Contrast-Media Induced Nephropathy in Patients Undergoing Coronary Angiography (Part II of II)

Vitor O. Gomes, MD, Patrícia Blaya, MD, Carlos E. Poli de Figueiredo, MD, PhD, Waldomiro Manfroi, MD, PhD, Paulo Caramori, MD, PhD
Vitor O. Gomes, MD, Patrícia Blaya, MD, Carlos E. Poli de Figueiredo, MD, PhD, Waldomiro Manfroi, MD, PhD, Paulo Caramori, MD, PhD
(PART II of II) 7) Hemodialysis. Lehnert et al.,63 in a randomized study, assessed the prophylactic use of hemodialysis for 3 hours in patients with serum creatinine above 1.4 mg/dl who underwent both cardiac and non-cardiac procedures, beginning immediately after the radiographic examination, in an attempt to eliminate the contrast medium and minimize its deleterious effects on the kidneys. The results indicated that this strategy was not useful for preventing CIN. Continuous hemofiltration (10 hours before and 10 hours after the procedure) was also assessed in the prophylaxis of CIN in 54 high-risk patients (Cr > 2.0 mg/dl) undergoing PTCA.64 The results were extremely favorable to hemofiltration in regard to in-hospital mortality (2.4% versus 14.7%) and the need for hemodialysis (0% versus 39%). However, it is worth noting the invasive and extremely expensive nature of that procedure. 8) Theophylline. Theophylline, a nonselective antagonist of the adenosine receptors, was assessed for preventing CIN. The results, however, were inconclusive. In a placebo-controlled randomized study65 comprising 100 patients with previous renal function suppression, the incidence of CIN was significantly reduced from 16% in the group receiving placebo to 4% in the group receiving theophylline in 48 hours. In another prospective randomized study66 comprising 60 patients with the same characteristics, aminophylline + hydration was compared with hydration alone and dopamine + hydration. No significant difference was observed in the incidence of CIN in the 3 groups studied (35% versus 30% versus 50%, respectively). Erley et al.67 also assessed the use of theophylline in a double-blind randomized study comparing hydration in 80 patients with chronic renal failure. The use of theophylline showed no additional benefit to hydration. 9) Angiotensin-converting enzyme inhibitors (ACE inhibitors). The possible role of medullary ischemia mediated by the renin-angiotensin system raised the hypothesis that ACE inhibitors could be useful for preventing CIN. The prophylactic use of captopril was assessed in diabetic patients undergoing coronary angiography.68 The results showed that the drug was useful for preventing CIN in diabetic patients with a significant risk reduction of 79%. In that randomized study, however, only 71 patients were included. Therefore, larger clinical trials are required to confirm the beneficial effects of the ACE inhibitors in this subgroup of patients. 10) Dopamine. Low doses of dopamine have a renal vasodilating effect, causing an increase in the glomerular filtration rate and renal blood flow. Two randomized studies assessed the use of low doses of dopamine for preventing CIN. One of these studies66 compared the use of dopamine combined with hydration, aminophylline combined with hydration, and hydration alone in patients undergoing PTCA. Another study69 with dopamine comprised 66 patients who underwent coronary angiography and were randomized to receive dopamine at the dosage of 2 µg/kg/minute combined with 0.45% saline solution or 0.45% saline solution alone. The results of both studies did not confirm the potential benefit of dopamine in preventing CIN. In addition, in patients with peripheral vascular disease, the use of dopamine may significantly worsen renal function as compared with the use of placebo.69 11) Atrial natriuretic peptide. The atrial natriuretic peptide is an inhibitor of the synthesis of vasopressin, which is a potent vasoconstrictor. Therefore, by improving renal blood flow, the atrial natriuretic peptide could reduce the incidence of CIN. That drug was assessed in the prophylaxis of CIN in a prospective study comprising 247 patients at risk70 who were randomized to receive placebo or atrial natriuretic peptide at 3 different dosages. The results showed that none of the atrial natriuretic peptide dosages assessed were able to reduce the incidence of CIN as compared to placebo. 