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Multimodality Prevention of Contrast-Induced Acute Kidney Injury
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MULTIMODALITY PREVENTION OF CONTRAST-INDUCED ACUTE KIDNEY INJURY
To the Editor: We read with interest Dr McCullough’s editorial on the REMEDIAL (Renal Insufficiency Following Contrast Media Administration Trial) study.1-2 We would like to make some comments. First, Dr McCullough stated that the study is small and argued that the results may have been due to chance. In a recent review on this topic, however, McCullough stated: “iodixanol has been associated with a 71% relative risk reduction for contrast-induced nephropathy compared with low-osmolar agents in head-to-head randomized trials.”3 Furthermore, in Consensus Statement 6 (Table 1 of the editorial), McCullough stated “iodixanol is associated with the lowest risk of contrast-induced AKI.”1 This very strong statement relies on results from the Nephrotoxic Effects in High-Risk Patients Undergoing Angiography (NEPHRIC) trial, which demonstrated that iodixanol is less nephrotoxic than iohexol.4 This trial included only 129 patients (64 in the group treated with iodixanol). It is quite curious that McCullough takes such a strong stance given that this recommendation is based on a relatively small sponsored trial. Furthermore, Dr McCullough ought to comment on a recent negative randomized trial comparing iodixanol with another lowosmolar contrast agent.5 Second, Dr McCullough reports from the study by Hoffmann et al suggesting that N-acetylcysteine (NAC) reduces serum creatinine levels.6 On the other hand, Izzedine et al demonstrated that NAC did not interfere with serum creatinine assays assessed using the Jaffé method.7 Last, NAC and bicarbonate are very cheap compounds. Iodixanol is much more expensive than all other lowosmolar contrast media. Our studies addressing the effectiveness of NAC and sodium bicarbonate were all self initiated whereas the big trials are all sponsored and thus harbor a possible conflict of interest.8 We agree with Dr McCullough on the necessity of multicenter, large-scale
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randomized trials. However, we believe very strongly that these trials should be performed without sponsorship, a difficult Catch-22. Carlo Briguori, MD, PhD1,2 Flavio Airoldi, MD2 Antonio Colombo, MD2 1 Clinica Mediterranea Naples, Italy 2 “Vita e Salute” University School of Medicine San Raffaele Hospital Milan, Italy
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: None.
REFERENCES 1. McCullough PA: Mutimodality prevention of contrastinduced acute kidney injury. Am J Kidney Dis 51:169-172, 2008 2. Briguori C, Airoldi F, D’Andrea D, et al: Renal insufficiency following contrast media administration trial (REMEDIAL): a comparison of 3 preventive strategies. Circulation 115:1211-1217, 2007 3. McCullough PA: Renal safety of iodixanol. Expert Rev Cardiovasc Ther 4:655-661, 2006 4. Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ: Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 348:491-499, 2003 5. Solomon RJ, Natarajan MK, Doucet S, et al: Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation 115:3189-3196, 2007 6. Hoffmann U, Fischereder M, Krueger B, Drobnik W, Kraemer BK: The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable. J Am Soc Nephrol 15:407-410, 2004 7. Izzedine H, Guerin V, Launay-Vacher V, Bernad M, Deray G: Effect of N-acetylcysteine on serum creatinine level. Nephrol Dial Transplant 16:1514-1515, 2001 8. Ridker PM, Torres J: Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-forprofit organizations: 2000-2005. JAMA 295:2270-2274, 2006 © 2008 by the National Kidney Foundation, Inc. doi:10.1053/j.ajkd.2008.02.364 In Reply: The Consensus Statement 6 (and now an American College of Cardiology/American Heart Association Class IA indication for the use of iodixanol) is based on the metaanalysis of 2,727 patients in head-to-head randomized trials demonstrating 62% and 80% relative risk reductions in all and those with diabetic chronic kidney disease, respectively (P ⬍ 0.001; P ⫽ 0.003).1,2
