Renal function and cardiac angiography
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《美国医学杂志》
Department of Pediatric Cardiology and Nephrology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kawaramachi-Hirokoji, Kamikyo-ku Kyoto., Japan
Abstract
Objective : To study the effect of non-ionic contrast medium on renal function in children with cardiovascular disease. Methods : Analysis of renal function in 98 children with cardiovascular disease before and after the use of Iopamidol, Iohexol, and Ioversol was done for angiography. Serum creatinine (s-Cre), urinary N-acetyl-beta-D-glucosaminase (u-NAG), urinary beta 2-microglobulin (u-BMG), and urinary alpha 1-microglobulin (u-AMG) levels were evaluated. Results : Although s-Cre levels remained unchanged, u-NAG/Cre, u-AMG/Cre and u-BMG/Cre significantly increased 12 hours after angiography. Levels of u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre after angiography were significantly higher in neonates and infants (age<12-months, n=32) than in children (age>1-year, n=61), in patients with more than 5 ml/kg of contrast medium (n=25) than in those with less than 5 ml/kg (n=70) and in cyanotic patients (n=13) than in non-cyanotic (n=80) patients. Conclusion : Transient renal tubular dysfunction occurred in all of these three non-ionic contrast mediums. Although renal tubular function was intact on a long-term basis, one should be careful of contrast medium-induced nephropathy, especially in neonates and infants, in patients receiving more than 5ml/kg of contrast mediums in total, and in patients with cyanotic heart disease in using non-ionic contrast mediums.
Keywords: Non-ionic contrast medium; Renal function; Children with cardiovascular disease
Cardiac angiography has been widely used for precise structural and functional diagnoses in children with cardiovascular disease, especially in those with complicated congenital heart disease. One of the major disadvantages of using iodine-based contrast mediums is a risk of renal dysfunction.[1],[2] In adults, some studies showed that an increase in serum creatinine (s-Cre) after angiography was seen in some patients, and the presence of renal insufficiency or diabetes mellitus was associated with an increased risk of contrast medium-induced nephropathy.[1],[2],[3] Recently, large clinical studies have indicated that the use of non-ionic low-osmolar contrast medium substantially reduced the risk of nephropathy in high-risk patients[4],[5],[6],[7], and non-ionic low-osmolar contrast medium is now widely used for cardiac angiography in children. However, the risk of contrast medium-induced nephropathy in children with cardiac disease has not been fully elucidated.[8] Thus, in this study, we analyzed renal function in children with cardiovascular disease after cardiac angiography, using three different non-ionic contrast mediums, i.e., Iopamidol, Iohexol, and Ioversol, to study the safety of using contrast mediums in children with cardiovascular disease.
Materials and Methods
98 patients with cardiovascular disease who had undertaken cardiac catheter and angiography examinations were studied. The contrast medium for each patient was selected randomly from a choice of three different non-ionic contrast mediums: Iopamidol (Iopamiron 370R) 370 mg iodine/ml (n=29), Iohexol (Omunipaque 350R) 350 mg iodine/ml (n=12), and Ioversol (Optiray 350R) 350 mg iodine/ml (n=57). Informed consent for the research protocol was obtained from each patient or parents before cardiac catheterization. S-Cre was measured by enzymatic assays as a parameter for glomerular function. Urinary N-acetyl-beta-D-glucosaminase (u-NAG), urinary beta 2-microglobulin (u-BMG) and urinary alpha 1-microglobulin (u-AMG) were analyzed as parameters for proximal tubular function. These urinary values were standardized with urinary creatinine levels (u-NAG/Cre, u-BMG/Cre ,u-AMG/Cre). U-NAG was assayed by using spectrophotometric assay[9], and u-BMG and u-AMG were measured by Latex agglutination reaction.[10],[11] We measured these parameters at three different time points, i.e., 24 hours before the angiography, and 12 hours and 2 weeks after the angiography. Paired t-test (s-Cre) or Willcoxon signed-ranks test (u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre) were applied to compare the parameters before and after angiography. The differences of parameters between two groups were analyzed by Student's t-test (s-Cre) or Mann-Whitney U test (u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre), and the differences among three groups were analyzed by non-parametric ANOVA. Multiple regression analysis was performed to elucidate the contributions of independent risk factors for renal dysfunction. A statistical significance was defined as p<0.05.
