- Email: [email protected]
Effects on renal haemodynamics and tubular function of the contrast medium ioxaglate in renal transplant patients
ClinicalRadiology (1995) 50, 476-478
Effects on Renal Haemodynamics and Tubular Function of the Contrast Medium Ioxaglate in Renal Transplant Patients G. D E R A Y , C. M O U Q U E T , S. O U R H A M A , M. F. B E L L I N , C. J A C Q U I A U D , J. L U C I A N I , M. O. B I T K E R and C. JACOBS
Departments of Nephrology, Urology (Kidney and Pancreas Transplant Unit), Biochemistry and Radiology, H6pital Pitie, Salpetriere, Paris, France The aim of this study was to evaluate the effects of Ioxaglate on renal haemodynamies and tubular function in renal transplant patients at increased risk of nephrotoxicity. 21 patients undergoing either intravenous pyelography or arteriography with Ioxaglate were studied. Renal clearance studies were carried out I day before and 1 day after administration of Ioxaglate (173 • 37 ml) injected into each patient. None experienced any adverse reaction. Mean serum creatinine, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and urinary NAG excretion were unaltered by ioxaglate. No patient suffered a nephrotoxic reaction or acute oliguria that required dialysis as a result of the administration of contrast material. In the subset of seven patients receiving cyclosporine the same results were observed. In the subset of 10 patients with a GFR lower than 60 ml[min before injection of Ioxaglate we also observed no significant change in mean GFR, E R P F and urinary N A G excretion. Only two patients had a transient decrease of GFR of between 10 and 20%. The results of this study show that the ionic, low osmolar contrast medium ioxaglate may be used safely in patients with a renal transplant thus extending previous data obtained in patients with chronic renal failure. Deray, G., Mouquet, C., Ourhama, S., Bell• M.F., Jacquiaud, C., Lucian• J., Bitker, M.O. & Jacobs, C. (1995) ClinicalRadiology 50, 476-478. Effects on Renal Haemodynamics and Tubular Function of the Contrast Medium Ioxaglate in Renal Transplant Patients
Accepted for Publication 13 March 1995
Contrast media nephrotoxicity is an important clinical problem with an incidence of 1% in normal subjects [1], 5.5% in patients with moderate chronic renal failure [1] and more than 50% in patients with severe renal failure [2]. Therapeutic manoeuvers designed to reduce the risk of contrast material induced acute renal failure in m a n thus far have been disappointing. Low-osmolality contrast media (LOCM) were developed to improve the iodine-to osmotic particle ration to 3:1. L O C M have been clearly associated with a lower incidence of minor clinical adverse effects. However their renal tolerance remains controversial. The pathophysiology of contrast media nephrotoxicity most likely involves intrarenal vasoconstriction and direct cellular toxicity [3,4]. Therefore, both tubular function and renal haemodynamics must be evaluated to assess the nephrotoxicity of contrast media. Ioxaglate is an ionic low osmolar contrast medium which is widely used in cardiac angiography. This contrast media has already shown a high level of renal safety in the rat [5] and in patients with chronic renal failure [6]. The aim of this study was to evaluate the effects of Ioxaglate on renal hemodynamics and tubular function in renal transplant patients at increased risk of nephrotoxicity.
Correspondence to: Dr G. Deray, Servicede N6phrologie, H6pital de la Pit• 83, boulevard de l'H6pital, 75013 Paris, France. 9 1995The RoyalCollegeof Radiologists.
P A T I E N T S AND M E T H O D S Twenty-one patients (four females and 17 males) undergoing either intravenous pyelography (n = 18) or arteriography ( n = 3 ) with Ioxaglate (Hexabrix| Guerbet, France) were enrolled in the studyl Their mean age was 45 y e a r s • 13 (range 20 to 63). All patients had a renal transplant and were treated with systemic steroids and azathioprine. Nine patients were concomitantly treated with oral cyclosporine. 173 • 37 ml of Ioxaglate were injected into each patient. Patients with nephrotic syndrome or hepatic failure were excluded. Three patients were diabetic. Serum creatinine levels were stable for at least 5 days before the radiological procedure. N o specific instructions were given regarding prophylactic measures such as diuretics or increased fluid administration intake.
