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Refining the assessment of contrast-induced acute kidney injury: the load-to-damage relationship

Limbruno, Ugo; Picchi, Andrea; Micheli, Andrea; Calabria, Paolo; Cortese, Bernardo; Brizi, Gina; Severi, Silva; De Caterina, Raffaele

Journal of Cardiovascular Medicine: July 2014 - Volume 15 - Issue 7 - p 587–594
doi: 10.2459/JCM.0b013e3283638e56
Original articles: Interventional cardiology

Aims Comparing the nephrotoxicity of individual contrast agents is challenging, as contrast-induced acute kidney injury (CI-AKI), a widely used trial endpoint, is unable to discriminate between contrast-related and contrast-unrelated causes of renal damage. We established a quantitative method to selectively evaluate the dose-dependent nephrotoxic effect of different contrast agents.

Methods We randomized 113 patients undergoing coronary procedures to either iodixanol 320 mg/ml or iobitridol 350 mg/ml. We calculated baseline creatinine clearance (CrCl) and postprocedural change in serum creatinine. We then calculated the regression of the individual iodine load against the creatinine maximum change [load-to-damage relationship (LDR)]. We assumed that its R2 estimates the predictive accuracy of contrast dose-dependent effects on renal function changes, and that the slope of the LDR characterizes the intrinsic nephrotoxicity of the contrast. We also performed a semi-quantitative evaluation of procedural complexity to assess its complementary role in postprocedural AKI.

Results We found significant correlations between contrast load and creatinine changes for both iobitridol (R2: 0.29; P <0.0001) and iodixanol (R2: 0.15; P = 0.00028). The LDR slope was, however, significantly steeper for iobitridol compared with iodixanol (19.03 ± 4.02 vs. 14.50 ± 4.63 Cr*CrCl/I; P <0.001) and in diabetic compared with nondiabetic patients (24.35 ± 4.96 vs. 4.59 ± 3.25 Cr*CrCl/I; P <0.001). Adding the procedural complexity score to the contrast load significantly increased the predictive ability of the regression model for postprocedural renal function changes (P < 0.02 for the R2 increase in overall population), suggesting a role for procedural complexity in postprocedural renal function damage.

Conclusion The LDR slope is a promising method to evaluate the specific contrast-related fraction of postprocedural AKI.

aCardiology Unit, Misericordia Hospital, Grosseto

bInterventional Cardiology, A.O. Fatebenefratelli, Milan

cInstitute of Cardiology and Center of Excellence on Aging, ‘G. d’Annunzio’ University, Chieti, Italy

Correspondence to Raffaele De Caterina, MD, PhD, Institute of Cardiology, ‘G. d’Annunzio’ University – Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy Tel: +39 0871 41512; fax: +39 0871 402817; e-mail:

Received 4 July, 2012

Revised 15 February, 2013

Accepted 31 March, 2013

© 2014 Italian Federation of Cardiology. All rights reserved.