American Journal of Kidney Diseases, Vol 51, No 6 (June), 2008: pp 1068-1078
MULTIMODALITY PREVENTION OF CONTRAST-INDUCED ACUTE KIDNEY INJURY
To the Editor: We read with interest Dr McCullough’s editorial on the REMEDIAL (Renal Insufficiency Following Contrast Media Administration Trial) study.1-2 We would like to make some comments. First, Dr McCullough stated that the study is small and argued that the results may have been due to chance. In a recent review on this topic, however, McCullough stated: “iodixanol has been associated with a 71% relative risk reduction for contrast-induced nephropathy compared with low-osmolar agents in head-to-head randomized trials.”3 Furthermore, in Consensus Statement 6 (Table 1 of the editorial), McCullough stated “iodixanol is associated with the lowest risk of contrast-induced AKI.”1 This very strong statement relies on results from the Nephrotoxic Effects in High-Risk Patients Undergoing Angiography (NEPHRIC) trial, which demonstrated that iodixanol is less nephrotoxic than iohexol.4 This trial included only 129 patients (64 in the group treated with iodixanol). It is quite curious that McCullough takes such a strong stance given that this recommendation is based on a relatively small sponsored trial. Furthermore, Dr McCullough ought to comment on a recent negative randomized trial comparing iodixanol with another lowosmolar contrast agent.5 Second, Dr McCullough reports from the study by Hoffmann et al suggesting that N-acetylcysteine (NAC) reduces serum creatinine levels.6 On the other hand, Izzedine et al demonstrated that NAC did not interfere with serum creatinine assays assessed using the Jaffé method.7 Last, NAC and bicarbonate are very cheap compounds. Iodixanol is much more expensive than all other lowosmolar contrast media. Our studies addressing the effectiveness of NAC and sodium bicarbonate were all self initiated whereas the big trials are all sponsored and thus harbor a possible conflict of interest.8 We agree with Dr McCullough on the necessity of multicenter, large-scale
1068
randomized trials. However, we believe very strongly that these trials should be performed without sponsorship, a difficult Catch-22. Carlo Briguori, MD, PhD1,2 Flavio Airoldi, MD2 Antonio Colombo, MD2 1 Clinica Mediterranea Naples, Italy 2 “Vita e Salute” University School of Medicine San Raffaele Hospital Milan, Italy
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: None.
REFERENCES 1. McCullough PA: Mutimodality prevention of contrastinduced acute kidney injury. Am J Kidney Dis 51:169-172, 2008 2. Briguori C, Airoldi F, D’Andrea D, et al: Renal insufficiency following contrast media administration trial (REMEDIAL): a comparison of 3 preventive strategies. Circulation 115:1211-1217, 2007 3. McCullough PA: Renal safety of iodixanol. Expert Rev Cardiovasc Ther 4:655-661, 2006 4. Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ: Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 348:491-499, 2003 5. Solomon RJ, Natarajan MK, Doucet S, et al: Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation 115:3189-3196, 2007 6. Hoffmann U, Fischereder M, Krueger B, Drobnik W, Kraemer BK: The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable. J Am Soc Nephrol 15:407-410, 2004 7. Izzedine H, Guerin V, Launay-Vacher V, Bernad M, Deray G: Effect of N-acetylcysteine on serum creatinine level. Nephrol Dial Transplant 16:1514-1515, 2001 8. Ridker PM, Torres J: Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-forprofit organizations: 2000-2005. JAMA 295:2270-2274, 2006 © 2008 by the National Kidney Foundation, Inc. doi:10.1053/j.ajkd.2008.02.364 In Reply: The Consensus Statement 6 (and now an American College of Cardiology/American Heart Association Class IA indication for the use of iodixanol) is based on the metaanalysis of 2,727 patients in head-to-head randomized trials demonstrating 62% and 80% relative risk reductions in all and those with diabetic chronic kidney disease, respectively (P ⬍ 0.001; P ⫽ 0.003).1,2
American Journal of Kidney Diseases, Vol 51, No 6 (June), 2008: pp 1068-1078