Table 1 - Changesin laboratorydata 24 h after Ioxaglate administration
Serum chemistries (mmol/l)
Before ioxaglate
After ioxaglate
Uric Acid Sodium Potassium Chloride Blood urea Nitrogen Protein Calcium Glucose
289 • 25 138 4- 1 4.5 • 0.1 105 4- 1
269 :k 15 138 -4-1 4.4 • 0.1 106 • 2
11 + 0.9 61 • 2 2.2 :k 0.1 5 • 0.3
10 • 0.8 58 • 1 2.2 • 0.1 5.2 :k 0.5
477
EFFECTS OF IOXAGLATE ON RENAL HAEMODYNAMICS AND TUBULAR FUNCTION
Table 2 - Renal function changes 24 h after administration of loxaglate in 21 renal transplant patients
Serum chemistries
Before loxaglate After loxaglate P value
Serum creatinine (#mol/l) G F R (ml/min) E R P F (ml/min) N A G (mmol/H.molCR)
126 4- 12 65 + 4 342 4- 27 63 4- 10
121 64 366 96
+ 10 4- 4 + 28 4- 15
NS NS NS NS
G F R , glomerular filtration rate; ERPF, effective renal plasma flow; N A G , N-acetyl glucosaminidase. NS, not significant.
The renal clearance studies were carried out 1 day before and 1 day after administration of Ioxaglate. Tests for clearance of inulin (glomerular filtration rate) and p-aminohippuric acid (effective renal plasma flow) were performed according to conventional methods with use of the continuous infusion technique but without catheterization of the bladder. Clearances were determined during three periods, each of 40 rain duration. In addition, a 30 ml sample of fresh urine and a venous blood sample were obtained from all patients 1 day before and 1 day after the procedure to determine serum creatinine, blood urea nitrogen, uric acid, electrolyte levels and urinary N-acetyl glucosamidase (NAG) excretion. Inulin and PAH concentrations were determined using the methods of Galli and Jeanmaire [7]. The N A G activity was measured by the method of Sandman et al. [8]. Results were expressed as mean + SE. Statistical analysis was performed with use of the Number Cruncher Statistical System and paired and unpaired Student's t-tests. Linear regressions were obtained with use of the least squares method. Differences were considered to be significant when P < 0.5. RESULTS The parameters pre- and post-contrast medium showed no significant change (Tables 1 and 2). None of the patients experienced any adverse reaction. Pulse rate, blood pressure, haematologic and serum chemistry values remained stable 24 h after the procedure (Table 1). The mean changes in serum creatinine level, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and urinary NAG excretion are shown in Table 2. Most patients (17 out of 21) had GFR values before contrast medium administration lower than 60ml/min). The range for inulin clearance was 34111 ml/min, and for p-aminohippuric acid clearance 141-624 ml/min. Mean serum creatinine, GFR, ERPF and urinary NAG excretion were unaltered by ioxaglate. No patient
suffered a nephrotoxic reaction or acute oliguria that required dialysis as a result of the administration of contrast material. In the subset of seven patients receiving cyclosporine the same results were observed (Table 3). In the subset of 10 patients with a GFR lower than 60ml/min before injection of Ioxaglate we also did not observe any significant change in mean GFR, ERPF and urinary NAG excretion (Table 3). Only two patients had a transient decrease of GFR of between 10 and 20% (from 34 to 29 and from 70 to 58ml/min). These patients had no other risk factors besides chronic renal failure. No correlation was found between the dose of contrast medium and changes in renal function.