12) N-acetylcysteine. There is evidence that the production of free radicals in the kidney increases after the administration of contrast media.12 N-acetylcysteine, an antioxidant, also has vasodilating properties because it increases the expression of the nitric oxide synthetase enzyme71 and can prevent contrast-medium induced renal failure both by reducing direct oxidative injury and by improving renal hemodynamic conditions. Tepel et al.72 reported that in patients with previous renal function suppression undergoing contrast-enhanced computed tomography, the administration of N-acetylcysteine at a dosage of 600 mg twice daily for 2 days significantly reduced the incidence of renal dysfunction caused by contrast medium from 21% in the group receiving placebo to 2% in the group receiving the drug. This result was confirmed in another small clinical trial assessing the use of N-acetylcysteine in 54 patients at risk who were undergoing cardiac catheterization.73 Recently, in a placebo-controlled randomized study74 comprising 183 patients with previous renal function suppression undergoing coronary angiography, coronary angioplasty or peripheral angiography, N-acetylcysteine was not useful for preventing CIN in the population studied. A post hoc analysis showed that the drug had a beneficial effect only in the subgroup of patients receiving a small volume of contrast medium (
1. Pendergrass EP, Chamberlin GW, Godfrey EW, Burdick ED. A survey of deaths and unfavorable sequelae following the administration of contrast media. Am J Radiol 1942;48:741–762. 2. Bartels ED, Brun GC, Gammeltoft A, Gjorup PA. Acute anuria following intravenous pyelography in a patient with myelomatosis. Acta Med Scand 1954;40:297–302. 3. Hou SH, Bushinsky DA, Wish JB, et al. Hospital-acquired renal insufficiency: A prospective study. Am J Med 1983;74:243–248. 4. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. A cohort analysis. JAMA 1996;275:1489–1494. 5. Solomon R, Werner C, Mann D, et al. Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med 1994;331:1416–1420. 6. Berkseth RO, Kjellstrand CM. Radiologic contrast-induced nephropathy. Med Clin North Am 1984;68:351–370. 7. Brezis M, Rosen S. Hypoxia of the renal medulla — Its implication for disease. N Engl J Med 1995;332:647–655. 8. Lund G, Einzig S, Rysavy J. Role of ischemia in contrast-induced renal damage: An experimental study. Circulation 1984;9:783–789. 9. Russo D, Minutolo R, Cianciaruso B, et al. Early effects of contrast media on renal hemodynamics and tubular function in chronic renal failure. J Am Soc Nephrol 1995;6:1451–1458. 10. Ziegler TW, Ludens JH, Fanesti DD, Talner LB. Inhibition of active sodium transport by radiographic contrast media. Kidney Int 1975;7:68–75. 11. Bakris GL, Lass N, Gaber AO, et al. Radiocontrast medium-induced declines in renal function: A role for oxygen free radicals. Am J Physiol 1990;258:F115–F120. 12. Parvez Z, Rahman MA, Moncada R. Contrast media-induced lipid peroxidation in the rat kidney. Invest Radiol 1989;24:697–702. 13. Baliga R, Ueda N, Walker PD, et al. Oxidant mechanisms in toxic acute renal failure. Am J Kidney Dis 1997;29:465–477. 14. Katholi RE, Woods T Jr., Taylor GJ. Oxygen free radicals and contrast nephropathy. Am J Kidney Dis 1998;32:64–71. 15. Pflueger A, Larson TS, Nath KA, et al. Role of adenosine in contrast media-induced acute renal failure in diabetes mellitus. Mayo Clin Proc 2000;75:1275–1283. 16. Gross P, Bussemaker E. Endothelin: What role in acute contrast nephropathy? Nephrol Dial Transplant 1996;11:1716–1718. 17. Cronin RE. Renal failure following radiologic procedures. Am J Med Sci 1989;298:342–356. 18. Porter GA. Contrast-associated nephropathy. Am J Cardiol 1989;64:22E–26E. 19. Porter GA. Experimental contrast-associated nephropathy and its clinical implications. Am J Cardiol 1990;66:18F–22F. 20. Taliercio CP, Vlietstra RE, Fisher LD, Burnett JC. Risks for renal dysfunction with cardiac angiography. Ann Int Med 1986;104:501–504. 21. Rich MW, Crecelios CA. Incidence, risk factors and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. Arch Intern Med 1990;150:1237–1242. 22. Parfrey PS, Griffiths SM, Barrett BJ, et al. Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med 1989;320:143–149. 