Contrast Dose, Estimated GFR, and Techniques to Reduce Contrast Dose in PCI – Time to Consider Some Basic Principles!

Dear Editor:

Gurm et al have elaborated on the use of the ratio between contrast medium (CM) volume and estimated creatinine clearance (CV/CrCl) to predict the risk of acute kidney injury (AKI) among patients undergoing percutaneous coronary intervention (PCI) in a recent article in the Journal of Invasive Cardiology¹ as well as in a previous publication.² This raises a few issues to discuss, ie, the selection of the equation to estimate CrCl with regard to creatinine assay calibration, expressing CM doses simply in volumes, and an additional option to decrease CM dose simply by reducing the standard concentration used in PCI. 

The authors have chosen the Cockcroft-Gault (CG) equation to estimate CrCl, “since it has been conventionally used for dosing of medications excreted by glomerular filtration.”² I agree that an equation estimating CrCl or glomerular filtration rate (GFR) unadjusted to body surface area (BSA), absolute CrCl/GFR, like the CG equation should be used when evaluating the risk of AKI following CM administration.³ However, it is a prerequisite when adopting a CrCl/GFR equation that it is stated that the calibration of the local creatinine assay equals the one used when developing the equation, to avoid marked overestimation or underestimation of renal function.⁴ The CG equation was developed in 1976 based on a non-standardized creatinine assay and is not compatible with modern creatinine assays traceable to international reference materials introduced about 10 years ago.-⁴ The CG equation has been demonstrated to have substandard accuracy, with marked positive bias in patients with moderate to severe reduction in renal function when today’s standardized creatinine assays are used.⁴ This may have an effect on the presented results.

Treating CM simply as “dye” by using CM volume to express dose, not uncommon in the cardiology CM literature, is somewhat disrespectful since commercially available concentrations of CM vary between 140 and 400 mg I/mL, so dose should be expressed in gram-iodine.^5,6 Although dose should ideally be expressed in moles (number of molecules), not least because iso-osmolar CM contains half the number of CM molecules compared with low-osmolar CM at equi-iodine concentrations. This also raises the issue that CM type needs to be defined since meta-analyses indicate that iso-osmolar CMs are less nephrotoxic than low-osmolar CMs.^7,8

However, the concept of gram-iodine has the advantage that it reflects the diagnostic capacity, the fundamental goal of CM. Furthermore, common gram-iodine doses for angiographic procedures may range from 10 (=50 mL x 200 mg I/mL) to 120 grams of iodine (≈350 mL x 350 mg I/mL), ie, the same numerical range as severely reduced to normal renal function.⁹ Thus, forming a ratio between gram-iodine dose and estimated CrCl/GFR provides the examiner with a simple numerical relationship. A major drawback to simply reporting CM volumes without stating the concentration used is that it makes it difficult to expand the experience of post-CM AKI from one hospital to another or from one type of angiographic examination or interventional procedure to another when different concentrations are used. For example, in digital subtraction angiography of peripheral arteries, concentrations down to 150-200 mg I/mL may be used. Most selective angiographic examinations, eg, coronary, carotid, mesenteric, and aortofemoral, in fact imply an ‘‘indirect’’ renal CM exposure, since the CM has to pass at least two capillary beds before reaching the kidneys.¹⁰ All of these procedures may thus have a similar risk of AKI for the same iodine-dose/GFR ratio irrespective of the particular CM concentration used and providing patients have a similar risk profile. Anticipating that Gurm et al used a standard concentration varying from 320 to 370 mg I/mL for their PCI procedures, a CM-volume/GFR ratio of 3.0 would thus correspond close to a gram-iodine/GFR ratio of 1.05 at a concentration of 350 mg I/mL.

Gurm et al also elaborate on various techniques of limiting CM volume. A simple way to reduce CM dose would be to reduce CM concentration. Before the advent of nephrogenic systemic fibrosis, gadolinium (Gd) CMs were used as an off-label substitute for iodine CMs in azotemic patients at risk of AKI when undergoing coronary arteriography and PCI. Investigators found that 1.0 M Gd-CM or 2:1 and 1:1 mixtures of 0.5 M Gd-CM and I-CM at 320–350 mg I/mL have given satisfactory diagnostic results.^11-13 The attenuation of these solutions would correspond to about 150–200 mg I/mL of a pure I-CM at 70-95 kVp.^14,15 Thus, it appears possible to perform coronary procedures with a markedly reduced CM concentration compared with the standard use of about 320–370 mg I/mL, at least in thinner patients when it is also possible to take advantage of the automatic down-regulation of the x-ray tube potential that increases iodine attenuation. This needs further studies and would require that dose is expressed in gram-iodine for adequate interindividual and interlaboratory comparisons.