DISCUSSION The results of this study show that the ionic, low osmolar contrast medium ioxaglate may be used safely in patients with a renal transplant, thus extending previous data obtained in patients with chronic renal failure [6] which showed that Ioxaglate has no effect on GFR, ERPF and urinary ~2-microglobulin excretion in subjects with chronic renal failure. Haemodynamic, haematological, rheological and anticoagulant effects of contrast media administration are associated with the degree of osmolality of the contrast agent. Because these effects could lead to adverse reactions, low osmolality contrast media were developed to improve the iodine to osmotic particle ratio to 3 : 1. A major issue concerning the use of new low-osmolar contrast agents is their degree of nephrotoxicity. The results of early experimental studies suggested that use of low-osmolar contrast agents may reduce the frequency of acute renal failure as compared to high osmolar contrast media [4,5,9]. We recently confirmed, in an in vivo model in the rat, that ioxaglate is less nephrotoxic than diatrizoate sodium meglumine (Radioselectan~; Schering, France) [5]. In this model, ioxaglate induced no change in serum creatinine concentration and creatinine clearance. By contrast diatrizoate sodium meglumine induced a sharp decline in gomerular filtation rate 24 h after its administration. Furthermore, in our model, ioxaglate induced a lesser increase in urinary N-acetyl-beta-ghicosaminidase excretion than diatrizoate sodium meglumine, which suggests less direct tubular toxicity. Similarly, at pathological examination, 50% of the kidneys perfused with diatrizoate sodium meglumine showed tubular necrosis whereas no such lesions were observed after Ioxaglate administration. The results of the available studies on the renal
Table 3 - Renal function changes 24 h after administration of Ioxaglate in renal transplant patients receiving cyclosporine and in renal transplant patients with renal insufficiency (GFR < 60 ml/min)
Serum chemistries
G F R (ml/min) E R P F (ml/min) NAG (mmol/H.mmolCR)
Cyclosporine treated patients
Patients with GFR < 60ml/min
Before loxaglate
After loxaglate
Before loxaglate
After loxaglate
P value
60 + 8 316 + 40 40 • 9
57 + 7 350 + 45 47 4- 9
48 • 2 264 + 20 49 + 14
49 + 3 278 + 18 68 • 13
NS NS NS
9 1995 The Royal College of Radiologists, ClinicalRadiology, 50, 476 478.
478
CLINICAL RADIOLOGY
tolerance of iodinated contrast media are conflicting [10-13]. This may be due to the different sensitivity and accuracy of the parameters of renal function that have been used to evaluate nephrotoxicity. In many studies only plasma creatinine or creatinine clearance have been determined which both have only modest reliability. It should be emphasized that serum creatinine levels are maintained until there is a reduction of approximately 50% of G F R [14]. Therefore, plasma creatinine increases only when glomerular filtration rate is markedly impaired. Furthermore, creatinine clearance may be modified in toxic nephropathy; tubular secretion of creatinine is the major cause of overestimation of the true G F R and the contribution of tubular secretion to the overall renal clearance of creatinine is unpredictable and variable. Also it has been shown that tubular secretion increases as renal function decreases and may vary over time. Therefore, in studies such as ours, sensitive indexes are mandatory to evaluate accurately the changes in renal function. Several mechanisms have been proposed to explain the nephrotoxicity of contrast media. These include intra renal vasoconstriction, which may be evaluated with effective renal plasma flow and glomerular filtration rate, and tubular injury reflected by increased activity of tubule specific enzymes eliminated in the urine. Measurement of urinary N A G excretion is a well established means of detecting and monitoring renal damage [15-17]. Only very few studies have evaluated the effects of the different contrast media on both renal haemodynamics and tubular function. In our patients the rise in urinary enzyme concentration was small. Furthermore, ERPF and GF R remained unchanged indicating no major renal haemodynamic disturbances. Interestingly in the subsets of patients with risk factors, i.e. treatment with cyclosporine and/or chronic renal failure (GFR less than 60ml/min), the same renal tolerance of Ioxaglate was observed. Ioxaglate can thus be considered as a safe contrast medium for investigations in high risk patients. Acknowledgements. The authors thank Mrs F. Raymond for technical assistance and Mrs B. Celestin for secretarial assistance. Grant Support: By a grant from the Dred.