Results
Effect on glomerular and proximal tubular function
We studied 98 children with congenital or acquired heart disease who were undergoing cardiac catheterization, and divided them into three groups: Iopamidol (n=29; median age 1 years, range 5 days ~16 years; median dose of contrast medium 4.4 ml/kg, range 0.7~8.2 ml/kg) , Iohexiol (n=12; median age 1 years, range 15 days ~18 years; median dose of contrast medium 3.1 ml/kg, range 1.7~8.0 ml/kg), and Ioversol (n=57; median age 1 years, range 15 days ~17 years; median dose of contrast medium 4.1 ml/kg, range 0.8~12.7 ml/kg). There were no significant differences in age or in total doses of contrast medium among three patient groups, i.e. patients with Iopamidol, Iohexol, and Ioversol. Before angiography,
s-Cre levels were in normal levels in all patients. Twelve hours after angiography, s-Cre values remained unchanged in all groups table1. Significant increases in u-NAG/Cre, u-BMG/Cre and u-AMG/Cre were noted in all patient groups 12 hours after angiography Figure1. Twelve hours after angiography, u-NAG/Cre, u-BMG/Cre and u-AMG/Cre levels in patients taking Iopamidol were 27.9+/-5.7, 3940.4+/-1728.9 and 21.3+/-8.0 (means +/- SE), respectively. In patients taking Iohexol, these levels were 21.2+/-8.0, 2110.6+/-1293.7 and 6.8+/-1.4, respectively, while in patients taking Ioversol, these were 23.1+/-3.4, 5998.8+/-2821.9, and 17+/-3.4, respectively. Two weeks after angiography, all these parameters returned to pre-angiography levels. Furthermore, among three groups with different contact mediums, there were no significant differences in the values of u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre either before or 12 hours after angiography.
Risk Factors
Next, the risk factors for renal toxicity after angiography in children with cardiovascular disease table2 were examined. In neonates and infants (age < 12 month), u-NAG/Cre and u-BMG/Cre levels in patients less than one year of age before angiography were higher than in those over one year of age. Furthermore, the increase in u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre values 12 hours after angiography was more remarkable in neonate and infants. In patients who were administrated over 5ml/kg of contrast medium, the values of u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre were significantly higher than in those who were administered less than 5ml/kg. U-NAG/Cre levels in patients with cyanotic heart disease before angiography were higher than in patients without cyanosis. And, 12 hours after angiography, u-BMG/Cre and u-AMG/Cre values were higher in patients with cyanosis than in those without cyanosis.
Multiple regression analysis indicated that the effects of age and the existence of cyanosis on u-NAG/Cre levels were evident before angiography, and the effects of age and the dosage of contrast medium on u-NAG/Cre and u-BMG/Cre levels were evident after angiography.
Discussion
In this study, we analyzed several serum and urinary parameters of renal function to clarify the effect of using non-ionic contrast mediums on renal function in children with cardiovascular disease and discussed about the risk factors for contrast medium-induced nephropathy.
The data in this study showed no change in s-Cre levels, and no patients developed contrast medium-induced acute renal failure after angiography. We did not measure GFR and we calculated GFR by Schwartz's formula (data was not shown), but there were no significant reductions of GFR after the injection of contrast mediums.
Measuring u-NAG/Cre, u-BMG/Cre and u-AMG/Cre levels is a non-invasive and useful marker for renal proximal tubular dysfunction. U-BMG and u-AMG are low molecular weight proteins that easily pass through the glomerular basement membrane, and most of them are re-absorbed and catabolized at the proximal tubules.[10],[11] NAG is a lysosomal enzyme, highly concentrated in renal tubular epithelial cells. The urinary excretion rate of NAG is not affected by its serum concentration because NAG is not filtered through the glomerulus.[9] Therefore, the elevations of u-BMG/Cre and u-AMG/Cre represent proximal tubular dysfunction, and an elevation of u-NAG/Cre represent injury to proximal tubules. If proximal tubular epithelial cells are damaged by the contrast medium, NAG, AMG, and BMG are excreted into the urine. In our study, u-NAG/Cre, u-BMG/Cre and u-AMG/Cre were significantly increased in all patient groups 12 hours after angiography. These results indicate that there would be some effects of contrast mediums on tubular function. Histological changes in the contrast medium-induced osmotic nephropathy are characterized by cytoplasmic vacuolization of the proximal tubular epithelial cells.[12] Also, it was reported that this vacuolar response begins within half an hour after the injection of contrast medium, and it lasts for several days.[13] We assume that our results are compatible with these previous reports.
