| Abstract|| |
Renal ischemia and direct toxic effect of contrast media are the main confounding causes of contrast-induced nephropathy (CIN). The effect of different contrast mediums on the resistance of renal artery is quite unclear. The aim of the present study was to assess the resistive index (RI) changes of renal segmental artery in color Doppler duplex sonography after injection of two different contrast mediums: iodixanol and iohexol. The RI of the renal segmental artery of 62 randomly chosen patients, with a normal baseline renal function, was calculated using color-coded Doppler sonography before and five minutes after bolus injection of two different contrast mediums. Thirty-one patients were administered 50 mL of iodixanol (Visipaque) and 31 patients were administered 50 mL of iohexol (Omnipaque) during intravenous urogram procedures. The RI results were analyzed and compared in two groups using two-tailed t-test. The mean RI of renal segmental artery increased significantly after administration of contrast media (mean ± SD 0.61 ± 0.046 vs 0.58 ± 0.042; p< 0.001). The mean change of RI was 0.0387 ± .00552 (mean ± SE) in the setting of iohexol injection and 0.0216 ± .00423 (mean ± SE) five minutes after administration of iodixanol (p= 0.017). Both non-ionic iso-osmolar dimeric iodixanol and low-osmolar iohexol increase the renal artery resistance, but the changes are more dramatic with iohexol, suggesting better tolerance with iodixanol.
Keywords: Doppler sonography, Iodixanol, Iohexol, Renal segmental artery, Resistive index
|How to cite this article:|
Shakourirad A, Ataeefar M, Jozaghi S. Assessment of the effect of radio contrast media on resistive index of renal artery by color doppler sonography. Saudi J Kidney Dis Transpl 2009;20:91-6
|How to cite this URL:|
Shakourirad A, Ataeefar M, Jozaghi S. Assessment of the effect of radio contrast media on resistive index of renal artery by color doppler sonography. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2022 Nov 28];20:91-6. Available from: https://www.sjkdt.org/text.asp?2009/20/1/91/44712
| Introduction|| |
Contrast induced nephropathy (CIN) is defined as an acute decline in renal function, manifested by an increase in the serum creatinine concentration of at least 0.5 mg/dL or a relative increase of at least 25% from the baseline value within 3 days of administration of contrast media.  It is an increasing cause of hospitalacquired acute kidney injury,  and is accompanied by high morbidity, lengthy hospitalization, and a higher mortality rate. ,,,, Iodinated contrast is the mainstay for diagnostic and interventional procedures performed by cardiologists, radiologists, and other specialists and its usage is expected to increase dramatically over the next few years. Accordingly,  prevalence of CIN may also increase. ,
In recent decades, there has been a considerable refinement in manufacturing contrast media from ionic high-osmolar, to nonionic lowosmolar (LOCM and finally to nonionic isoosmolar contrast media (IOCM).  Iodixanol (Visipaque) is a dimeric iodinated contrast medium that is iso-osmolar to human plasma (290 mosm/kg) at all concentrations.  Initial studies reported that iodixanol was well tolerated and showed its benefits over the low and high osmolar contrast media.  This effect has been reported to be more significant in patients with a previous renal impairment.  In low risk patients, however, iodixanol and iohexol had similar effects. ,,,
Changes in renal hemodynamics, especially the vasoconstrictive effect of contrast media is thought to be the main confounding factor in CIN.  However, the effect of different contrast media over the renal artery resistance is unclear.
We conducted this study to evaluate and compare the intrarenal hemodynamic changes following administration of iodixanol (non-ionic IOCM) and iohexol (Omnipaque, non-ionic LOCM) using color-coded duplex ultrasound.
| Material and Methods|| |
This randomized clinical trial was conducted on 62 patients (25 female and 37 male, with the mean age of 44 years and mean weight of 75 kg) in Sina Hospital. The patients were randomly selected from a group of patients undergoing intravenous urogram procedure and assigned to Visipaque or Omnipaque group. Patients were examined by color-coded duplex ultrasound, with monitoring of intrarenal Doppler signals before and after intravenous injections of contrast media. Thirty-one patients (13 female, 18 male) received Visipaque, while the rest (12 female, 19 male) received Omnipaque injection. All patients had normal renal function with a maximum creatinine level of 1 mg/dL.