REFERENCES
1 Parfrey PS, Grifliths SM, Barnett BJ et al. Contrast materialinduced renal failure in patients with diabetes mellitus, renal insufficiency, or both. New England Journal of Medicine 1989;320: 143-149. 2 Manske CL, Spraska JM, Stony JT et al. Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography. American Journal of Medicine 1990;89:615 620. 3 Spinler SA, Goldfarb S. Nephrotoxicity of contrast media following cardiac angiography: Pathogenesis, clinical course and preventive measures, including the role of low osmolality contrast media. Annals of Pharmacotherapy 1992;26:56-64. 4 Messana JM, Cieslinski DA, Nguyen VD et al. Comparison of the toxicity of the radiocontrast agents, iopamidol and diatrizoate, to rabbit renal proximal tubule cells in vitro. Journal of Pharmacological Experimental Therapy 1988;244:1139-1144. 5 Deray G, Dubois M, Martinez E et al. Radiocontrast nephrotoxicity in rat: A new model of acute renal failure. American Journal of Nephrology 1990;10:507 514. 6 Deray G, Cacoub P, Jacquiaud C et al. Renal tolerance of Ioxaglate in patients with chronic renal failure. Radiology 1991;179:395-397. 7 Galli A, Jeanmaire J. Dosage colorim&ique de Hnuline dans le sang et dans les urines. Applications fi l'analyse automatique. Annales de Biologie Clinique 1965;23:931-941. 8 Bourbouze R. Excretion of urinary N-Acetyl-/3-D-Glucosaminidase isoenzymes after transplantation in the rat. Journal Clinical Chemistry and Clinical Biochemistry 1987;25:71-76. 9 Deray G, Baumelou B, Brillet G e t al. Effects of ischemia on renal vasoconstriction induced by contrast media in the dog. Clinical Nephrology 1991;36:93 97. 10 Schwab SJ, Hlaky MA, Pieper KS et al. A randomized controlled trial of a non-ionic and an ionic radiographic contrast agent. New England Journal of Medicine 1989;320:149 153. 11 Gomes AS, Lois JF, Baker JD et al. Acute renal dysfunction in high-risk patients after angiography: comparison of ionic and non ionic contrast media. Radiology 1989; 170:65-68. 12 Gale ME, Robbins AH, Hamburger RJ et al. Renal toxicity of contrast agents: iopamidal, iothalamate, and diatrizoate. American Journal o f Roentgenology 1984;142:333-335. 13 Denys BG, Reddy SP, Uretsky BF. Nephrotoxicity of a nonionic (iopamidol) versus an ionic (diatrizoate) contrast agent in the patient after cardiac transplant with moderate cyclosporineinduced renal insufficiency. American Journal o f Cardiology 1989; 64:405 406. 14 Levey AS, Madaio MP, Perrone RD. Laboratory assessment of renal disease: clearance, urinalysis and renal biopsy. In: The Kidney, 4th ed. Philadelphia: WB Saunders Co., 1991:919-968. 15 Bourbouze R, Bernard M, Baumann FC et al. Subcellular distribution of the N-Acetyl-B-D-glucosaminidase isoenzymes from rabbit kidney corter. Cellular and Molecular Biology 1984;32:64-74. 16 Meaney RF, Wesintein MA, Buonocore E et al. Digital substraction angiography of the human cardiovascular system. American Journal of Roentgenology 1980;135:1155-1160. 17 Price RG. Urinary enzymes, nephrotoxicity and renal disease. Toxicology 1982;23:99 134.
