Paediatric CTA: nephrotoxic complications in high concentration iodinated contrast medium administration in children with congenital heart disease

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1 Paediatric CTA: nephrotoxic complications in high concentration iodinated contrast medium administration in children with congenital heart disease Poster No.: C-2319 Congress: ECR 2016 Type: Scientific Exhibit Authors: A. Clemente, F. Avogliero, C. L. Susini, S. Storti, D. Della Latta, D. Chiappino; Massa/IT Keywords: DOI: Pediatric, Cardiovascular system, Contrast agents, CT- Angiography, Computer Applications-Detection, diagnosis, Toxicity, Congenital /ecr2016/C-2319 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 15

2 Aims and objectives Iodinated contrast media (CM) has been used for a long time in conjunction with x-ray procedures as a diagnostic tool, and CM nephrotoxicity is well established since 1955, with many reported studies regarding this complication in the medical literature [1]. Radiographic CM are responsible for 11% of cases of hospital-acquired renal insufficiency, the third most common cause of renal failure after impaired renal perfusion and the use of nephrotoxic medications [2]. Iodinated contrast medium-induced nephropathy (CIN) is a potentially serious complication of diagnostic or interventional procedures leading to dialysis, prolonged hospitalization, increased morbidity and mortality [3]. An overall incidence of CIN in the general population is reported to be % [4]. However, in several patient subsets the prevalence of CIN is significantly higher, in particular, in patients with cardiovascular pathology, like advanced congestive heart failure, compromised left ventricle systolic performance, dehydration, and hypotension [5,6]. The definition of CIN includes three necessary components: (1) an absolute or relative increase in serum creatinine compared to the baseline values; (2) a temporal relationship between the rise in serum creatinine and exposure to a contrast agent, and (3) the exclusion of alternative explanations for renal impairment. The traditional definition of CIN is an increase of 25% or more, or an absolute increase of 0.5 mg/dl or more in serum creatinine from baseline value, at h following the exposure to CM [3]. The first 24 h post-exposure appear to be crucial in the development of CIN. A study of the trajectory of serum creatinine elevation in the randomized Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation trial indicated that in 80% of CIN cases serum creatinine started to rise within the first 24h post-cm exposure, and nearly all patients who progressed to serious renal failure had a rise in serum creatinine within this time frame. The same study showed that patients with less than 0.5 mg/dl rise in serum creatinine within the first 24 h were unlikely to have any clinically meaningful form of CIN [6]. The serum creatinine typically peaks 3-5 days after contrast administration and returns to baseline or near baseline within 1-3 weeks [7]. In particular, for the paediatric age group, although more angiographic studies have been performed for complex congenital heart diseases, the number of studies for the renal effect of CM is limited, especially for the late kidney injury [8-12]. Page 2 of 15

3 Acute kidney injury (AKI) is common after paediatric cardiac surgery, occurring in 5-42%, with an associated mortality of 20-79% depending on the AKI definition used in the study [13-15]. Although serum creatinine was used as a biomarker to evaluate renal function in the guidelines ( AKIN; prifle) [16,17], it has been reported that serum creatinine is not adequate for the prediction of precise outcome [6,18]. Numerous studies have already evaluated the use of serum Cystatin C as an endogenous marker of kidney function in populations at risk to develop AKI, showing, that serum Cystatin C has a superior performance in the diagnostic accuracy of serum creatinine levels in the early detection of impaired kidney function [19,20]. The aim of our work was to assess renal function using as laboratory measurements serum Creatinine and Cystatin C concentrations before and after administration of 370 mg/ml iodinated nonionic contrast medium in a paediatric population with congenital heart disease undergoing pre-surgical Computed Tomography Angiography (CTA). Methods and materials A total of 39 paediatric patients (27 males, 12 females; mean age 3±4years-old - range 0-15), who underwent pre-operative cardiac surgery contrast enhanced CT Angiography between June 2012 and November 2015, were retrospectively examined. All patients underwent a volumetric ECG-gated CT angiographic scan with a 320- row scanner. High-concentration iodinated contrast medium (Iopromide 370) was administered by intravenous injection according to a total volume depending on the patient's weight (0,8 to 1,8ml/kg, mean 1,15 ± 0.21ml/kg). No immediate adverse events related to the contrast medium occurred. Serum Creatinine and Cystatin C concentrations were measured before and at #24h after contrast administration; late creatinine was measured at 28±27 days.the endpoint was the comparison of the serum Creatinine and Cystatin C levels with the baseline value after 24 hours and late concentrations. The estimated GFR (egfr) was measured using both value of serum creatinine, with the formula adapted from Schwartz et al. in 2009, [egfr = * height (cm)/creatinine (mg/dl)]. Page 3 of 15

