|Year : 2016 | Volume
| Issue : 3 | Page : 519-525
|Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy
Sameh Mohamed Abouzeid1, Hossam E ElHossary2
1 Department of Nephrology, Theodor Bilharz Research Institute, Cairo, Egypt
2 Department of Cardiology, Faculty of Medicine, Kasr Al Ainy Cairo University, Giza, Egypt
Click here for correspondence address and email
|Date of Web Publication||13-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|| |
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.,,,,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.,,
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.,It was reported that the production of superoxide is most active at acid environment,and urine alkalization by sodium bicarbonate is thought to result in re- duction of CIN.,,,,
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.,,Na/K citrate with standard hydra- tion was evaluated for reduction of CIN earlier and was stated to be efficient.
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|| |
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).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:
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.
- Group 1: group taking Na/K citrate
- Group 2: group taking sodium Bicarbonate.
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.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|| |
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 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 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|
Click here to view
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|
Click here to view
| Discussion|| |
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.,,
The most important risk factors for the deve- lopment of CIN are chronic kidney insuffi- ciency and diabetic nephropathy.,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.,
]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.,,,
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.Numerous studies reported the efficacy of sodium bicarbonate in the preven- tion of CIN,,,,but on the other hand, some studies failed to document a significant effect.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.
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.
| References|| |
Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal insuffi- ciency: A prospective study. Am J Med 1983; 74:243-8.
McCullough PA, Wolyn R, Rocher LL, Levin RN, O'Neill WW. Acute renal failure after coronary intervention: Incidence, risk factors, and relationship to mortality. Am J Med 1997; 103:368-75.
Best PJ, Lennon R, Ting HH, Bell MR, Rihal CS, Holmes DR, et al. The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interven- tions. J Am Coll Cardiol 2002;39:1113-9.
Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, et al. Incidence and prog- nostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002;105:2259-64.
Abe M, Kimura T, Morimoto T, Furukawa Y, Kita T. Incidence of and risk factors for contrast- induced nephropathy after cardiac catheteri- zation in Japanese patients. Circ J 2009;73: 1518-22.
Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: Development and initial validation. J Am Coll Cardiol 2004;44:1393-9.
Nikolsky E, Mehran R, Turcot D, Aymong ED, Mintz GS, Lasic Z, et al. Impact of chronic kidney disease on prognosis of patients with diabetes mellitus treated with percuta- neous coronary intervention. Am J Cardiol 2004;94:300-5.
Nikolsky E, Aymong ED, Dangas G, Mehran R. Radiocontrast nephropathy: Identifying the high-risk patient and the implications of exacerbating renal function. Rev Cardiovasc Med 2003;4 Suppl 1:S7-14.
Katholi RE, Woods WT Jr., Taylor GJ, Deitrick CL, Womack KA, Katholi CR, et al. Oxygen free radicals and contrast nephropathy. Am J Kidney Dis 1998;32:64-71.
Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ; Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media Study Investigators. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-9.
Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, et al. Preven- tion of contrast-induced nephropathy with sodium bicarbonate: A randomized controlled trial. JAMA 2004;291:2328-34.
Recio-Mayoral A, Chaparro M, Prado B, Cózar R, Méndez I, Banerjee D, et al. The reno-pro- tective effect of hydration with sodium bicarbonate plus N-acetylcysteine in patients undergoing emergency percutaneous coronary intervention: The RENO Study. J Am Coll Cardiol 2007;49:1283-8.
Briguori C, Airoldi F, D'Andrea D, Bonizzoni E, Morici N, Focaccio A, et al. Renal Insuffi- ciency Following Contrast Media Administra- tion Trial (REMEDIAL): A randomized com- parison of 3 preventive strategies. Circulation 2007;115:1211-7.
Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O, Baris N, et al. Sodium bicar- bonate, N-acetylcysteine, and saline for pre- vention of radiocontrast-induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures. A single- center prospective controlled trial. Am Heart J 2007;154:539-44.
Masuda M, Yamada T, Mine T, Morita T, Tamaki S, Tsukamoto Y, et al. Comparison of usefulness of sodium bicarbonate versus so- dium chloride to prevent contrast-induced ne- phropathy in patients undergoing an emergent coronary procedure. Am J Cardiol 2007;100: 781-6.
Fjellstedt E, Denneberg T, Jeppsson JO, Tiselius HG. A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalini- zation of urine in homozygous cystinuria. Urol Res 2001;29:295-302.
Cicerello E, Merlo F, Maccatrozzo L. Urinary alkalization for the treatment of uric acid nephrolithiasis. Arch Ital Urol Androl 2010;82: 145-8.
Caudarella R, Vescini F. Urinary citrate and renal stone disease: The preventive role of alkali citrate treatment. Arch Ital Urol Androl 2009;81:182-7.
Markota D, Markota I, Starcevic B, Tomic M, Prskalo Z, Brizic I. Prevention of contrast- induced nephropathy with Na/K citrate. Eur Heart J 2013;34:2362-7.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-12. Erratum in: Ann Intern Med 2011;155:408.
Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: An overview. Methods Enzymol 1990;186:1-85.
Bakris GL, Lass N, Gaber AO, Jones JD, Burnett JC Jr. Radiocontrast medium-induced declines in renal function: A role for oxygen free radicals. Am J Physiol 1990;258(1 Pt 2):F115-20.
Briguori C, Tavano D, Colombo A. Contrast agent - Associated nephrotoxicity. Prog Cardiovasc Dis 2003;45:493-503.
Andrew E, Berg KJ. Nephrotoxic effects of X- ray contrast media. J Toxicol Clin Toxicol 2004; 42:325-32.
Barrett BJ, Parfrey PS. Clinical practice. Preventing nephropathy induced by contrast medium. N Engl J Med 2006;354:379-86.
Mehran R, Nikolsky E. Contrast-induced nephro- pathy: Definition, epidemiology, and patients at risk. Kidney Int Suppl 2006; (100):S11-5.
Meier P, Ko DT, Tamura A, Tamhane U, Gurm HS. Sodium bicarbonate-based hydra- tion prevents contrast-induced nephropathy: A meta-analysis. BMC Med 2009;7:23.
Vasheghani-Farahani A, Sadigh G, Kassaian SE, Khatami SM, Fotouhi A, Razavi SA, et al. Sodium bicarbonate plus isotonic saline versus saline for prevention of contrast-induced nephropathy in patients undergoing coronary angiography: A randomized controlled trial. Am J Kidney Dis 2009;54:610-8.
Sameh Mohamed Abouzeid
Department of Nephrology, Theodor Bilharz Research Institute, Cairo
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
| Article Access Statistics|
| Viewed||2462 |
| Printed||23 |
| Emailed||0 |
| PDF Downloaded||653 |
| Comments ||[Add] |