9 1995 The Royal College of Radiologists, ClinicalRadiology, 50, 476 478.
Effects on Renal Haemodynamics and Tubular Function of the Contrast Medium Ioxaglate in Renal Transplant Patients G. D E R A Y , C. M O U Q U E T , S. O U R H A M A , M. F. B E L L I N , C. J A C Q U I A U D , J. L U C I A N I , M. O. B I T K E R and C. JACOBS
Departments of Nephrology, Urology (Kidney and Pancreas Transplant Unit), Biochemistry and Radiology, H6pital Pitie, Salpetriere, Paris, France The aim of this study was to evaluate the effects of Ioxaglate on renal haemodynamies and tubular function in renal transplant patients at increased risk of nephrotoxicity. 21 patients undergoing either intravenous pyelography or arteriography with Ioxaglate were studied. Renal clearance studies were carried out I day before and 1 day after administration of Ioxaglate (173 • 37 ml) injected into each patient. None experienced any adverse reaction. Mean serum creatinine, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and urinary NAG excretion were unaltered by ioxaglate. No patient suffered a nephrotoxic reaction or acute oliguria that required dialysis as a result of the administration of contrast material. In the subset of seven patients receiving cyclosporine the same results were observed. In the subset of 10 patients with a GFR lower than 60 ml[min before injection of Ioxaglate we also observed no significant change in mean GFR, E R P F and urinary N A G excretion. Only two patients had a transient decrease of GFR of between 10 and 20%. The results of this study show that the ionic, low osmolar contrast medium ioxaglate may be used safely in patients with a renal transplant thus extending previous data obtained in patients with chronic renal failure. Deray, G., Mouquet, C., Ourhama, S., Bell• M.F., Jacquiaud, C., Lucian• J., Bitker, M.O. & Jacobs, C. (1995) ClinicalRadiology 50, 476-478. Effects on Renal Haemodynamics and Tubular Function of the Contrast Medium Ioxaglate in Renal Transplant Patients
Accepted for Publication 13 March 1995
Contrast media nephrotoxicity is an important clinical problem with an incidence of 1% in normal subjects [1], 5.5% in patients with moderate chronic renal failure [1] and more than 50% in patients with severe renal failure [2]. Therapeutic manoeuvers designed to reduce the risk of contrast material induced acute renal failure in m a n thus far have been disappointing. Low-osmolality contrast media (LOCM) were developed to improve the iodine-to osmotic particle ration to 3:1. L O C M have been clearly associated with a lower incidence of minor clinical adverse effects. However their renal tolerance remains controversial. The pathophysiology of contrast media nephrotoxicity most likely involves intrarenal vasoconstriction and direct cellular toxicity [3,4]. Therefore, both tubular function and renal haemodynamics must be evaluated to assess the nephrotoxicity of contrast media. Ioxaglate is an ionic low osmolar contrast medium which is widely used in cardiac angiography. This contrast media has already shown a high level of renal safety in the rat [5] and in patients with chronic renal failure [6]. The aim of this study was to evaluate the effects of Ioxaglate on renal hemodynamics and tubular function in renal transplant patients at increased risk of nephrotoxicity.
Correspondence to: Dr G. Deray, Servicede N6phrologie, H6pital de la Pit• 83, boulevard de l'H6pital, 75013 Paris, France. 9 1995The RoyalCollegeof Radiologists.
P A T I E N T S AND M E T H O D S Twenty-one patients (four females and 17 males) undergoing either intravenous pyelography (n = 18) or arteriography ( n = 3 ) with Ioxaglate (Hexabrix| Guerbet, France) were enrolled in the studyl Their mean age was 45 y e a r s • 13 (range 20 to 63). All patients had a renal transplant and were treated with systemic steroids and azathioprine. Nine patients were concomitantly treated with oral cyclosporine. 173 • 37 ml of Ioxaglate were injected into each patient. Patients with nephrotic syndrome or hepatic failure were excluded. Three patients were diabetic. Serum creatinine levels were stable for at least 5 days before the radiological procedure. N o specific instructions were given regarding prophylactic measures such as diuretics or increased fluid administration intake.
