International Urology and Nephrology

, Volume 41, Issue 3, pp 617–627 | Cite as

Sodium bicarbonate for the prevention of contrast-induced nephropathy: a meta-analysis of 17 randomized trials

  • Mehmet Kanbay
  • Adrian Covic
  • Steven G. Coca
  • Faruk Turgut
  • Ali Akcay
  • Chirag R. Parikh
Nephrology - Orginal Article



Contrast-induced nephropathy (CIN) is a common cause of acute kidney injury. Several preventive therapies for this injury have been tested; however, there is still no consensus on the optimal protocol.


We performed a systematic search of the National Library of Medicine and the Cochrane Library databases from January 1985 to November 2008 to identify randomized controlled studies examining sodium bicarbonate as a preventive measure for CIN in humans. We also reviewed conference abstracts from cardiology nephrology and radiology meetings from 2004 to 2008. A change in serum creatinine levels defined by an absolute (≥0.5 mg/dl) or percentage (≥25%) increase in the serum creatinine level is defined as CIN. The primary outcome measure was the incidence of CIN, and the secondary outcome measures were: change in serum creatinine from baseline, requirement for renal replacement therapy and death.


Seventeen randomized controlled trials have investigated the role of sodium bicarbonate for prophylaxis of CIN. The overall incidence of CIN was 11.3%. Using the results from all 17 studies that compared bicarbonate versus saline, the pooled relative risk of developing CIN was 0.54 (95% CI, 0.36–0.83) in the intervention arm, indicating a significant benefit from sodium bicarbonate. The pooled relative risk of CIN was 0.57 (95% CI, 0.35–0.95) when we analyzed for the studies that compared the effects sodium bicarbonate to NAC on development of CIN. There was no difference in the rates of requirement for renal replacement therapy and death.


The use of sodium bicarbonate appears to reduce the incidence of CIN when compared to other preventive strategies for CIN without a significant difference in the requirement of renal replacement therapy and mortality. There are study heterogeneity and publication biases. Further adequately powered randomized controlled studies are needed to determine whether sodium bicarbonate will reduce the clinically meaningful outcomes (e.g., need for dialysis or death) and optimal hydration strategy in high-risk patients.


Acute renal failure Contrast-induced nephropathy Sodium bicarbonate 



No financial support was obtained from any institution or company except for logistic support from the authors’ affiliation departments.