4 For the statistical analysis continuous variables were expressed as mean ±SD, and categorical variables as proportions (%). The parametric T test was used to compare pre and post contrast values of Creatinine, Cystatin C and GFR. A p value of 0.05 or less was considered to indicate significance. Results Increased serum creatine levels (> 25%) from the baseline was observed after 24 hours in 3/39 patients (7,7%), but in these patients the normal age-adjusted serum creatinine levels was included in the normal range. No difference was found between pre-contrast and 24h serum creatinine (p=0.21) nor between pre and 24h GFR (p=0.14). No patients evidenced an increase of serum Cystatin C levels > 25% from the baseline after 24 hours. A significant difference was observed between pre-contrast and 24h Cystatin C (p<0.01) and between pre-contrast and late Creatinine (p<0.01) with an unexpected reduction of both post-procedural parameters. Follow-up was performed in 33/39 patients after CT evaluation (range: days). After this period no patients presented abnormal serum Creatinine levels. Images for this section: Page 4 of 15

5 Fig. 1: Boxplot of pre-contrast, 24h and late Creatinine value in the population < 2 years (pre-post: p=0,077; pre-late: p=0,0007) Page 5 of 15

6 Fig. 2: Boxplot of pre-contrast, 24h and late Creatinine value in the population > 2 years (pre-post: p=0,440; pre-late: p=0,049) Page 6 of 15

7 Fig. 3: Boxplot of pre-contrast and 24h Cystatin C value in the population < 2 years (prepost: p=0,0026) Page 7 of 15

8 Fig. 4: Boxplot of pre-contrast and 24h Cystatin C value in the population > 2 years (prepost: p=0,008) Page 8 of 15

9 Fig. 5: "Scatter-plot" of the Creatinine determined by pre and post-contrast administration Page 9 of 15

10 Fig. 6: "Scatter-plot" of the Creatinine determined by pre and late-contrast administration Page 10 of 15

11 Fig. 7: "Scatter-plot" of the Cystatin C determined by pre and post-contrast administration Page 11 of 15

12 Fig. 8: "Scatter-plot" of the GFR determined by pre and post-contrast administration Page 12 of 15

13 Conclusion Despite the still existing uncertainty regarding the degree of nephrotoxicity produced by various contrast agents, in the current practice non-ionic low-osmolar CM is a preferred agent in patients with renal impairment. In our paediatric population with congenital heart disease, serum Creatinine and Cystatin C concentrations didn't show changes in renal function. The use of high-concentration iodinated contrast medium of the type and dose employed in this study doesn't seem to be related to a renal damage. Personal information Radiology Dept. - Heart Hospital - CNR-Tuscany Region G. Monasterio Foundation References [1] Rudnick MR, Goldfarb S, Wexler L et al. Nephrotoxicity of ionic and nonionic contrast media in 1, 196 patients: a ran- domized trial. The Iohexol Cooperative Study. Kidney int Jan;47(1): [2] Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis 2002; 39: [3] Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl Apr;(100):S11-5. [4] Lasser EC, Lyon SG, Berry CC. Reports on contrast media reactions: analysis of data from reports to the US Food and Drug Administration. Radiology 1997; 203: [5] Rich MW, Crecelius CA. Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A prospective study. Arch Intern Med 1990; 150: [6] Stevens MA, McCullough PA, Tobin KJ et al. A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study: Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation. J Am Coll Cardiol 1999; 33: Page 13 of 15

14 [7] McCullough PA, Sandberg KR. Epidemiology of contrast-induced nephropathy. Rev Cardiovasc Med 2003; 4(Suppl 5): S3-S9. [8] Dittrich S, Kurschat K, Dahnert I et al. Cyanotic nephropathy and use of nonionic contrast agents during cardiac catheterization in patients with cyanotic congenital heart disease. Cardiol Young Jan;10(1):8-14. [9] Patzer L. Nephrotoxicity as a cause of acute kidney injury in children. Pediatr Nephrol Dec;23(12): [10] Pelech A, Allard S, Hurd R et al. A comparison of iohexol and diatrizoate meglumine in children undergoing cardiac cath- eterization. Invest Radiol Jul;26(7): [11] Senthilnathan S, Gauvreau K, Marshall AC et al. Contrast administration in pediatric cardiac catheterization: dose and adverse events. Catheter Cardiovasc Interv May 1;73(6): [12] Assadi F. Acetazolamide for prevention of contrast induced nephropathy: a new use for an old drug. Pediatr Cardiol Mar-Apr;27(2): [13] Pedersen KR, Povlsen JV, Christensen S, et al. Risk factors for acute renal failure requiring dialysis after surgery for congenital heart disease in children. Acta Anaesthesiol Scand. 2007; 51: [14] Li, S., Krawczeski, CD, Zappitelli M, Devarajan P et al. Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery-a prospective multicenter study. Critical care medicine (6), [15] Hwang YJ, Hyun MC, Choi BS et al. Acute Kidney Injury after Using Contrast during Cardiac Catheterization in Children with Heart Disease. JJ Korean Med Sci Aug;29(8): [16] Akcan-Arikan A, Zappitelli M, Loftis LL et al. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 2007; 71: [17] Mehta RL, Kellum JA, Shah et al. Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31 [18] Al-Ismaili Z, Palijan A, Zappitelli M. Biomarkers of acute kidney injury in children: discovery, evaluation, and clinical application. Pediatr Ne- phrol 2011; 26: [19] Rich MW, Crecelius CA. Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A prospective study. Arch Intern Med 1990; 150: Page 14 of 15

15 [20] Rihal CS, Textor SC, Grill DE et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002; 105: Page 15 of 15