23. McCullough PA, Wolyn R, Rocher LL, et al. Acute renal failure after coronary intervention: Incidence, risk factors and relationship to mortality. Am J Med 1997;103:368–375. 24. Solomon R. Contrast-medium induced acute renal failure. Kidney Int 1998;53:230–242. 25. Gruberg L, Mintz GS, Mehran R, et al. The prognostic implications of further renal function deterioration within 48 hours of interventional coronary procedures in patients with preexistent chronic renal insufficiency. J Am Coll Cardiol 2000;36:1542–1548. 26. Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002;105:2259–2264. 27. Barshay ME, Kaye JH, Goldman R, Coburn JW. Acute renal failure in diabetic patients after intravenous infusion pyelography. Clin Nephrol 1973;1:35–39. 28. Diaz-Bruxo JA, Wagoner RD, Palumbo PG. Acute renal failure after excretory urography in diabetic patients. Ann Intern Med 1995;83:155–158. 29. Ansari Z, Baldwin BS. Acute renal failure due to radiocontrast agents. Nephron 1976;17:28–40. 30. Harkolen S, Kjellstrand CN. Exacerbation of diabetic renal failure following intravenous pyelography. Am J Med 1977;63:939–946. 31. Weinrauch LA, Healy RW, Leland OS, et al. Coronary angiography and acute renal failure in diabetic azotemic nephropathy. Ann Intern Med 1977;86:56–59. 32. Berns AS. Nephrotoxicity of contrast media. Kidney Int 1989;36:730–740. 33. Manske CL, Sprafka JM, Strony JT, Wang Y. Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography. Am J Med 1990;89:615–620. 34. D’Elia JA, Gleason RE, Alday M, et al. Nephrotoxicity from angiographic contrast material: A prospective study. Am J Med 1982;72:719–727. 35. Cochran ST, Wong WS, Roe DJ. Predicting angiographic-induced acute renal impairment: Clinical risk model. Am J Radiol 1983;141:1027–1033. 36. Baim D, Grossmann W. In: Grossman’s Cardiac Catheterization, Angiography and Intervention, 6th Edition. Lipincott Williams & Wilkins. pp. 35–65. 37. Porter GA. Radiocontrast-induced nephropathy. Nephrol Dial Transplant 1994;9:146–156. 38. Fang LST, Sirota RA, Ebert TH, Lichtenstein NS. Low-fraction excretion of sodium with contrast-media-induced acute renal failure. Arch Intern Med 1980;140:531–533. 39. Anto HR, Chou SY, Porush JG, Shapiro WB. Infusion intravenous pyelography and renal function: Effects of hypertonic mannitol in patient with chronic renal insufficiency. Arch Intern Med 1981;141:1652–1656. 40. Gelman ML, Rowe JW, Coggins CH, Anthanasoulis C. Effects of an angiographic contrast agent on renal function. Cardiovasc Med 1979;4:313–320. 41. Duan SB, Wu HW, Luo JA, Liu FY. Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast media. Nephron 1999;83:122–125. 42. Iakovou I, et al. Incidence, predictors, and economic impact of contrast induced nephropathy: Results in 8,628 patients treated with percutaneous coronary interventions. Presented at ACC, Atlanta, Georgia, 2002. 43. Tommaso CL. Contrast-induced nephrotoxicity in patients undergoing cardiac catheterization. Cathet Cardiovasc Diagn 1994;31:316–321. 44. Gruberg L, Mehran R, Dangas G, et al. Acute renal failure requiring hemodialysis after percutaneous coronary intervention: In-hospital and one-year outcomes. Proceedings of ACC. Anaheim, California, 2000: pp. 1129–1175. 45. Mueller C, Buerkle G, Buettner H, et al. Prevention of contrast-media-associated nephropathy: Randomized comparison of 2 hydration regimens in 1,620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329–336. 46. Taylor AJ, Hotchkiss D, Morse RW, McCabe JM. A randomized trial of inpatient vs. outpatient hydration protocols for cardiac catheterization in mild-to-moderate renal dysfunction. Chest 1998;114:1570–1574. 47. Golman K, Almen T. Contrast-media-induced nephrotoxicity: Survey and present state. Invest Radiol 1985;20(Suppl):S92–S97. 48. Messana JM, Cielinski DA, Nguyen VD, Humes HD. Comparison of the toxicity of the radiocontrast agents, iopamidol and diatrizoate, to rabbit renal proximal tubule cells in vitro. J Pharmacol Exp Ther 1988;244:1139–1144. 49. Schwab SJ, Hlatky NA, Pieper KS, et al. Contrast nephrotoxicity: A randomized controlled trial of a nonionic and an ionic radiographic contrast agent. N Engl J Med 1989;320:149–153. 50. Rudnick MR, Goldfarb S, Wexler L, et al. Nephrotoxicity of ionic and nonionic contrast media in 1,196 patients: A randomized trial. Kidney Int 1995;47:254–261. 