The renal tubular dysfunction induced by contrast mediums was transient, and the values of u-NAG/Cre, u-BMG/Cre and u-AMG/Cre were reduced, 2 weeks after angiography. Thus, we believe that non-ionic contrast mediums, if used within the dosages we have used in this study, could be safely used in children with cardiovascular disease.
In adult patients, it has been proposed that diabetes, pre-existing renal insufficiency, renal hypoperfusion, and high total dose of contrast medium could be one of the risk factors for the nephropathy in the use of contrast mediums.[1],[2] However, the risk factors of renal toxicity in children with cardiovascular disease by using non-ionic contrast medium have not been fully investigated.
It has been reported that u-NAG/Cre and u-BMG/Cre values were high in neonate and age-dependency of these values was evident in healthy children.[14] Again, Kunin CN et al stated that the high u-NAG/Cre value in neonate and infants was due to lowered urinary creatinine excretion or glomerulo-tubular imbalance.[15] Also in the present study, multiple regression analysis showed a significant effect of age on renal tubular function. Furthermore, 12 hours after angiography, the effect of age on renal tubular dysfunction was apparent by multiple regression analysis, and u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre values were significantly higher in neonates and infants than in children over 1 year of age. The high levels of u-NAG/Cre and u-BMG/Cre in patients under one year of age suggest that neonates and infants are susceptible to tubular dysfunction.
Transient proximal tubular dysfunction was also associated with the dose of the contrast medium, i.e., children receiving more than 5ml/kg of contrast medium showed higher levels of renal tubular functional parameters after angiography in this study. Although the tubular dysfunction was transient, the administration of large amounts of contrast medium should be avoided.
Glomerulopathy with proteinuria and renal dysfunction has been described in patients with cyanotic heart anomalies.[8] Histological reports have shown the enlargement of glomerulus with hypercellularity in the mesangium, thickening or destruction of the capillary walls in patients with cyanotic heart anomalies, whereas tubular lesions were rare. In this study, none of the patients with cyanotic heart disease had the elevation of s-Cre after angiography. However, u-BMG/Cre and u-AMG/Cre levels in patients with cyanotic heart disease after angiography were significantly higher compared with those in patients with non-cyanotic disease. So we should be careful for the potential depressive effect of contrast medium on renal tubular function.
Taken together, it would be necessary regarding the fact that contrast medium induce nephrotoxicy within 24 hours of administration. We should avoid using large dose of contrast medium to minimize the incidence of contrast-induced nephropathy, especially in neonates and infants, or patients with cyanotic congenital heart disease.
Conclusion
The results of this study indicate that non-ionic contrast mediums can be safely used for the renal function in children with cardiovascular disease, however we should note that the use of non-ionic contrast mediums leads to transient renal tubular dysfunction. Especially in neonates and infants, in patients receiving more than 5ml/kg of contrast mediums in total, and in patients with cyanotic heart disease, we should be careful for contrast-induced nephropathy.
References
1. Swartz RD, Rubin JE, Leeming BW, Silva P. Renal failure following major angiography. Am J Med 1978; 65: 31-37.
2. Gomes AS, Baker JD, Moore WS. Acute renal dysfunction after major arteriography. Am J Radiol 1985; 145: 1249-1253.
3. Weinrauch LA, Healy RW, Leland OS. Coronary angiography and acute renal failure in diabetic azotemic nephropathy. Ann Intern Med 1977; 86: 56-59.
4. Katholi RE, Taylor GJ, Woodruff RC. Nephrotoxicity of nonionic low-osmolality versus ionic high-osmolality contrast media: A prostective double-blind randomized comparison in human beings. Radiology 1993; 186: 183-187.