Table 1 - Changesin laboratorydata 24 h after Ioxaglate administration
Serum chemistries (mmol/l)
Before ioxaglate
After ioxaglate
Uric Acid Sodium Potassium Chloride Blood urea Nitrogen Protein Calcium Glucose
289 • 25 138 4- 1 4.5 • 0.1 105 4- 1
269 :k 15 138 -4-1 4.4 • 0.1 106 • 2
11 + 0.9 61 • 2 2.2 :k 0.1 5 • 0.3
10 • 0.8 58 • 1 2.2 • 0.1 5.2 :k 0.5
477
EFFECTS OF IOXAGLATE ON RENAL HAEMODYNAMICS AND TUBULAR FUNCTION
Table 2 - Renal function changes 24 h after administration of loxaglate in 21 renal transplant patients
Serum chemistries
Before loxaglate After loxaglate P value
Serum creatinine (#mol/l) G F R (ml/min) E R P F (ml/min) N A G (mmol/H.molCR)
126 4- 12 65 + 4 342 4- 27 63 4- 10
121 64 366 96
+ 10 4- 4 + 28 4- 15
NS NS NS NS
G F R , glomerular filtration rate; ERPF, effective renal plasma flow; N A G , N-acetyl glucosaminidase. NS, not significant.
The renal clearance studies were carried out 1 day before and 1 day after administration of Ioxaglate. Tests for clearance of inulin (glomerular filtration rate) and p-aminohippuric acid (effective renal plasma flow) were performed according to conventional methods with use of the continuous infusion technique but without catheterization of the bladder. Clearances were determined during three periods, each of 40 rain duration. In addition, a 30 ml sample of fresh urine and a venous blood sample were obtained from all patients 1 day before and 1 day after the procedure to determine serum creatinine, blood urea nitrogen, uric acid, electrolyte levels and urinary N-acetyl glucosamidase (NAG) excretion. Inulin and PAH concentrations were determined using the methods of Galli and Jeanmaire [7]. The N A G activity was measured by the method of Sandman et al. [8]. Results were expressed as mean + SE. Statistical analysis was performed with use of the Number Cruncher Statistical System and paired and unpaired Student's t-tests. Linear regressions were obtained with use of the least squares method. Differences were considered to be significant when P < 0.5. RESULTS The parameters pre- and post-contrast medium showed no significant change (Tables 1 and 2). None of the patients experienced any adverse reaction. Pulse rate, blood pressure, haematologic and serum chemistry values remained stable 24 h after the procedure (Table 1). The mean changes in serum creatinine level, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and urinary NAG excretion are shown in Table 2. Most patients (17 out of 21) had GFR values before contrast medium administration lower than 60ml/min). The range for inulin clearance was 34111 ml/min, and for p-aminohippuric acid clearance 141-624 ml/min. Mean serum creatinine, GFR, ERPF and urinary NAG excretion were unaltered by ioxaglate. No patient
suffered a nephrotoxic reaction or acute oliguria that required dialysis as a result of the administration of contrast material. In the subset of seven patients receiving cyclosporine the same results were observed (Table 3). In the subset of 10 patients with a GFR lower than 60ml/min before injection of Ioxaglate we also did not observe any significant change in mean GFR, ERPF and urinary NAG excretion (Table 3). Only two patients had a transient decrease of GFR of between 10 and 20% (from 34 to 29 and from 70 to 58ml/min). These patients had no other risk factors besides chronic renal failure. No correlation was found between the dose of contrast medium and changes in renal function.
