is most active at acid environment. K/Na citrate is well known as a urine alkalini- zation medium, and this has been evaluated earlier with standard hydration for reduction of CIN and was stated to be efficient. We aimed to determine the efficacy of Na/K citrate in reducing the frequency of CIN in comparison to sodium bicarbonate in patients after coronary angiography. Two hundred and ten patients with renal dysfunction [estimated glomerular filtration rate (eGFR), 60 mL/min/1.73 m2or less] who underwent elective or emergency coronary angiography (CAG) with/without percutaneous coronary intervention (PCI) at our institution were enrolled into the study. The patients were randomized into two groups, Group 1-Taking Na/K citrate and Group 2-Taking sodium bicarbonate. Radiographic contrast agent iohexol was used. Change in creatinine, percent change in creatinine, percent change in eGFR, change in serum potassium, and urine pH were all compared between the two groups. There was no significant difference for prevention of CIN when comparing the Na/K citrate with sodium bicarbonate solution in patients exposed to CAG with or without PCI. Mean absolute change in eGFR after 48 h after administration of contrast between sodium bicarbonate group and Na/K citrate group was −0.60 ± 1.58 versus −0.71 ± 1.38. Serum potassium decreased postprocedure in the sodium bicarbonate group than in the citrate group (3.90 ± 0.33 vs. 4.14 ± 0.39). Both agents are equally effective in reducing the incidence of CIN, but the citrate would possibly be a safer option for patients at risk of hypokalemia.

How to cite this article:
Abouzeid SM, ElHossary HE. Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy . Saudi J Kidney Dis Transpl 2016;27:519-25

How to cite this URL:
Abouzeid SM, ElHossary HE. Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy . Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Sep 20];27:519-25. Available from: http://www.sjkdt.org/text.asp?2016/27/3/519/182386

   Introduction Top


Contrast-induced nephropathy (CIN) is one of the important complications of radiographic procedures, especially in patients with chronic kidney disease. It is also one of the common causes of acute kidney injury.[1],[2],[3],[4],[5]Its incidence varies and depends on the type and amount of the contrast medium used and the characte- ristics of the patients receiving contrast. The frequency of CIN ranges from 2% to 50% in the high-risk patients.[6],[7],[8]

Several theories of the pathogenesis of CIN exist, one of them postulating the effect of oxygen-free radicals and hyperosmolar stress on the renal medulla.[9],[10]It was reported that the production of superoxide is most active at acid environment,[11]and urine alkalization by sodium bicarbonate is thought to result in re- duction of CIN.[11],[12],[13],[14],[15]

K/Na citrate is well known as a urine alkali- nization medium. It is mainly administered to patients with kidney stones (cystine, uric acid, and calcium stones), which require alkalini- zation.[16],[17],[18]Na/K citrate with standard hydra- tion was evaluated for reduction of CIN earlier and was stated to be efficient.[19]

Taking into consideration that alkalinization of urine can be used to prevent CIN, we aimed to determine the efficacy of Na/K citrate in reducing the frequency of contrast nephro- pathy in comparison to sodium bicarbonate in patients after coronary angiography (CAG).


   Subjects and Methods Top


Study population

The protocol of this study was approved by the Ethics Committee, and written informed consent was obtained from all patients. The study complies with the Declaration of Helsinki. All adult (>18 years) patients scheduled for CAG were screened for inclusion and exclu- sion criteria.

Between November 2013 and November 2014, a total of 480 patients were screened, and 310 were considered eligible for the trial. Consecutive patients with renal dysfunction [estimated glomerular filtration rate (eGFR), 60 mL/min/1.73 m2or less] who underwent elective or emergent CAG with/without percu- taneous coronary intervention (PCI) at our ins- titution were enrolled. The eGFR was calcu- lated using the Modification of diet in renal disease (MDRD) formula: GFR = 175 × serum Cr−1.154× age−0.203× 1.212 (if patient is black) × 0.742 (if female).[20]Patients were excluded for any of the following reasons: end-stage renal insufficiency (eGFR <15 mL/min), acute renal insufficiency, a history of reaction to contrast media, use of potentially nephrotoxic medicines (48 h before and 24 h after the pro- cedure), pulmonary edema, multiple myeloma, exposure to contrast media within seven days before the procedure, pregnancy, noncom- pliance of the patient, and use of drugs such as N-acetylcysteine, dopamine, fenoldopam, and mannitol before CAG.