5. Taliercio CP, Vliestra RE, Ilstrup DM. A randomized comparison of the nephrotoxicity of iopamidol and diatrizoate in high risk patients undergoing cardiac angiography. J Am Coll Cardiol 1991; 17: 384-390.
6. Lautin EM, Freeman NJ, Schoenfeld AH. Radiocontrast-associated renal dysfunction: A comparison of lower-osmolality and conventional high-osmolality contrast media. AJR 1991; 157: 59-65.
7. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high-and low- osmolality iodinated contrast media. Radiology 1993; 188: 265-270.
8. Dittruch S, Kurschat K, Lange PE. Cyanotic nephropathy and use of non-ionic contrast agents during cardiac catherization in patients with cyanotic congenital heart disease. Cardiol Young 2000; 10: 8-14.
9. Horak E, Hopfer SM, Sunderman FW. Spectrophotometris assay for urinary N-acetyl-beta-D-glucosaminidaseactivity. Clin Chem 1981; 27: 1180-1185.
10. Berggard I, Bearn AG. Isolation and properties of a low molecular weight β 2-microglobilon occuring in human biological fluids. J Biol Chem 1968; 243: 4095-4103.
11. Fanos V, Mussap M, Padovani EM. Evaluation of antibiotic-induced nephrotokicity in preterm neonates by determining urinary alpha-1-microglobulin. Pediatr Nephrol 1996; 10: 645-647.
12. Ansaro Z, Baldwin DS. Acute renal failure due to radio-contrast agents. Nephron 1976; 17: 28-40.
13. Gomes AS, Baker JD, Moore WS. Acute renal dysfunction after major arteriography. AJR 1985; 145: 1249-1253.
14. Nshida M, Kawakatsu H, Komatsu H, Ishiwari K, Tamai M, Tsunamoto K, Kasubushi Y, Sawada T. Values for urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in normal healthy infants. Act Paediatr Jpn 1998; 440: 424-426.
15. Kunin CN, Chesney RW, DeAngelis C. Enzymuria as a maker of renal injury and disease: Studies of N-Acetyl-beta-glucosaminidase in the general population and in patients with renal disease. Pediatrics 1978; 62: 751-761.(Niboshi Ayumi, Nishida Ma)
Abstract
Objective : To study the effect of non-ionic contrast medium on renal function in children with cardiovascular disease. Methods : Analysis of renal function in 98 children with cardiovascular disease before and after the use of Iopamidol, Iohexol, and Ioversol was done for angiography. Serum creatinine (s-Cre), urinary N-acetyl-beta-D-glucosaminase (u-NAG), urinary beta 2-microglobulin (u-BMG), and urinary alpha 1-microglobulin (u-AMG) levels were evaluated. Results : Although s-Cre levels remained unchanged, u-NAG/Cre, u-AMG/Cre and u-BMG/Cre significantly increased 12 hours after angiography. Levels of u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre after angiography were significantly higher in neonates and infants (age<12-months, n=32) than in children (age>1-year, n=61), in patients with more than 5 ml/kg of contrast medium (n=25) than in those with less than 5 ml/kg (n=70) and in cyanotic patients (n=13) than in non-cyanotic (n=80) patients. Conclusion : Transient renal tubular dysfunction occurred in all of these three non-ionic contrast mediums. Although renal tubular function was intact on a long-term basis, one should be careful of contrast medium-induced nephropathy, especially in neonates and infants, in patients receiving more than 5ml/kg of contrast mediums in total, and in patients with cyanotic heart disease in using non-ionic contrast mediums.
Keywords: Non-ionic contrast medium; Renal function; Children with cardiovascular disease
Cardiac angiography has been widely used for precise structural and functional diagnoses in children with cardiovascular disease, especially in those with complicated congenital heart disease. One of the major disadvantages of using iodine-based contrast mediums is a risk of renal dysfunction.[1],[2] In adults, some studies showed that an increase in serum creatinine (s-Cre) after angiography was seen in some patients, and the presence of renal insufficiency or diabetes mellitus was associated with an increased risk of contrast medium-induced nephropathy.[1],[2],[3] Recently, large clinical studies have indicated that the use of non-ionic low-osmolar contrast medium substantially reduced the risk of nephropathy in high-risk patients[4],[5],[6],[7], and non-ionic low-osmolar contrast medium is now widely used for cardiac angiography in children. However, the risk of contrast medium-induced nephropathy in children with cardiac disease has not been fully elucidated.[8] Thus, in this study, we analyzed renal function in children with cardiovascular disease after cardiac angiography, using three different non-ionic contrast mediums, i.e., Iopamidol, Iohexol, and Ioversol, to study the safety of using contrast mediums in children with cardiovascular disease.