None of the patients had a history of diabetes mellitus, peripheral vascular disease, renal parenchymal disease, hydronephrosis on ultrasound, renal failure, and urinary tract infection. None of the patients were taking theophylline or other medications known to interfere with contrast media-induced vasomotor changes.
The study protocol was approved by Research Ethics Committee of Tehran University of Medical Sciences. Informed consents were obtained before enrollment of the patients.
A real time/color-coded duplex scanner (SSD 1700, Aloka, Japan) was used by the same examiner, with the imaging and Doppler systems operated at 3.5 MHz. The patients were examined in a supine position using a lateral or postero-lateral approach. Based on an initial BMode examination, at least one morphologically normal kidney was identified and further examined by duplex sonography before the radio contrast media injection. Under imaging guidance of the color signal, the sample Doppler volume (3mm) was directed toward a segmental artery. The Doppler signals were registered for at least three systolic phases. As a measure of intrarenal flow resistance, the RI was calculated from the Doppler flow curves [Figure 1]. This measurement was defined as a base line.
Five minutes after the bolus intravenous injection of 50 mL radio-contrast media Visipaque (Solution 320, Amersham Health, Cork, Ireland) or Omnipaque (Solution 300, Amersham Health, Cork, Ireland) RI measurement was obtained.
| Statistical analysis|| |
Statistical calculations were preformed with the aid of SPSS version 13. The comparison of the consecutive resistive indices after injection of radio contrast media to the value prior to intravenous contrast application was calculated by two-tailed t-test for paired samples. P< 0.001 was considered statistically significant.
| Results|| |
The comparison of the mean resistive indices before and five minutes after the administration of 50 ml of iodixanol or iohexol by using paired sample t-test, indicated a greater mean resistive index after injection of contrast media compared to the baseline (mean 0.61 ± 0.046, 0.58 ± 0.042 respectively, 95% CI:0. 229-0.374, p< 0.0001).
Independent sample t-test indicated that the mean increase of the RI after administration of iodixanol was less than that after injection of iohexol (0.0387 ± .00552 vs 0.0216 ± .00423 respectively, p= 0.017), suggesting more vasoconstriction after the injection of iohexol.
| Discussion|| |
For several years, high osmolar contrast media (HOCM) have been manufactured in polar (ionic) forms in order to ensure good visualization and water solubility.  Since the earliest report of CIN more than 35 years ago,  some other chemical agents with different osmolalities and compositions (non-ionic vs. ionic, dimer vs. monomer) have been manufactured. 
Although low-osmolar contrast media (LOCM) had 2-3 times lowers osmolarity than high osmolar contrast media (HOCM), they are still associated with development of CIN but to a lesser extent. ,,, More recently non-ionic and IOCM further reduced the risk of CIN.  Comparative studies in patients with normal renal function using non-ionic and iso-osmolar contrast media have shown clinically insignificant effects. ,,,
Several mechanisms are implicated in the de velopment of CIN. , In general, the reduction in renal blood flow and direct toxic effects on renal tubular epithelial cells have been proposed as the major mechanism of CIN.  Contrast media stimulated release of vasoactive substances such as endothelin and adenosine  result in intrarenal vasoconstriction and thus reduced GFR and exacerbation of ischemia . Furthermore, diuresis and natriuresis induced by hyperosmolar contrast media stimulate the tubuloglomerular feedback and reduce GFR. 
Animal studies have confirmed a vasoconstrictive effect of the contrast media on renal artery after an initial vasodilation,  causing a transient decrease in glomerular filtration rate  and a decrease in renal blood flow from 15% to 50%. , Color-coded Doppler ultrasound studies have shown a significant transient increase in renal artery resistance within minutes of intravenous contrast media injection. 
Diagnostic value of the doppler ultrasonography of the renal vessels has proven its utility in different clinical situations. The analysis of intrarenal arterial Doppler flow profiles provides a noninvasive method to investigate pathophysiologic effects of radiocontrast media induced nephrotoxicity. 
The non-ionic dimer iodixanol is characterized by isotonicity with plasma at all iodine concentrations, and is associated with a 71% relative risk reduction for CIN compared with lowosmolar agents in head-to-head randomized trials. 
Experimental and clinical studies note that RI of renal arteries may be altered by vascular compliance,  ureteral obstruction, changes in renal perfusion pressure,  tubulointertitial changes,  and systemic vascular disease.  In the present study, in patients with normal renal function and normal size and artery flow rates of the kidney at initial evaluation by color Doppler sonography showed higher resistive index after administration of iohexol than iodixanolindicative of a greater vasoconstriction with the former.