After further 100 exclusions based on these, 210 patients were enrolled as the final study population, and they were randomly assigned into two groups:

  1. Group 1: group taking Na/K citrate
  2. Group 2: group taking sodium Bicarbonate.
Patients were randomized either to the Na/K citrate group or to the sodium bicarbonate group using sealed and opaque envelopes. The sequence and the envelopes were locked in the data-coordinating center, and the investigator opened the envelope only in the moment of patient's admission to the study.

Protocol

All patients were hydrated with intravenous (i.v.) normal saline at 1 mL/kg/h for 12 h before exposure to the contrast and 12 h after coronary angiography. The rate of infusion was reduced in patients, who developed signs of pulmonary congestion, we determined urine pH an hour before CAG for all patients.

Group 1 received the Na/K citrate solution (Uralyt U, Madaus granulat, Germany) at a dose of 5 g of granules diluted in 200 mL of water 12, 6, and 1 h before procedure followed by another two doses after 2 and 8 h postpro- cedure.

Group 2 received 1 mL/kg of sodium bicar- bonate solution (150 mEq/L) for 8 h before procedure continued until 6 h postprocedure.

In the study, urine pH was measured imme- diately after taking the samples (using the automatic pH indicator). We used nonionic radiographic contrast agent iohexol (640 mOsm/L, 647 mg of iohexol/mL). The amount of the contrast medium administered during CAG was measured for each patient (nearest 5 mL).

Demographic data, current medication, and medical history were recorded at baseline. Serum creatinine, eGFR, and serum potassium were measured before initiating the preproce- dural hydration. Urine samples were obtained to analyze pH of the urine 1 h before proce- dure. Two days after coronary angiography, serum creatinine, eGFR, and serum potassium were analyzed again. We again calculated eGFR according to the MDRD formula.[20]Change in creatinine, percent change in crea- tinine, percent change in eGFR, change in serum potassium, and urine pH were all com- pared between the two groups. Side effects of high-dose sodium bicarbonate such as conges- tive heart failure, respiratory disorder, and low potassium, were carefully evaluated during the study.

CIN was defined as an increase of more than absolute 0.5 mg/dL and/or relative 25% in serum creatinine after 48 h.


   Results Top


Out of the 480 patients who were screened, 310 were considered eligible for the trial. After further exclusions of 100 cases based on other exclusion criteria, 210 patients were randomly assigned to treatment either with bicarbonate solution (105 patients) or with Na/K citrate (105 patients). Thus, 210 patients were the final study population.

No side effects of sodium bicarbonate or i.v. normal saline infusions were observed, and discontinuation of protocol dose of infusion was not necessary in any patient.

[Table 1] represents baseline clinical characte- ristics for two groups. There were no signi- ficant differences between the two groups in age, gender, body mass index, smoking, dia- betes mellitus, hypertension, percutaneous co- ronary intervention, and volume of contrast administered.
Table 1. Baseline characteristics of the two studied groups

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[Table 2] represents preprocedural and renal outcome values. There was no statistical diffe- rence in baseline serum creatinine, baseline eGFR by MDRD, and baseline serum potas- sium. Although eGFR after 48 h and serum creatinine after 48 h were slightly higher in the citrate group, there was no statistical diffe- rence regarding those parameters in the two studied groups. Serum potassium has clearly decreased postprocedure in the sodium bicar- bonate group than in the citrate group (3.90 ± 0.33 vs. 4.14 ± 0.39) showing a statistical difference in absolute and relative change. [Table 3] represents mean urine pH prepro- cedural and there was no statistical difference between two studied groups and apparently there was no statistical significance whether urine pH was above or below 6.
Table 2. Preprocedural and renal outcome values

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Table 3. Urine pH preprocedural

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[Table 4] represents the correlation between the urine pH with serum creatinine and eGFR in the citrate group with a significant corre- lation between urine pH and eGFR after 48 h.
Table 4. Correlation between different studied parameters in citrate group

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In addition, a highly significant correlation between contrast volume with serum crea- tinine and eGFR in the citrate group was also noticed. However, there was no correlation between serum potassium with serum crea- tinine and eGFR in the same group.

