Abstract
Purpose
Contrast-enhanced ultrasonography (CEUS) is a novel approach used for measuring organ perfusion changes. Studies using CEUS to assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on renal blood flow (RBF) have not yet been conducted. We aimed to evaluate the effects of NSAIDs on the renal hemodynamics of healthy subjects with CEUS.
Methods
We performed CEUS using the bolus injection method in a total of 10 healthy subjects. Measurements were completed over two study days in a randomized, crossover manner. On each study day, CEUS was performed twice, before and after the administration of NSAIDs. Subjects received an injection of contrast medium and images were recorded. A region-of-interest (ROI) was selected within the renal cortex, signal intensity in the ROI of the kidney was measured and a time-intensity curve (TIC) was automatically generated with attached software.
Results
The mean (±SD) peak intensity decreased significantly after an administration of diclofenac sodium (from 26.0 × 10−4 ± 17.4 × 10−4 AU to 19.2 × 10−4 ± 12.0 × 10−4 AU; P = 0.022), but not significantly with etodolac (from 26.5 × 10−4 ± 9.7 × 10−4 AU to 25.9 × 10−4 ± 20.8 × 10−4 AU; P = 0.474). The mean (±SD) percent reduction in intensity following diclofenac sodium administration was significantly reduced compared with etodolac administration (22.2 ± 20.5 % vs. 3.4 ± 8.9 %, P = 0.037).
Conclusions
These finding suggests that diclofenac sodium (P = 0.022), but not etodolac (P = 0.474), affects renal hemodynamics even in healthy subjects.
Similar content being viewed by others
References
Kalantarinia K, Belcik JT, Patrie JT, Wei K (2009) Real-time measurement of renal blood flow in healthy subjects using contrast-enhanced ultrasound. Am J Physiol Renal Physiol 297:F1129–F1134
Quaia E (2011) Assessment of tissue perfusion by contrast-enhanced ultrasound. Eur Radiol 21:604–615
Cosgrove D, Lassau N (2010) Imaging of perfusion using ultrasound. Eur J Nucl Med Mol Imaging 37:S65–S85
Bentley MD, Lerman LO, Hoffman EA, Fiksen-Olsen MJ, Ritman EL, Romero JC (1994) Measurement of renal perfusion and blood flow with fast computed tomography. Circ Res 74:945–951
Ritt M, Janka R, Schneider MP, Martirosian P, Hornegger J, Bautz W, Uder M, Schmieder RE (2010) Measurement of kidney perfusion by magnetic resonance imaging: comparison of MRI with arterial spin labeling to para-aminohippuric acid plasma clearance in male subjects with metabolic syndrome. Nephrol Dial Transplant 25:1126–1133
Kudomi N, Koivuviita N, Liukko KE, Oikonen VJ, Tolvanen T, Iida H, Tertti R, Metsärinne K, Iozzo P, Nuutila P (2009) Parametric renal blood flow imaging using [15O]H2O and PET. Eur J Nucl Med Mol Imaging 36:683–691
Kaneko T, Teshigawara O, Sugimoto H, Hirota M, Inoue S, Takeda S, Nakao A (2005) Signal intensity of the liver parenchyma in microbubble contrast agent in the late liver phase reflects advanced fibrosis of the liver. Liver Int 25:288–293
Tousek P, Penicka M, Tintera J, Linkova H, Gregor P (2008) Identification of hibernating myocardium with myocardial contrast echocardiography: comparison with late gadolinium-enhanced magnetic resonance. Int J Cardiol 128:117–120
Hosotani Y, Takahashi N, Kiyomoto H, Ohmori K, Hitomi H, Fujioka H, Aki Y, Fukunaga M, Yuasa S, Mizushige K, Kohno M (2002) A new method for evaluation of split renal cortical blood flow with contrast echography. Hypertens Res 25:77–83
Kishimoto N, Mori Y, Nishiue T, Nose A, Kijima Y, Tokoro T, Yamahara H, Okigaki M, Kosaki A, Iwasaka T (2004) Ultrasound evaluation of valsartan therapy for renal cortical perfusion. Hypertens Res 27:345–349
Tsuruoka K, Yasuda T, Koitabashi K, Yazawa M, Shimazaki M, Sakurada T, Shirai S, Shibagaki Y, Kimura K, Tsujimoto F (2010) Evaluation of renal microcirculation by contrast-enhanced ultrasound with sonazoidTM as a contrast agent: comparison between normal subjects and patients with chronic kidney disease. Int Heart J 51:176–182
Schneider AG, Hofmann L, Wuerzner G, Glatz N, Maillard M, Meuwly JY, Eggimann P, Burnier M, Vogt B (2012) Renal perfusion evaluation with contrast-enhanced ultrasonography. Nephrol Dial Transplant 27:674–681
Weir MR (2002) Renal effects of nonselective NSAIDs and coxibs. Cleve Clin J Med 69(Suppl 1):SI53–SI58
Toto RD, Anderson SA, Brown-Cartwright D, Kokko JP, Brater DC (1986) Effects of acute and chronic dosing of NSAIDs in patients with renal insufficiency. Kidney Int 30:760–768
Nielsen CB, Sørensen SS, Pedersen EB (1994) Identical effects of indomethacin on renal function in healthy uninephrectomized subjects and in healthy control subjects. Clin Sci 86:715–721
Farker K, Merkel U, Schweer H, Haerting J, Madani SF, Eggers R, Müller UA, Seyberth HW, Hoffmann A (2002) Effects of short-term treatment with diclofenac-colestyramine on renal function and urinary prostanoid excretion in patients with type-2 diabetes. Eur J Clin Pharmacol 58:85–91
Fredman B, Zohar E, Golan E, Tillinger M, Bernheim J, Jedeikin R (1999) Diclofenac does not decrease renal blood flow or glomerular filtration in elderly patients undergoing orthopedic surgery. Anesth Analg 88:149–154
Svendsen KB, Bech JN, Sørensen TB, Pedersen EB (2000) A comparison of the effects of etodolac and ibuprofen on renal haemodynamics, tubular function, renin, vasopressin and urinary excretion of albumin and α-glutathione-S-transferase in healthy subjects: a placebo-controlled cross-over study. Eur J Clin Pharmacol 56:383–388
Brater DC, Anderson SA, Brown-Cartwright D, Toto RD, Chen A, Jacob GB (1985) Effect of etodolac in patients with moderate renal impairment compared with normal subjects. Clin Phamacol Ther 38:674–679
Manvelian G, Daniels S, Gibofsky A (2012) The pharmacokinetic parameters of a single dose of a novel nano-formulated, lower-dose oral diclofenac. Postgrad Med 124:117–123
Brater DC, Lasseter KC (1989) Profile of etodolac: pharmacokinetic evaluation in special populations. Clin Rheumatol 8(Suppl 1):25–35
Whelton A (1999) Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 106:13S–24S
Harris RC, Breyer MD (2006) Update on cyclooxygenase-2 inhibitors. Clin J Am Soc Nephrol 1:236–245
Harris RC (2006) COX-2 and the kidney. J Cardiovasc Pharmacol 47(Suppl 1):S37–S42
Conflict of interest
The authors have no conflicts of interest to declare.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Imamura, H., Hata, J., Iida, A. et al. Evaluating the effects of diclofenac sodium and etodolac on renal hemodynamics with contrast-enhanced ultrasonography: a pilot study. Eur J Clin Pharmacol 69, 161–165 (2013). https://doi.org/10.1007/s00228-012-1336-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-012-1336-0