Abstract
Introduction: Changes in renal hemodynamics are suspected to be one of the major pathogenetic correlates in radiocontrast media-induced nephrotoxicity. We investigated whether color-coded duplex sonography is an appropriate method to document changes in intrarenal vascular resistance, after intravenous injection of the low-osmolar contrast material Iopamidol. Methods: Intrarenal arterial doppler wave forms were analyzed every minute after intravenous injection of 100 mL Iopamidol in 10 patients during a voiding cystourogram-procedure. The Resistive Index (RI) of each flow curve, reflecting intrarenal flow resistance, was calculated and compared to the mean of four RI measurements taken before contrast media application. Results: One minute after injection of Iopamidol the RI remained unchanged compared to the baseline standard of 0.70. In measurements obtained 2, 3, 4, and 5 minutes after Iopamidol injection a statistically significant rise was seen: (minute 2: 0.74, p < 0.001/minute 3: 0.75, p = 0.001/minute 4: 0.72, p = 0.018/minute 5: 0.74, p = 0.031). During the further course, the resistive indices decreased progressively and showed no significant difference in comparison with the baseline standard value. Conclusion: Color coded duplex sonography is a simple method to detect changes in renal flow resistance after application of radiocontrast media. Based on our results, we believe that the analysis of intrarenal arterial doppler flow profiles constitutes an ideal method to investigate pathophysiologic mechanisms of radiocontrast media-induced nephrotoxicity, as well as pharmacological concepts in nephroprotectivity.
Introduction
Nephrotoxicity of radiocontrast media remains an important clinical issue even after the development of low-osmolar, nonionic substances Citation[1-2]. The underlying pathophysiology is complex and some details thereof remain unsolved. Besides tubulotoxicity Citation[3-4], changes in intrarenal hemodynamics are believed to be of crucial importance. Animal models have suggested that radio-contrast media lead to an increase in vascular resistance, with a subsequent decrease of renal plasma flow and glomerular filtration rate, after an initial and short phase of intrarenal vasodilatation Citation[5-8]. Aside from a few studies in men yielding various different results Citation[9-12], most of the facts known so far are based on animal or in vitro studies. In the current study we investigated whether color-coded duplex ultrasound is an appropriate method to document changes in intrarenal hemodynamics, after intravenous injection of the low-osmolar contrast material Iopamidol.
Methods
During a voiding cystourogram procedure, 10 patients (three female, seven male, average age 51 years) were examined by color-coded duplex ultrasound, with monitoring of intrarenal doppler signals before and after intravenous injection of Iopamidol. The patients had normal renal function, or, as in two cases, slightly impaired function with a maximum creatinine level of 1.4 mg/dL. Three patients were on antihypertensive therapy with a delayed-release nifedipine medication. No patient had theophylline, which is known to interfere with contrast media-induced vasomotor changes, in their drug regimen.
A real time/color-coded duplex scanner (P 700, Philips Medical Technology, Hamburg, Germany) was used by an experienced examiner, with the imaging and doppler systems operated at 3.5 mHz. The patients were examined in a supine position using a lateral or posterolateral approach. Based on an initial B-mode examination, all patients showed at least one morphologically inconspicuous kidney which was then further examined by duplex sonography. Under imaging guidance of the color signal, the sample doppler volume (3 mm) was directed toward an interlobar 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 (see ). Before injection of Iopamidol, four measurements, each one minute apart, were attained, and an average value defined as a baseline standard was calculated for comparison with the RI attained after i.v. application of Iopamidol.
Figure 1. Intrarenal Doppler Flow Spectrum: Calculation of Resistive Index (RI).
After the bolus i.v. injection of 100 mL Iopamidol (Solutrast 300, Byk Gulden, Konstanz, Germany) 10 measurements, each one minute apart (radiography permitting; an average of 7.6 measurements were actually obtained over a 10 minute period in all patients) were performed. A final measurement was obtained 15 minutes post-Iopamidol injection. Along with the ultrasound measurements, blood pressure monitoring by the Riva-Rocci method was performed. No significant changes in blood pressure during or after contrast-media administration were noted in comparison to the baseline values.
Statistical calculations were performed with the aid of SPSS-Systems (SPSS GmbH, Munich, Germany). A p < 0.05 was considered statistically significant. The comparison of the consecutive resistive indices after injection of Iopamidol to the baseline standard prior to i.v. contrast application was calculated by two-tailed-t-test for paired samples.
Results
shows the result of the doppler-sonographic measurements. Heart rates were calculated from the doppler spectra. The four measurements taken prior to Iopamidol injection were constant with a good correlation (r = 0.96) and led to a mean RI of 0.70 (SD ± 0.08) for all patients, which served as the baseline standard.