It is mentioned above that so much evidence compel that iso-osmolar contrast media is better tolerated by kidneys with baseline-impaired function than low osmolar contrast media. The main outcome measure of these studies has been serum creatinine level. Our results are in concordance with these studies, because if a kidney has an impaired function it is less probable to compensate and tolerate the vasoconstrictive effect of the contrast media. In comparison to LOCM, Iodixanol (IOCM) seems to be better tolerated by kidneys with normal as well as with baseline impaired function nevertheless. However, other studies did not find a significant difference in the incidence of CIN after administration of iso-osmolar and low-osmolar contrast media. ,,,, In these studies CIN was defined as an increase of serum creatinine level or a decrease in creatinine clearance after administration of contrast media. Color Doppler ultrasonography is probably a more sensitive method for evaluation of the toxicity of different contrast media than the serum creatinine level as several factors can influence the latter. The increase of the resistive index 5 minutes after the administration of the contrast media, in our patients, suggests vasoconstriction. Immediate increase in RI therefore, provides an early detection of CIN compared to serum creatinine which may take up to 72 hours to increase.
In conclusion, patients with normal renal function may manifest a statistically significant vasoconstrictive effect of iohexol in comparison with Iodixanol. Color-coded Doppler ultrasonography was effective and a simple noninvasive method in evaluating the vascular changes after administration of radio contrast media.
| Acknowledgement|| |
The authors would like to thank Farzan Institute for Research and Technology for technical assistance.[Table 1]
| References|| |
|1.||Morcos SK. Contrast media-induced nephrotoxicity: Questions and answers. Br J Radiol 1998;71:357-65. [PUBMED] [FULLTEXT]|
|2.||Feldkamp T, Baumgart D, Elsner M, et al. Nephrotoxicity of iso-osmolar versus lowosmolar contrast media is equal in low risk patients. Clin Nephrol 2006;66(5):322-30. |
|3.||Krusova D, Sevela K, Kralova D, Zak P, Olovska V. Risky medication and contrast media-induced nephropathy in patients with diabetes and hypertension. Vnitr Lek 2006;52(11):1014-20. |
|4.||Schultz MJ, Baas MC, van der Sluijs HP, Stamkot GA, Smit W. N-acetylcysteine and other preventive measures for contrast-induced nephropathy in the intensive care unit. Curr Med Chem 2006;13(21):2565-70. |
|5.||McCullough PA, Wolyn R, Rocher IL, Levin RN, O'Neill WW. Acute renal failure after coronary intervention: Incidence, risk factors, and relationship to mortality. Am J Med 1997;103(5):368-75. |
|6.||Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality: a cohort analysis. JAMA 1996;275(19):1489-94. |
|7.||Shusterman N, Strom BL, Murray TG, Morrison G, West SL, Maislin G. Risk factors and outcome of hospital-aquired acute renal failure: Clinical epidemiologic study. Am J Med 1987; 83:65-71. |
|8.||McCullough PA. Renal safety of iodixanol. Expert Rev Cardiovasc Ther 2006;4(5) :655-61. |
|9.||Grynne BH, Nossen JO, Bolstad B, Borch KW. Main results of the first comparative clinical studies on Visipaque. Acta Radiol Suppl 1995; 399:265-70. [PUBMED] |
|10.||Hsieh Y, Liu T, Liang K, et al. Iso-osmolar contrast medium better preserves short- and long-term renal function after cardiovascular catheterizations in patients with severe baseline renal insufficiency. Int J Cardiol 2006;111(1) :182-4 |
|11.||Berg KJ. Nephrotoxicity related to contrast media. Scand J Urol Nephrol 2000;34(5):31722. |
|12.||Murakami R, Tjima H, Kumazaki T, Yamamoto K. Effect of iodixanol on renal function immediately after abdominal angiography: clinical comparison with iomeprol and ioxaglate. Acta Radiol 1998;39(4):368-71. |