DISCUSSION The results of this study show that the ionic, low osmolar contrast medium ioxaglate may be used safely in patients with a renal transplant, thus extending previous data obtained in patients with chronic renal failure [6] which showed that Ioxaglate has no effect on GFR, ERPF and urinary ~2-microglobulin excretion in subjects with chronic renal failure. Haemodynamic, haematological, rheological and anticoagulant effects of contrast media administration are associated with the degree of osmolality of the contrast agent. Because these effects could lead to adverse reactions, low osmolality contrast media were developed to improve the iodine to osmotic particle ratio to 3 : 1. A major issue concerning the use of new low-osmolar contrast agents is their degree of nephrotoxicity. The results of early experimental studies suggested that use of low-osmolar contrast agents may reduce the frequency of acute renal failure as compared to high osmolar contrast media [4,5,9]. We recently confirmed, in an in vivo model in the rat, that ioxaglate is less nephrotoxic than diatrizoate sodium meglumine (Radioselectan~; Schering, France) [5]. In this model, ioxaglate induced no change in serum creatinine concentration and creatinine clearance. By contrast diatrizoate sodium meglumine induced a sharp decline in gomerular filtation rate 24 h after its administration. Furthermore, in our model, ioxaglate induced a lesser increase in urinary N-acetyl-beta-ghicosaminidase excretion than diatrizoate sodium meglumine, which suggests less direct tubular toxicity. Similarly, at pathological examination, 50% of the kidneys perfused with diatrizoate sodium meglumine showed tubular necrosis whereas no such lesions were observed after Ioxaglate administration. The results of the available studies on the renal
Table 3 - Renal function changes 24 h after administration of Ioxaglate in renal transplant patients receiving cyclosporine and in renal transplant patients with renal insufficiency (GFR < 60 ml/min)
Serum chemistries
G F R (ml/min) E R P F (ml/min) NAG (mmol/H.mmolCR)
Cyclosporine treated patients
Patients with GFR < 60ml/min
Before loxaglate
After loxaglate
Before loxaglate
After loxaglate
P value
60 + 8 316 + 40 40 • 9
57 + 7 350 + 45 47 4- 9
48 • 2 264 + 20 49 + 14
49 + 3 278 + 18 68 • 13
NS NS NS
9 1995 The Royal College of Radiologists, ClinicalRadiology, 50, 476 478.
478
CLINICAL RADIOLOGY
tolerance of iodinated contrast media are conflicting [10-13]. This may be due to the different sensitivity and accuracy of the parameters of renal function that have been used to evaluate nephrotoxicity. In many studies only plasma creatinine or creatinine clearance have been determined which both have only modest reliability. It should be emphasized that serum creatinine levels are maintained until there is a reduction of approximately 50% of G F R [14]. Therefore, plasma creatinine increases only when glomerular filtration rate is markedly impaired. Furthermore, creatinine clearance may be modified in toxic nephropathy; tubular secretion of creatinine is the major cause of overestimation of the true G F R and the contribution of tubular secretion to the overall renal clearance of creatinine is unpredictable and variable. Also it has been shown that tubular secretion increases as renal function decreases and may vary over time. Therefore, in studies such as ours, sensitive indexes are mandatory to evaluate accurately the changes in renal function. Several mechanisms have been proposed to explain the nephrotoxicity of contrast media. These include intra renal vasoconstriction, which may be evaluated with effective renal plasma flow and glomerular filtration rate, and tubular injury reflected by increased activity of tubule specific enzymes eliminated in the urine. Measurement of urinary N A G excretion is a well established means of detecting and monitoring renal damage [15-17]. Only very few studies have evaluated the effects of the different contrast media on both renal haemodynamics and tubular function. In our patients the rise in urinary enzyme concentration was small. Furthermore, ERPF and GF R remained unchanged indicating no major renal haemodynamic disturbances. Interestingly in the subsets of patients with risk factors, i.e. treatment with cyclosporine and/or chronic renal failure (GFR less than 60ml/min), the same renal tolerance of Ioxaglate was observed. Ioxaglate can thus be considered as a safe contrast medium for investigations in high risk patients. Acknowledgements. The authors thank Mrs F. Raymond for technical assistance and Mrs B. Celestin for secretarial assistance. Grant Support: By a grant from the Dred.