Materials and Methods
98 patients with cardiovascular disease who had undertaken cardiac catheter and angiography examinations were studied. The contrast medium for each patient was selected randomly from a choice of three different non-ionic contrast mediums: Iopamidol (Iopamiron 370R) 370 mg iodine/ml (n=29), Iohexol (Omunipaque 350R) 350 mg iodine/ml (n=12), and Ioversol (Optiray 350R) 350 mg iodine/ml (n=57). Informed consent for the research protocol was obtained from each patient or parents before cardiac catheterization. S-Cre was measured by enzymatic assays as a parameter for glomerular function. Urinary N-acetyl-beta-D-glucosaminase (u-NAG), urinary beta 2-microglobulin (u-BMG) and urinary alpha 1-microglobulin (u-AMG) were analyzed as parameters for proximal tubular function. These urinary values were standardized with urinary creatinine levels (u-NAG/Cre, u-BMG/Cre ,u-AMG/Cre). U-NAG was assayed by using spectrophotometric assay[9], and u-BMG and u-AMG were measured by Latex agglutination reaction.[10],[11] We measured these parameters at three different time points, i.e., 24 hours before the angiography, and 12 hours and 2 weeks after the angiography. Paired t-test (s-Cre) or Willcoxon signed-ranks test (u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre) were applied to compare the parameters before and after angiography. The differences of parameters between two groups were analyzed by Student's t-test (s-Cre) or Mann-Whitney U test (u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre), and the differences among three groups were analyzed by non-parametric ANOVA. Multiple regression analysis was performed to elucidate the contributions of independent risk factors for renal dysfunction. A statistical significance was defined as p<0.05.
Results
Effect on glomerular and proximal tubular function
We studied 98 children with congenital or acquired heart disease who were undergoing cardiac catheterization, and divided them into three groups: Iopamidol (n=29; median age 1 years, range 5 days ~16 years; median dose of contrast medium 4.4 ml/kg, range 0.7~8.2 ml/kg) , Iohexiol (n=12; median age 1 years, range 15 days ~18 years; median dose of contrast medium 3.1 ml/kg, range 1.7~8.0 ml/kg), and Ioversol (n=57; median age 1 years, range 15 days ~17 years; median dose of contrast medium 4.1 ml/kg, range 0.8~12.7 ml/kg). There were no significant differences in age or in total doses of contrast medium among three patient groups, i.e. patients with Iopamidol, Iohexol, and Ioversol. Before angiography,
s-Cre levels were in normal levels in all patients. Twelve hours after angiography, s-Cre values remained unchanged in all groups table1. Significant increases in u-NAG/Cre, u-BMG/Cre and u-AMG/Cre were noted in all patient groups 12 hours after angiography Figure1. Twelve hours after angiography, u-NAG/Cre, u-BMG/Cre and u-AMG/Cre levels in patients taking Iopamidol were 27.9+/-5.7, 3940.4+/-1728.9 and 21.3+/-8.0 (means +/- SE), respectively. In patients taking Iohexol, these levels were 21.2+/-8.0, 2110.6+/-1293.7 and 6.8+/-1.4, respectively, while in patients taking Ioversol, these were 23.1+/-3.4, 5998.8+/-2821.9, and 17+/-3.4, respectively. Two weeks after angiography, all these parameters returned to pre-angiography levels. Furthermore, among three groups with different contact mediums, there were no significant differences in the values of u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre either before or 12 hours after angiography.