[Table 5] represents the correlation between the Urine pH with serum creatinine and eGFR in the sodium bicarbonate group with no corre- lation between urine pH and eGFR after 48 h, also a highly significant correlation between contrast volume with serum creatinine and eGFR in the sodium bicarbonate group was noticed. There was no correlation between serum potassium with serum creatinine and eGFR in the same group.
Table 5. Correlation between different studied parameters in sodium bicarbonate group

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   Discussion Top


The mechanism of CIN remains still unknown, but previous studies indicated that oxidative stress by the reactive oxygen species in the renal medulla plays a role in CIN. The super- oxide generated by the Haber-Weiss reaction accounts for free radical production in the renal medulla. This reaction is most active in an acid (pKa = 4.9) environment. Sodium bicarbonate might protect from oxidant injury by increasing medullary pH, and slowing free radical production.[11],[21],[22]

The most important risk factors for the deve- lopment of CIN are chronic kidney insuffi- ciency and diabetic nephropathy.[23],[24]In the general population, the risk for CIN is <2% but can increase to 38% in patients with diabetes mellitus who have serum creatinine concentrations above 1.5 mg/dL and to 50% in patients with diabetes and serum creatinine concentrations of 4-5 mg/dL.[23],[24]

]
Other risk factors associated with CIN deve- lopment include age older than 70 years, vo- lume depletion, anemia, heart failure, hypoten- sion, concomitant use of nephrotoxic drugs such as nonsteroidal anti-inflammatory drugs, diuretics, aminoglycosides, amphotericin B, angiotensin-converting enzyme inhibitors, high dose of contrast, and type of contrast medium used.[23],[24],[25],[26]

The current study was designed to evaluate the efficacy of Na/K citrate in reducing the fre- quency of contrast nephropathy in comparison to sodium bicarbonate in patients after CAG. In the current study, the most important fin- ding was the absence of a significant difference for the prevention of CIN when comparing the Na/K citrate with sodium bicarbonate solution in patients exposed to coronary angiography with or without PCI.

It is supposed that the administration of so- dium bicarbonate is successful in the preven- tion of contrast nephropathy as a result of urine alkalinization.[27]Numerous studies reported the efficacy of sodium bicarbonate in the preven- tion of CIN,[11],[13],[14],[15]but on the other hand, some studies failed to document a significant effect.[28]The results of the current study showed that there was no statistical difference in the absolute or relative change in eGFR after 48 h after administration of contrast between the sodium bicarbonate group and the Na/K Citrate group, mean absolute change was −0.60 ± 1.58 versus −0.71 ± 1.38 denoting that they both almost have same preventive efficacy.

Mean urinary pH was 5.99 ± 0.17 in citrate group versus 5.95 ± 0.25 in the bicarbonate group with no statistical difference highlighting the fact that both the citrate and sodium bicar- bonate has almost the same alkalinizing effi- cacy, with no proven extra benefit for patients with pH more than 6.

As with most reported studies, our study showed that there is a highly significant correlation between contrast volume and the creatinine 48 h postprocedure and eGFR 48 h postprocedure in both groups, the citrate and the sodium bicarbonate group, the higher the contrast volume, the greater the risk for CIN after 48 h.

Our study also showed that serum potassium has clearly decreased postprocedure in the sodium bicarbonate group than in the citrate group 3.90 ± 0.33 versus 4.14 ± 0.39 showing a statistical difference in absolute and relative change, giving an advantage for citrate over sodium bicarbonate.

Certainly, satisfactory hydration and volume of administered contrast medium remain the foundation of CIN prevention. To add on the results of our study document that oral admi- nistration of citrates is an efficient strategy to prevent CIN.

Conclusions

Our study demonstrates that both agents are equally effective in reducing the incidence of CIN, but the citrate would possibly be the safer option for the patients at risk of hypo- kalemia and looking at the results, it should be used in all patients with K level <4 mmol/L. Furthermore, citrate would be safer for patients at risk of fluid overload. Equally, sodium bicarbonate would be the safer option for patient who are volume depleted or those with high serum K levels.

Conflict of interest: None.



 
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Correspondence Address:
Sameh Mohamed Abouzeid
Department of Nephrology, Theodor Bilharz Research Institute, Cairo
Egypt
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DOI: 10.4103/1319-2442.182386

PMID: 27215244

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