References

1.    Gurm HS, Seth M, Mehran R, et al. Impact of contrast dose reduction on incidence of acute kidney injury (AKI) among patients undergoing PCI: a modeling study. J Invasive Cardiol. 2016;28:142-146.

2.    Gurm HS, Dixon SR, Smith DE, et al. Renal function-based contrast dosing to define safe limits of radiographic contrast media in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol. 2011;58:907-914.

3.    Nyman U, Grubb A, Lindström V, Björk J. Accuracy of GFR estimating equations in a large Swedish cohort: implications for radiologists in daily routine and research. Acta Radiol. 2016 May 10 (Epub ahead of print).

4.    Nyman U, Björk J, Bäck SE, Sterner G, Grubb A. Estimating GFR prior to contrast medium examinations – what the radiologist needs to know! Euro Radiol. 2016;26:425-435.

5.    Nyman U, Almén T, Aspelin P, Hellström M, Kristiansson M, Sterner G. Contrast-medium-Induced nephropathy correlated to the ratio between dose in gram iodine and estimated GFR in ml/min. Acta Radiol. 2005;46:830-842.

6.    Nyman U, Björk J, Aspelin P, Marenzi G. Contrast medium dose-to-GFR ratio: a measure of systemic exposure to predict contrast-induced nephropathy after percutaneous coronary intervention. Acta Radiol. 2008;49:658-667.

7.    Dong M, Jiao Z, Liu T, Guo F, Li G. Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials. J Nephrol. 2012;25:290-301.

8.    McCullough PA, Brown JR. Effects of intra-arterial and intravenous iso-osmolar contrast medium (iodixanol) on the risk of contrast-induced acute kidney injury: a meta-analysis. Cardiorenal Med. 2011;1:220-234.

9.    K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Part 4. Definition and classification of stages of chronic kidney disease. Am J Kidney Dis. 2002;39:S46-S75.

10.    Nyman U, Almén T, Jacobsson B, Aspelin P. Are intravenous injections of contrast media really less nephrotoxic than intra-arterial injections? Eur Radiol. 2012;22:1366-1371.

11.    Barcin C, Kursaklioglu H, Iyisoy A, Kose S, Tore HF, Isik E. Safety of gadodiamide mixed with a small quantity of iohexol in patients with impaired renal function undergoing coronary angiography. Heart Vessels. 2006;21:141-145.

12.    Sarkis A, Badaoui G, Azar R, Sleilaty G, Bassil R, Jebara VA. Gadolinium-enhanced coronary angiography in patients with impaired renal function. Am J Cardiol. 2003;91:974-975, A974.

13.    Voss R, Grebe M, Heidt M, Erdogan A. Use of gadobutrol in coronary angiography. Catheter Cardiovasc Interv. 2004;63:319-322.

14.    Nyman U, Elmståhl B, Geijer H, Leander P, Almén T, Nilsson M. Iodine contrast iso-attenuating with diagnostic gadolinium doses in CTA and angiography results in ultra-low iodine doses. A way to avoid both CIN and NSF in azotemic patients? Eur Radiol. 2011;21:326-336.

15.    Swanberg J, Åslund PE, Nyman RS, Nyman UR. Ultra-low iodine concentrations iso-attenuating with diagnostic 0.5M gadolinium in endovascular procedures to minimize the risk of contrast nephropathy: a phantom study. Eur J Radiol. 2015;84:1068-1074.

From the Department of Translational Medicine, Division of Medical Radiology, Skåne University Hospital, Malmö, Sweden.

Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The author reports no conflicts of interest regarding the content herein.

Address for correspondence: Ulf Nyman, MD, PhD, Department of Translational Medicine, Division of Medical Radiology, Skåne University Hospital, SE-205 02 Malmö, Sweden. Email: ulf.nyman@bredband.net