Risk Factors
Next, the risk factors for renal toxicity after angiography in children with cardiovascular disease table2 were examined. In neonates and infants (age < 12 month), u-NAG/Cre and u-BMG/Cre levels in patients less than one year of age before angiography were higher than in those over one year of age. Furthermore, the increase in u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre values 12 hours after angiography was more remarkable in neonate and infants. In patients who were administrated over 5ml/kg of contrast medium, the values of u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre were significantly higher than in those who were administered less than 5ml/kg. U-NAG/Cre levels in patients with cyanotic heart disease before angiography were higher than in patients without cyanosis. And, 12 hours after angiography, u-BMG/Cre and u-AMG/Cre values were higher in patients with cyanosis than in those without cyanosis.
Multiple regression analysis indicated that the effects of age and the existence of cyanosis on u-NAG/Cre levels were evident before angiography, and the effects of age and the dosage of contrast medium on u-NAG/Cre and u-BMG/Cre levels were evident after angiography.
Discussion
In this study, we analyzed several serum and urinary parameters of renal function to clarify the effect of using non-ionic contrast mediums on renal function in children with cardiovascular disease and discussed about the risk factors for contrast medium-induced nephropathy.
The data in this study showed no change in s-Cre levels, and no patients developed contrast medium-induced acute renal failure after angiography. We did not measure GFR and we calculated GFR by Schwartz's formula (data was not shown), but there were no significant reductions of GFR after the injection of contrast mediums.
Measuring u-NAG/Cre, u-BMG/Cre and u-AMG/Cre levels is a non-invasive and useful marker for renal proximal tubular dysfunction. U-BMG and u-AMG are low molecular weight proteins that easily pass through the glomerular basement membrane, and most of them are re-absorbed and catabolized at the proximal tubules.[10],[11] NAG is a lysosomal enzyme, highly concentrated in renal tubular epithelial cells. The urinary excretion rate of NAG is not affected by its serum concentration because NAG is not filtered through the glomerulus.[9] Therefore, the elevations of u-BMG/Cre and u-AMG/Cre represent proximal tubular dysfunction, and an elevation of u-NAG/Cre represent injury to proximal tubules. If proximal tubular epithelial cells are damaged by the contrast medium, NAG, AMG, and BMG are excreted into the urine. In our study, u-NAG/Cre, u-BMG/Cre and u-AMG/Cre were significantly increased in all patient groups 12 hours after angiography. These results indicate that there would be some effects of contrast mediums on tubular function. Histological changes in the contrast medium-induced osmotic nephropathy are characterized by cytoplasmic vacuolization of the proximal tubular epithelial cells.[12] Also, it was reported that this vacuolar response begins within half an hour after the injection of contrast medium, and it lasts for several days.[13] We assume that our results are compatible with these previous reports.
The renal tubular dysfunction induced by contrast mediums was transient, and the values of u-NAG/Cre, u-BMG/Cre and u-AMG/Cre were reduced, 2 weeks after angiography. Thus, we believe that non-ionic contrast mediums, if used within the dosages we have used in this study, could be safely used in children with cardiovascular disease.
In adult patients, it has been proposed that diabetes, pre-existing renal insufficiency, renal hypoperfusion, and high total dose of contrast medium could be one of the risk factors for the nephropathy in the use of contrast mediums.[1],[2] However, the risk factors of renal toxicity in children with cardiovascular disease by using non-ionic contrast medium have not been fully investigated.
It has been reported that u-NAG/Cre and u-BMG/Cre values were high in neonate and age-dependency of these values was evident in healthy children.[14] Again, Kunin CN et al stated that the high u-NAG/Cre value in neonate and infants was due to lowered urinary creatinine excretion or glomerulo-tubular imbalance.[15] Also in the present study, multiple regression analysis showed a significant effect of age on renal tubular function. Furthermore, 12 hours after angiography, the effect of age on renal tubular dysfunction was apparent by multiple regression analysis, and u-NAG/Cre, u-BMG/Cre, and u-AMG/Cre values were significantly higher in neonates and infants than in children over 1 year of age. The high levels of u-NAG/Cre and u-BMG/Cre in patients under one year of age suggest that neonates and infants are susceptible to tubular dysfunction.
Transient proximal tubular dysfunction was also associated with the dose of the contrast medium, i.e., children receiving more than 5ml/kg of contrast medium showed higher levels of renal tubular functional parameters after angiography in this study. Although the tubular dysfunction was transient, the administration of large amounts of contrast medium should be avoided.