  1. 1.
    Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11:177–182PubMedGoogle Scholar
  2. 2.
    Weisbord SD, Chen H, Stone RA, Kip KE, Fine MJ, Saul MI, Palevsky PM (2006) Associations of increases in serum creatinine with mortality and length of hospital stay after coronary angiography. Am Soc Nephrol 17(10):2871–2877. doi: 10.1681/ASN.2006030301 CrossRefGoogle Scholar
  3. 3.
    Rudnick M, Feldman H (2008) Contrast-induced nephropathy: what are the true clinical consequences? Clin J Am Soc Nephrol 3(1):263–272. doi: 10.2215/CJN.03690907 PubMedCrossRefGoogle Scholar
  4. 4.
    Dangas G, Iakovou I, Nikolsky E, Aymong ED, Mintz GS, Kipshidze NN, Lansky AJ, Moussa I, Stone GW, Moses JW, Leon MB, Mehran R (2005) Contrast-induced nephropathy after percutaneous coronary interventions in relation to chronic kidney disease and hemodynamic variables. Am J Cardiol 95:13–19. doi: 10.1016/j.amjcard.2004.08.056 PubMedCrossRefGoogle Scholar
  5. 5.
    Toprak O, Cirit M, Yesil M, Bayata S, Tanrisev M, Varol U, Ersoy R, Esi E (2007) Impact of diabetic and pre-diabetic state on development of contrast-induced nephropathy in patients with chronic kidney disease. Nephrol Dial Transplant 22:819–826. doi: 10.1093/ndt/gfl636 PubMedCrossRefGoogle Scholar
  6. 6.
    Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, Mintz GS, Lansky AJ, Moses JW, Stone GW, Leon MB, Dangas G (2004) A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol 44:1393–1399PubMedGoogle Scholar
  7. 7.
    Levy EM, Viscoli CM, Horwitz RI (1996) The effect of acute renal failure on mortality. A cohort analysis. JAMA 275:1489–1494. doi: 10.1001/jama.275.19.1489 PubMedCrossRefGoogle Scholar
  8. 8.
    Gruberg L, Mehran R, Dangas G, Mintz GS, Waksman R, Kent KM, Pichard AD, Satler LF, Wu H, Leon MB (2001) Acute renal failure requiring dialysis after percutaneous coronary interventions. Catheter Cardiovasc Interv 52:409–416. doi: 10.1002/ccd.1093 PubMedCrossRefGoogle Scholar
  9. 9.
    Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr (2002) Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 105:2259–2264. doi: 10.1161/01.CIR.0000016043.87291.33 PubMedCrossRefGoogle Scholar
  10. 10.
    Fishbane S, Durham JH, Marzo K, Rudnick M (2004) N-acetylcysteine in the prevention of radiocontrast-induced nephropathy. J Am Soc Nephrol 15:251–260. doi: 10.1097/01.ASN.0000107562.68920.92 PubMedCrossRefGoogle Scholar
  11. 11.
    Gruberg L, Mintz GS, Mehran R, Gangas G, Lansky AJ, Kent KM, Pichard AD, Satler LF, Leon MB (2000) The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol 36:1542–1548. doi: 10.1016/S0735-1097(00)00917-7 PubMedCrossRefGoogle Scholar
  12. 12.
    Bakris GL, Lass N, Gaber AO, Jones JD, Burnett JC (1990) Radiocontrast medium-induced declines in renal function: a role for oxygen free radicals. Am J Physiol 258:115–120Google Scholar
  13. 13.
    Persson PB, Hansell P, Liss P (2005) Pathophysiology of contrast-medium induced nephropathy. Kidney Int 68:14–22. doi: 10.1111/j.1523-1755.2005.00377.x PubMedCrossRefGoogle Scholar
  14. 14.
    Solomon R, Werner C, Mann D, D’Alia J, Silva P (1994) Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med 331:1416–1420. doi: 10.1056/NEJM199411243312104 PubMedCrossRefGoogle Scholar
  15. 15.
    Huber W, Ilgmann K, Page M, Hennig M, Schweigart U, Jeschke B, Lutilsky L, Weiss W, Salmhofer H, Classen M (2002) Effect of theophylline on contrast material-nephropathy in patients with chronic renal insufficiency: controlled, randomized, double-blinded study. Radiology 223:772–779. doi: 10.1148/radiol.2233010609 PubMedCrossRefGoogle Scholar
  16. 16.
    Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A, Fan K, Lee CH, Lam WF (2003) Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial. JAMA 289:553–558. doi: 10.1001/jama.289.5.553 PubMedCrossRefGoogle Scholar
  17. 17.
    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 (2003) Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 348:491–499. doi: 10.1056/NEJMoa021833 PubMedCrossRefGoogle Scholar
  18. 18.
    Kelly AM, Dwamena B, Cronin P, Bernstein SJ, Carlos RC (2008) Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy. Ann Intern Med 148(4):284–294PubMedGoogle Scholar
  19. 19.
    Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush RS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA, Rittase RA, Norton HJ, Kennedy TP (2004) Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 291:2328–2334. doi: 10.1001/jama.291.19.2328 PubMedCrossRefGoogle Scholar
  20. 20.
    Hill S, Fowler S, Sikand H, Phillips P (2005) Comparison of oral N-actylcysteine versus intravenous sodium bicarbonate in contrast-induced nephropathy treatment (CONVICT Trial). Pharmacotherapy 25(10):1433Google Scholar
  21. 21.