|13.||Morcos SK, El Nahas AM. Advances in the understanding of the nephrotoxicity of radiocontrast media. Nephron 1998;78(3):249-52. |
|14.||Tumlin J, Stacul F, Adam A, et al. CIN Consensus Working Panel. Pathophysiology of contrast-induced nephropathy. Am J Cardiol 2006;98A:14-20. |
|15.||Goldfarb S. Contrast-induced nephropathy: risk factors, pathophysiology, and prevention. Appl Radiol Online 2005;34:5-16. |
|16.||McCullough PA, Bertrand ME, Brinker JA, Stacul F. A meta-analysis of the renal safety of isosmolar iodixanol compared with low-osmolar contrast media. J Am Coll Cardiol 2006;48(4): 692-9. |
|17.||Rudnick MR, Goldfarb S, Wexler L, et al. Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial. The Iohexol Cooperative Study. Kidney Int 1995; 47:254-61. |
|18.||Taliercio CP, Vlietstra RE, Ilstrup DM, et al. A randomized comparison of nephrotoxicity of iopamidol and diatrizoate in high risk patients undergoing cardiac angiography. J Am Coll Cardiol 1991;17(2) :384-90. |
|19.||Lautin EM, Freeman NJ, Schoenfeld AH, et al. Radio-contrast associated renal dysfunction a comparison of lower-osmolality and conventional high-osmolality contrast media. AJR Am J Roentgenol 1991;157(1) :59-65. |
|20.||Barrett BJ, Carlisle EJ. Meta-analysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993; 188(1) :171-8. |
|21.||Jo SH, Youn TJ, Koo BK, 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(5) :924-30. |
|22.||Jakobsen JA. Renal experience with Vsipaque. Eur Radiol 1996;6:16-9. |
|23.||Davidson CJ, Laskey WK, Hermiller JB, et al. Randomized trial of contrast media utilization in high-risk PTCA: The COURT trial. Circulation 2000;101(18) :2172-7. |
|24.||Rudnick MR, Berns JS, Cohen RM, Goldfarb S. Contrast media-associated nephrotoxicity. Semin Nephrol 1997;17(1) :15-26. |
|25.||Andreucci M, Fuiano G, Presta P, et al. Radiocontrast media cause dephosphorylation of Akt and downstream signaling targets in human renal proximal tubular cells. Biochem Pharmacol 2006;72(10) :1334-42. |
|26.||Deray G, Jacobs C. Renal tolerance of nonionic dimers. Invest Radiol 1996;31(6) :372-7. |
|27.||Rauch D, Drescher P, Pereira FJ, Knes JM, Will JA, Madsen PO. Comparison of iodinated contrast media-induced renal vasoconstriction in human, rabbit, dog, and pig arteries. Invest Radiol 1997;32(6) :315-9. |
|28.||Russo D, Minutolo R, Cianciaruso B, Memoli B, Conte G, De Nicola L. Early effects of contrast media on renal hemodynamics and tubular function in chronic renal failure. J Am Soc Nephrol 1995;6(5) :1451-8. |
|29.||Tumlin JA, Wang A, Murray PT, Mathur VS. Fenoldopam mesylate blocks reductions in renal plasma flow after radiocontrast dye infusion: a pilot trial in the prevention of contrast nephropathy. Am Heart J 2002;143(5) :894-903. |
|30.||Hetzel GR, May P, Hollenbeck M, Voiculescu A, Modder U, Grabensee B. Assessment of radioconrtast media induced renal vasoconstriction by color coded doppler sonography. Ren Fail 2001;23(1) :77-83. |
|31.||Bude RO, Rubin JM. Relationship between the resistive index and vascular compliance and resistance. Radiology 1999;211(2) :411-7. |
|32.||Claudon M, Barnewolt CE, Taylor GA, Dunning PS, Gobet R, Badawy AB. Renal blood flow in pigs: Changes depicted with contrast-enhanced harmonic US imaging during acute urinary obstruction. Radiology 1999;212(3) :725-31. |
|33.||Boddi M, Cecioni I, Poggesi L, et al. Renal resistive index early detects chronic tubulointerstitial nephropathy in normo- and hypertensive patients. Am J Nephrol 2006;26(1) :1621. |
|34.||Heine GH, Reichart B, Ulrich C, Kohler H, Girndt M. Do ultrasound renal resistance indices reflect systemic rather than renal vascular damage in chronic kidney disease? Nephrol Dial Transplant 2007;22:163-70. |
Department of Radiology, Sina Hospital, Medical Sciences/University of Tehran, P.O. Box 13185-1678, Tehran
Source of Support: None, Conflict of Interest: None