REFERENCES
1 Parfrey PS, Grifliths SM, Barnett BJ et al. Contrast materialinduced renal failure in patients with diabetes mellitus, renal insufficiency, or both. New England Journal of Medicine 1989;320: 143-149. 2 Manske CL, Spraska JM, Stony JT et al. Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography. American Journal of Medicine 1990;89:615 620. 3 Spinler SA, Goldfarb S. Nephrotoxicity of contrast media following cardiac angiography: Pathogenesis, clinical course and preventive measures, including the role of low osmolality contrast media. Annals of Pharmacotherapy 1992;26:56-64. 4 Messana JM, Cieslinski DA, Nguyen VD et al. Comparison of the toxicity of the radiocontrast agents, iopamidol and diatrizoate, to rabbit renal proximal tubule cells in vitro. Journal of Pharmacological Experimental Therapy 1988;244:1139-1144. 5 Deray G, Dubois M, Martinez E et al. Radiocontrast nephrotoxicity in rat: A new model of acute renal failure. American Journal of Nephrology 1990;10:507 514. 6 Deray G, Cacoub P, Jacquiaud C et al. Renal tolerance of Ioxaglate in patients with chronic renal failure. Radiology 1991;179:395-397. 7 Galli A, Jeanmaire J. Dosage colorim&ique de Hnuline dans le sang et dans les urines. Applications fi l'analyse automatique. Annales de Biologie Clinique 1965;23:931-941. 8 Bourbouze R. Excretion of urinary N-Acetyl-/3-D-Glucosaminidase isoenzymes after transplantation in the rat. Journal Clinical Chemistry and Clinical Biochemistry 1987;25:71-76. 9 Deray G, Baumelou B, Brillet G e t al. Effects of ischemia on renal vasoconstriction induced by contrast media in the dog. Clinical Nephrology 1991;36:93 97. 10 Schwab SJ, Hlaky MA, Pieper KS et al. A randomized controlled trial of a non-ionic and an ionic radiographic contrast agent. New England Journal of Medicine 1989;320:149 153. 11 Gomes AS, Lois JF, Baker JD et al. Acute renal dysfunction in high-risk patients after angiography: comparison of ionic and non ionic contrast media. Radiology 1989; 170:65-68. 12 Gale ME, Robbins AH, Hamburger RJ et al. Renal toxicity of contrast agents: iopamidal, iothalamate, and diatrizoate. American Journal o f Roentgenology 1984;142:333-335. 13 Denys BG, Reddy SP, Uretsky BF. Nephrotoxicity of a nonionic (iopamidol) versus an ionic (diatrizoate) contrast agent in the patient after cardiac transplant with moderate cyclosporineinduced renal insufficiency. American Journal o f Cardiology 1989; 64:405 406. 14 Levey AS, Madaio MP, Perrone RD. Laboratory assessment of renal disease: clearance, urinalysis and renal biopsy. In: The Kidney, 4th ed. Philadelphia: WB Saunders Co., 1991:919-968. 15 Bourbouze R, Bernard M, Baumann FC et al. Subcellular distribution of the N-Acetyl-B-D-glucosaminidase isoenzymes from rabbit kidney corter. Cellular and Molecular Biology 1984;32:64-74. 16 Meaney RF, Wesintein MA, Buonocore E et al. Digital substraction angiography of the human cardiovascular system. American Journal of Roentgenology 1980;135:1155-1160. 17 Price RG. Urinary enzymes, nephrotoxicity and renal disease. Toxicology 1982;23:99 134.
9 1995 The Royal College of Radiologists, ClinicalRadiology, 50, 476 478.