51. Katholi RE, Taylor GJ, Woods WT, et al. Nephrotoxicity of nonionic low-osmolality versus ionic high-osmolality contrast media: A prospective double-blind randomized comparison in human beings. Radiology 1993;186:183–187. 52. Deray G, Bellin MF, Boulechfar H, et al. Nephrotoxicity of contrast media in high-risk patients with renal insufficiency: Comparison of low- and high-osmolar contrast agents. Am J Nephrol 1991;11:309–312. 53. Barrett BJ, Carlisle EJ. Meta-analysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993;188:171–178. 54. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491–499. 55. Cigarroa RG, Lange RA, Williams RH, Hillis LD. Dosing of contrast material to prevent contrast nephropathy in patients with renal disease. Am J Med 1989;86:649–646. 56. Prins BA, Hu RM, Nazario B, et al. Prostaglandin E2 and prostacyclin inhibit the production and secretion of endothelin from cultured endothelial cells. J Biol Chem 1994;269:11938–11944. 57. Paller MS, Manivel JC. Prostaglandins protect kidneys against ischemic and toxic injury by a cellular effect. Kidney Int 1992;42:1345–1354. 58. Koch JA, Plum J, Grabensee B, et al. Prostaglandin E1: A new agent for the prevention of renal dysfunction in high-risk patients caused by radiocontrast media? Nephrol Dial Transplant 2000;15:43–49. 59. Khoury Z, Schlicht JR, Como J, et al. The effect of prophylactic nifedipine on renal function in patients administered contrast media. Pharmacotherapy 1995;15:59–65. 60. Neumayer HH, Junge W, Kufner A, Wenning A. Prevention of radiocontrast-media induced nephrotoxicity by the calcium channel blocker nitrendipine: A prospective randomized clinical trial. Nephrol Dial Transplant 1989;4:1030–1036. 61. Madyoon H, Croushore L, Weaver D, Mathur V. Use of fenoldopam to prevent radiocontrast nephropathy in high-risk patients. Cathet Cardiovasc Diagn 2001;53:341–345. 62. Kini AS, Mitre CA, Kim M, et al. A protocol for prevention of radiographic contrast nephropathy during percutaneous coronary intervention: Effect of selective dopamine receptor agonist fenoldopam. Cathet Cardiovasc Interv 2002;55:169–173. 63. Lehnert T, Keller E, Gondolf K, et al. Effect of hemodialysis after contrast medium administration in patients with renal insufficiency. Nephrol Dial Transplant 1998;13:358–362. 64. Marana I, et al. Prevention of renal function worsening after percutaneous coronary interventions by hemofiltration in patients at high risk for contrast nephropathy. Presented at ACC, Atlanta, Georgia, 2002. 65. Huber W, Ilgmann K, Page M, et al. Effect of theophylline on contrast material-induced nephropathy in patients with chronic renal insufficiency: Controlled, randomized, double-blinded study. Radiology 2002;223:772–779. 66. Abizaid AS, Clark CE, Mintz GS, et al. Effects of dopamine and aminophylline on contrast-induced acute renal failure after coronary angioplasty in patients with preexisting renal insufficiency. Am J Cardiol 1999;83:260–263, A5. 67. Erley CM, Duda SH, et al. Prevention of radiocontrast-media induced nephropathy in patients with preexisting renal insufficiency by hydration in combination with the adenosine antagonist theophylline. Nephrol Dial Transplant 1999;14:1146–1149. 68. Gupta RK, Kapoor A, Tewari S, et al. Captopril for prevention of contrast-induced nephropathy in diabetic patients: A randomized study. Indian Heart J 1999;51:521–526. 69. Gare M, Haviv YS, et al. The renal effect of low-dose dopamine in high-risk patients undergoing coronary angiography. J Am Coll Cardiol 1999;34:1682–1688. 70. Kurnik BR, Allgren RL, Genter FC, et al Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy. Am J Kidney Dis 1998;31:674–680. 71. Safirstein R, Andrade L, Vieira JM. Acetylcysteine and nephrotoxic effects of radiographic contrast agents: A new use for an old drug. N Engl J Med 2000;343:209–212. 72. Tepel N, Van der Giet N, Schwarzfeld C, et al. Prevention of radiographic contrast agent induced reductions in renal function by acetylcysteine. N Engl J Med 2000;343:180–184. 73. Diaz-Sandoval L, Kosowsky B, Losordo D. Acetylcysteine to prevent angiography-related renal tissue injury (APART trial). Am J Cardiol 2002;89:356–358. 74. Briguori C, Manganelli F, Scarpato P, et al. Acetylcysteine and contrast-agent associated nephrotoxicity. J Am Coll Cardiol 2002;40:298–303.