Glomerulopathy with proteinuria and renal dysfunction has been described in patients with cyanotic heart anomalies.[8] Histological reports have shown the enlargement of glomerulus with hypercellularity in the mesangium, thickening or destruction of the capillary walls in patients with cyanotic heart anomalies, whereas tubular lesions were rare. In this study, none of the patients with cyanotic heart disease had the elevation of s-Cre after angiography. However, u-BMG/Cre and u-AMG/Cre levels in patients with cyanotic heart disease after angiography were significantly higher compared with those in patients with non-cyanotic disease. So we should be careful for the potential depressive effect of contrast medium on renal tubular function.
Taken together, it would be necessary regarding the fact that contrast medium induce nephrotoxicy within 24 hours of administration. We should avoid using large dose of contrast medium to minimize the incidence of contrast-induced nephropathy, especially in neonates and infants, or patients with cyanotic congenital heart disease.
Conclusion
The results of this study indicate that non-ionic contrast mediums can be safely used for the renal function in children with cardiovascular disease, however we should note that the use of non-ionic contrast mediums leads to transient renal tubular dysfunction. Especially in neonates and infants, in patients receiving more than 5ml/kg of contrast mediums in total, and in patients with cyanotic heart disease, we should be careful for contrast-induced nephropathy.
References
1. Swartz RD, Rubin JE, Leeming BW, Silva P. Renal failure following major angiography. Am J Med 1978; 65: 31-37.
2. Gomes AS, Baker JD, Moore WS. Acute renal dysfunction after major arteriography. Am J Radiol 1985; 145: 1249-1253.
3. Weinrauch LA, Healy RW, Leland OS. Coronary angiography and acute renal failure in diabetic azotemic nephropathy. Ann Intern Med 1977; 86: 56-59.
4. Katholi RE, Taylor GJ, Woodruff RC. Nephrotoxicity of nonionic low-osmolality versus ionic high-osmolality contrast media: A prostective double-blind randomized comparison in human beings. Radiology 1993; 186: 183-187.
5. Taliercio CP, Vliestra RE, Ilstrup DM. A randomized comparison of the nephrotoxicity of iopamidol and diatrizoate in high risk patients undergoing cardiac angiography. J Am Coll Cardiol 1991; 17: 384-390.
6. Lautin EM, Freeman NJ, Schoenfeld AH. Radiocontrast-associated renal dysfunction: A comparison of lower-osmolality and conventional high-osmolality contrast media. AJR 1991; 157: 59-65.
7. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high-and low- osmolality iodinated contrast media. Radiology 1993; 188: 265-270.
8. Dittruch S, Kurschat K, Lange PE. Cyanotic nephropathy and use of non-ionic contrast agents during cardiac catherization in patients with cyanotic congenital heart disease. Cardiol Young 2000; 10: 8-14.
9. Horak E, Hopfer SM, Sunderman FW. Spectrophotometris assay for urinary N-acetyl-beta-D-glucosaminidaseactivity. Clin Chem 1981; 27: 1180-1185.
10. Berggard I, Bearn AG. Isolation and properties of a low molecular weight β 2-microglobilon occuring in human biological fluids. J Biol Chem 1968; 243: 4095-4103.
11. Fanos V, Mussap M, Padovani EM. Evaluation of antibiotic-induced nephrotokicity in preterm neonates by determining urinary alpha-1-microglobulin. Pediatr Nephrol 1996; 10: 645-647.
12. Ansaro Z, Baldwin DS. Acute renal failure due to radio-contrast agents. Nephron 1976; 17: 28-40.
13. Gomes AS, Baker JD, Moore WS. Acute renal dysfunction after major arteriography. AJR 1985; 145: 1249-1253.
14. Nshida M, Kawakatsu H, Komatsu H, Ishiwari K, Tamai M, Tsunamoto K, Kasubushi Y, Sawada T. Values for urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in normal healthy infants. Act Paediatr Jpn 1998; 440: 424-426.
15. Kunin CN, Chesney RW, DeAngelis C. Enzymuria as a maker of renal injury and disease: Studies of N-Acetyl-beta-glucosaminidase in the general population and in patients with renal disease. Pediatrics 1978; 62: 751-761.(Niboshi Ayumi, Nishida Ma)