    Saidin R, Zainudin S, Kong NCT et al (2006) Intravenous sodium bicarbonate versus normal saline infusion as prophylaxis against contrast nephropathy in patients with chronic kidney disease undergoing coronary angiography or angioplasty. J Am Soc Nephrol 17:766AGoogle Scholar
  22. 22.
    Addad F, Gamra H, Jemmali M, Dridi Z, Ben Hamda K, Bethout F, Maatoug F, Ben Farhat M (2006) Acetylcysteine versus bicarbonate or combination to prevent contrast-induced nephropathy in patients with diabetes and chronic renal insufficiency: ABC contrast study. Eur Heart J 27(Suppl 1):246–247Google Scholar
  23. 23.
    Recio-Mayoral A, Chaparro M, Prado B, Cózar R, Méndez I, Banerjee D, Kaski JC, Cubero J, Cruz JM (2007) The reno-protective effect of hydration with sodium bicarbonate plus N-acetylcysteine in patients undergoing emergency percutaneous coronary intervention: the RENO Study. J Am Coll Cardiol 49:1283–1288. doi: 10.1016/j.jacc.2006.11.034 PubMedCrossRefGoogle Scholar
  24. 24.
    Briguori C, Airoldi F, D’Andrea D, Bonizzoni E, Morici N, Focaccio A, Michev I, Montorfano M, Carlino M, Cosgrave J, Ricciardelli B, Colombo A (2007) Renal insufficiency following contrast media administration trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation 115:1211–1217PubMedGoogle Scholar
  25. 25.
    Mora JA, Macaraeg CR, Mora RC (2007) Urinary alkalinization and contrast nephropathy. World Congress of Nephrology, T-PO-1650, p 513Google Scholar
  26. 26.
    Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O, Baris N, Aslan O, Badak O (2007) Sodium bicarbonate, N-acetylcysteine, and saline for prevention 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 154(3):539–544. doi: 10.1016/j.ahj.2007.05.012 PubMedCrossRefGoogle Scholar
  27. 27.
    Lin M, Sabeti M, Iskander E, Malhotra N, Pham PTT, Pham PCT (2007) Prevention of contrast nephropathy with sodium bicarbonate. American Sciety of Nephrology Renal Week, PUB591Google Scholar
  28. 28.
    Masuda M, Yamada T, Mine T, Morita T, Tamaki S, Tsukamoto Y, Okuda K, Iwasaki Y, Hori M, Fukunami M (2007) Comparison of usefulness of sodium bicarbonate versus sodium chloride to prevent contrast-induced nephropathy in patients undergoing an emergent coronary procedure. Am J Cardiol 100(5):781–786. doi: 10.1016/j.amjcard.2007.03.098 PubMedCrossRefGoogle Scholar
  29. 29.
    Shaikh F, Maddikunta R, Museitif R, Haddadian B, Dochee J, Qureshi J, Wallach JD, Solis J, Tumuluri R, Bajwa T, Allaqaband S (2007) A prospective randomzed trial comparing normal saline and sodium bicarbonate with or without N-acetylcysteine for prevention of contrast-induced nephropathy. Am J Cardiol 100(8A):122L–123L (Suppl S)Google Scholar
  30. 30.
    Kim H, Kim KS, Shin JH, Lee CH, Kang CM (2007) Hydration with sodium bicarbonate for the preventon of radio contrast-induced nephropathy. Nephrol Dial Transplant 22(Suppl 6):49Google Scholar
  31. 31.
    Chen H, Wu H, He Q, Chen H (2007) Comparison of sodium bicarbonate and sodium chloride as strateges for preventing contrast nephropathy. J Am Soc Nephrol 18:817A. doi: 10.1681/ASN.2006091021 CrossRefGoogle Scholar
  32. 32.
    Heguilen R, Liste A, Rosende G et al (2007) Prevention of contrast-induced nephropathy: volume expansion, N-actylcysteine or both? Results from a pilot study. Nephrol Dial Transplant 22(Suppl 6):54Google Scholar
  33. 33.
    Adolph E, Holdt-Lehmann B, Chatterjee T, Paschka S, Prott A, Schneider H, Koerber T, Ince H, Steiner M, Schuff-Werner P, Nienaber CA (2008) Renal insufficiency following radio contrast exposure trial (REINFORCE): a randomized comparison of sodium bicarbonate versus sodium chloride hydration for the prevention of contrast-induced nephropathy. Coron Artery Dis 19(6):413–419PubMedGoogle Scholar
  34. 34.
    Maioli M, Toso A, Leoncini M, Gallopin M, Tedeschi D, Micheletti C, Bellandi F (2008) Sodium bicarbonate versus saline for the prevention of contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. J Am Coll Cardiol 52(8):599–604. doi: 10.1016/j.jacc.2008.05.026 PubMedCrossRefGoogle Scholar
  35. 35.
    Masuda M, Yamada T, Okuyama Y, Morita T, Sanada S, Furukawa Y, Tsukamoto Y, Okuda K, Iwasaki Y, Yasui T, Fukunami M (2008) Sodium bicarbonate improves long-term clinical outcomes compared with sodium chloride in patients with chronic kidney disease undergoing an emergent coronary procedure. Circ J 72(10):1610–1614. doi: 10.1253/circj.CJ-08-0368 PubMedCrossRefGoogle Scholar
  36. 36.
    Brar SS, Shen AY, Jorgensen MB, Kotlewski A, Aharonian VJ, Desai N, Ree M, Shah AI, Burchette RJ (2008) Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA 300(9):1038–1046. doi: 10.1001/jama.300.9.1038 PubMedCrossRefGoogle Scholar
  37. 37.
