NDT Advance Access originally published online on April 29, 2008
Nephrology Dialysis Transplantation 2008 23(7):2424; doi:10.1093/ndt/gfn163
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Conclusion of recent ‘osmolality trials’ in preventing contrast-induced nephropathy by NAC—what is the standard?
Correspondence and offprint requests to: E-mail: sophi5{at}medimail.co.krSir,
We read with great interest Dr Kimmel et al.'s report on the use of cystatin C as a more reliable parameter for estimating GFR and its value in assessing the renoprotective potential of putative prophylactic agents, and we believe that this study makes an important contribution to the scientific literature [1]. However, in the paper's discussion, when explaining their rationale for using a low-osmolar contrast agent, Kimmel et al. incorrectly state that our clinical trial, RECOVER [2], does not support the results of NEPHRIC [3], which concluded that contrast-induced nephropathy (CIN) may be less likely to develop in high-risk patients when the iso-osmolar contrast agent, iodixanol, is used rather than a low-osmolar contrast agent.
NEPHRIC was a double-blind, prospective, multicentre trial in which 129 patients with diabetes and serum creatinine (SCr) levels of 1.5 to 3.5 mg/dL undergoing coronary or aortofemoral angiography were randomized to receive either iodixanol or iohexol, a low-osmolar contrast agent. Defining CIN as an increase in SCr of 
0.5 mg/dL from baseline, Aspelin et al. determined that 3% of patients in the iodixanol group developed CIN compared to 26% of patients in the iohexol group (P = 0.002).
RECOVER was a double-blind, prospective, single-centre trial in which 300 patients with creatinine clearance (CrCl) rates 
60 mL/min undergoing coronary angiography were randomized to receive either iodixanol or ioxaglate, a low-osmolar contrast agent. Technically, if we had used the same definition of CIN as Aspelin et al. (only SCr increase 0.5 mg/dL from baseline), the difference in CIN incidence between iodixanol and ioxaglate would have trended in favour of iodixanol but would not have achieved statistical significance (3.6% versus 8.9%, P = 0.067). However, in our study we used the more common definition of CIN [4,5]—the one used as a study endpoint in [1] and given in the European Society of Urogenital Radiology (ESUR) guidelines [6]—that is, an increase in SCr of 25% or 0.5 mg/dL from baseline, and we determined that 7.9% of patients in the iodixanol group developed CIN compared with 17.0% of patients in the ioxaglate group (P = 0.021). We also investigated the incidence of CIN in subgroups of at-risk patients and found the incidence of CIN to be significantly lower in the iodixanol group compared to the ioxaglate group in patients with severe renal impairment (CrCl <30 mL/min; 12.5% versus 53.3%, P = 0.023) and in those with diabetes (10.4% versus 26.5%, P = 0.041). We concluded that the iso-osmolar contrast agent, iodixanol, was significantly less nephrotoxic than the low-osmolar contrast agent, ioxaglate.
In summary, the RECOVER trial confirmed the findings of the NEPHRIC trial in reporting significantly lower CIN rates with iodixanol when compared to a low-osmolar contrast agent.
Conflict of interest statement. None declared.
1 Division of Cardiology Department of Internal Medicine Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do 2 Division of Cardiology Department of Internal Medicine Seoul National University College of Medicine/Cardiovascular Center Seoul National University Hospital Yongon-Dong, Chongno-Gu, Seoul Korea
References
- Kimmel M, Butscheid M, Brenner S, et al. Improved estimation of glomerular filtration rate by serum cystatin C in preventing contrast induced nephropathy by N-acetylcysteine or zinc—preliminary results. Nephrol Dial Transplant (2008) 23:1241–1245.
[Abstract/Free Full Text] - Jo S-H, Youn T-J, Koo B-K, et al. Renal toxicity evaluation and comparison between Visipaque® (iodixanol) and Hexabrix® (ioxaglate) in patients with renal insufficiency undergoing coronary angiography—the RECOVER study: a randomized controlled trial. J Am Coll Cardiol (2006) 48:924–930.
[Abstract/Free Full Text] - Aspelin P, Aubry P, Fransson S-G, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med (2003) 348:491–499.
[Abstract/Free Full Text] - Gleeson TG, Bulugahapitiya S. Contrast-induced nephropathy. AJR Am J Roentgenol (2004) 183:1673–1689.
[Free Full Text] - McCullough PA, Adam A, Becker CR, et al. Epidemiology and prognostic implications of contrast-induced nephropathy. Am J Cardiol (2006) 98(Suppl_6A):5K–13K.[Web of Science][Medline]
- Thomsen HS, Morcos SK. Contrast media and the kidney: European Society of Urogenital Radiology (ESUR) guidelines. Br J Radiol (2003) 76:513–518.
[Abstract/Free Full Text]
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