Table 1. Heart Rate and Intrarenal Resisitive Indices After Injection of 100 mL Iopamidol
One minute after the intravenous application of 100 mL Iopamidol the mean RI was 0.71 (SD ± 0.08) without a statistical difference to the baseline standard. In measurements obtained 2, 3, 4, and 5 minutes after Iopamidol injection a statistically significant change was seen: second minute: RI = 0.74 (SD ± 0.08); p < 0.001; third minute: RI = 0.75 (SD ± 0.07); p = 0.001; fourth minute: RI = 0.72 (SD ± 0.08); p = 0.018; fifth minute: RI = 0.74 (SD ± 0.09); p = 0.031.
During the further course the values decreased progressively and showed no significant difference in comparison with the baseline standard value ().
Figure 2. Change in resisitive index after injection of 100 mL Iopamidol.
Discussion
The pathogenesis of contrast media-associated nephrotoxicity is not yet fully understood. In addition or possibly subsequent to a tubulotoxic effect Citation[3-4], a change of renal hemodynamics is seen as an important contributing factor. In-vitro studies and animal experiments have shown that after infusion of radio-contrast substances, an initial and short intrarenal vasodilatative phase is followed by a pathologic vasoconstriction, with an increase in intravascular resistance and a subsequent decrease in the renal plasma flow and glomerular filtration rate Citation[5-8].
The duration of this vasoconstriction is suspected to last only a few minutes and was also observed for nonionic, low osmolar contrast agents such as Iopamidol used in our study Citation[[8]]. Various experimental studies suggest that adenosine should be regarded as an important mediator. The effect of an adenosine 1-receptor modulated vasoconstriction of the vas afferens and an adenosine 2-receptor modulated dilatation of the vas efferens leads to a decreased perfusion pressure within the glomeruli Citation[[5]], Citation[13-17]. A pathogenetic role of prostaglandins and endothelin as mediators of the vascular effects is also presumed Citation[18-19].
We were able to show that after intravenous injection of Iopamidol, a significant change in intrarenal arterial flow profiles can be documented by duplex-sonography. After the second minute following Iopamidol injection, a significant rise of the calculated resistive indices was temporarily seen, followed by a return to preinjection values shortly thereafter. These findings point to an acute change in intrarenal flow resistance, probably leading to a decreased perfusion after Iopamidol application. A decreasing heart rate, which is another possible explanation for increased resistive indices Citation[[20]], can be excluded ().
Our finding of increased resistive indices over several minutes is consistent with experimental data dealing with intrarenal hemodynamics after contrast media application Citation[5-8]. We therefore see duplex sonography as a feasible and noninvasive method to determine a key pathophysiologic factor of radio contrast media-associated nephrotoxicity.
The few number of studies dealing with hemodynamic changes after contrast media application performed on humans thus far have yielded various results. Weisberg et al. Citation[[12]], Citation[[21]] observed no significant changes in renal venous flow measured by a thermodilution catheter after contrast media injection. Other authors have reported the contrary after measuring paraamino-hippurat clearance Citation[22-23]. A restriction should be noted concerning the first study mentioned above: 75% of the patients in this study received calcium antagonists at the time of the study, which might have protective effects Citation[[11]], Citation[[24]]. In addition, some of the patients did show a decrease in blood flow when compared with values prior to contrast application.
Systematic errors arising from the calculation of paraamino-hippurat clearance cannot be excluded, since the tubular transport of paraamino-hippurat can be influenced by radio contrast media Citation[25-26]. We thus believe that the effects of contrast material application on renal hemodynamics has not yet been adequately defined, and that duplex sonography constitutes a new form of describing hemodynamic changes.
Various pharmacological methods for the prevention of radio contrast media-associated nephrotoxicity have been described. These include volume application with saline solutions Citation[[27]], the application of dopamine Citation[[12]], prostaglandin-E1 Citation[[28]], calcium antagonists Citation[[11]], Citation[[24]], magnesium Citation[[29]], or adenosine receptor antagonists Citation[14-17].
The pharmacological properties of these substances suggest a direct or indirect effect upon renal hemodynamics. We expect the procedure used in our study to be appropriate for documenting the substances' effects on intrarenal flow characteristics after contrast media application. Based on our results, we believe that the duplex-sonographic measurement of intrarenal flow profiles after injection of contrast media is easy to use, and is an ideal method of investigating pathophysiologic mechanisms, as well as pharmacological concepts in nephroprotectivity.
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