    From AM, Bartholmai BJ, Williams AW, Cha SS, Pflueger A, McDonald FS (2008) Sodium bicarbonate is associated with an increased incidence of contrast nephropathy: a retrospective cohort study of 7977 patients at mayo clinic. Clin J Am Soc Nephrol 3(1):10–18. doi: 10.2215/CJN.03100707 PubMedCrossRefGoogle Scholar
  38. 38.
    Schmidt P, Pang D, Nykamp D, Knowlton G, Jia H (2007) N-acetylcysteine and sodium bicarbonate versus N-acetylcysteine and standard hydration for the prevention of radiocontrast-induced nephropathy following coronary angiography. Ann Pharmacother 41(1):46–50. doi: 10.1345/aph.1H354 PubMedGoogle Scholar
  39. 39.
    Hogan SE, L’Allier P, Chetcuti S, Grossman PM, Nallamothu BK, Duvernoy C, Bates E, Moscucci M, Gurm HS (2008) Current role of sodium bicarbonate-based preprocedural hydration for the prevention of contrast-induced acute kidney injury: a meta-analysis. Am Heart J 156(3):414–421. doi: 10.1016/j.ahj.2008.05.014 PubMedCrossRefGoogle Scholar
  40. 40.
    Navaneethan SD, Singh S, Appasamy S, Wing RE, Sehgal AR (2009) Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: A systematic review and meta-analysis. Am J Kidney Dis 53(4):617–627PubMedCrossRefGoogle Scholar
  41. 41.
    Jadad A, Moore R, Carrol D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12. doi: 10.1016/0197-2456(95)00134-4 PubMedCrossRefGoogle Scholar
  42. 42.
    Tepel M, Aspelin P, Lameire N (2006) Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation 113(14):1799–1806. doi: 10.1161/CIRCULATIONAHA.105.595090 PubMedCrossRefGoogle Scholar
  43. 43.
    Nash K, Hafeez A, Hou S (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis 39(5):930–936. doi: 10.1053/ajkd.2002.32766 PubMedCrossRefGoogle Scholar
  44. 44.
    Rosenstock JL, Bruno R, Kim JK, Lubarsky L, Schaller R, Panagopoulos G, DeVita MV, Michelis MF (2008) The effect of withdrawal of ACE inhibitors or angiotensin receptor blockers prior to coronary angiography on the incidence of contrast-induced nephropathy. Int Urol Nephrol 40(3):749–755. doi: 10.1007/s11255-008-9368-1 PubMedCrossRefGoogle Scholar
  45. 45.
    Lima RS, Marques CN, Silva Júnior GB, Barbosa AS, Barbosa ES, Mota RM, Araújo SM, Gutiérrez-Adrianzén OA, Libório AB, Daher EF (2008) Comparison between early and delayed acute kidney injury secondary to infectious disease in the intensive care unit. Int Urol Nephrol 40(3):731–739. doi: 10.1007/s11255-008-9352-9 PubMedCrossRefGoogle Scholar
  46. 46.
    Barrett BJ, Carlisle EJ (1993) Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 188(1):171–178PubMedGoogle Scholar
  47. 47.
    Julian BA, Galla JH, Guthrie GP Jr, Kotchen TA (1982) Renin and aldosterone responses to short-term NaCl or NaHCO3 loading in man. J Lab Clin Med 100(2):261–268PubMedGoogle Scholar
  48. 48.
    Halliwell B, Gutteridge JM (1990) Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186:1–85. doi: 10.1016/0076-6879(90)86093-B PubMedCrossRefGoogle Scholar
  49. 49.
    Baroni EA, Costa RS, Volpini R, Coimbra TM (1999) Sodium bicarbonate treatment reduces renal injury, renal production of transforming growth factor-beta, and urinary transforming growth factor-beta excretion in rats with doxorubicin-induced nephropathy. Am J Kidney Dis 34(2):328–337. doi: 10.1016/S0272-6386(99)70363-X PubMedCrossRefGoogle Scholar
  50. 50.
    Persson PB, Hansell P, Liss P (2005) Pathophysiology of contrast medium-induced nephropathy. Kidney Int 68(1):14–22. doi: 10.1111/j.1523-1755.2005.00377.x PubMedCrossRefGoogle Scholar
  51. 51.
    Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT (2000) Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 275(33):25130–25138. doi: 10.1074/jbc.M001914200 PubMedCrossRefGoogle Scholar
  52. 52.
    Sporer H, Lang F, Oberleithner H, Greger R, Deetjen P (1981) Inefficacy of bicarbonate infusions on the course of postischaemic acute renal failure in the rat. Eur J Clin Invest 11(4):311–315. doi: 10.1111/j.1365-2362.1981.tb02122.x PubMedCrossRefGoogle Scholar
  53. 53.
    Cohen G (1985) The fenton reaction. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 55–64Google Scholar

Copyright information

© Springer Science+Business Media, B.V. 2009

Authors and Affiliations

  • Mehmet Kanbay
    • 1
  • Adrian Covic
    • 2
  • Steven G. Coca
    • 3
    • 4
  • Faruk Turgut
    • 1
  • Ali Akcay
    • 1
  • Chirag R. Parikh
    • 3
    • 4
  1. 1.Department of Internal Medicine, Section of NephrologyFatih University School of MedicineAnkaraTurkey
  2. 2.Department of Nephrology Clinic and Dialysis and Transplantation CenterC. I. Parhon University HospitalIasiRomania
  3. 3.Clinical Epidemiology Research CenterVeterans Affairs Medical CenterWest HavenUSA
  4. 4.Department of MedicineYale University School of MedicineNew HavenUSA

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