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Radiographic contrast media induced nephropathy: experimental observations and the protective effect of calcium channel blockers

¹Department of Radiology, Rui Jin Hospital, Shanghai Second Medical University, Shanghai, China, ²College of Pharmacy, Shanghai Medical University, Shanghai, China and ³Department of Diagnostic Imaging, Northern General Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield S5 7AU, UK

View larger version (16K): [in a new window]   Figure 1. Effects of different doses of radiographic contrast medium on renal function of rats pre-treated with indomethacin and L-nitroarginine methyl ester (L-NAME). (a) Serum creatinine (Cr) before () and 24 h after () injection of 8 ml kg-1 saline (Group 1, control) or increasing doses of diatrizoate (Group 2, 4 ml kg-1; Group 3, 6 ml kg-1; and Group 4, 8 ml kg-1). Significant increases (*p<0.01) in serum Cr occurred in Groups 3 and 4, but no significant rise occurred in Groups 1 and 2 (n=5 per group). The rise in serum Cr in Group 4 was significantly higher (p<0.05) than in Group 3. (b) Percentage change in Cr clearance from baseline (24 h pre injection) to 24 h post injection with 8 ml kg-1 saline (Group 1, control) or increasing doses of diatrizoate (Group 2, 4 ml kg-1; Group 3, 6 ml kg-1; and Group 4, 8 ml kg-1. Significant decreases (*p<0.01) in Cr clearance occurred in Groups 3 and 4 but no significant change occurred in Groups 1 and 2 (n=5 per group). The decrease in Cr clearance in Group 4 was larger (p<0.05) than in Group 3.

View larger version (21K): [in a new window]   Figure 2. Effects of the high osmolar diatrizoate and low osmolar iopromide on renal function of rats pre-treated with indomethacin and L-nitroarginine methyl ester (L-NAME). (a) Serum creatinine (Cr) before () and 24 h after () injection of either 6 ml kg-1 of diatrizoate (Group 1) or iopromide (Group 2). Significant increases (*p<0.01) in serum Cr occurred in both groups, but the rise in Group 1 was significantly higher (p<0.05) than in Group 2 (n=5 per group). (b) Percentage in Cr clearance from baseline (24 h pre injection) to 24 h post injection of 6 ml kg-1 of diatrizoate (Group 1) or iopromide (Group 2). Significant decreases (*p<0.01) in Cr clearance occurred in both groups, but the reduction in Group 1 was more severe (p<0.05) than in Group 2 (n=5 per group).

View larger version (24K): [in a new window]   Figure 3. Time course of renal function after injection of diatrizoate in rats pre-treated with indomethacin and L-nitroarginine methyl ester (L-NAME). Significant increase (*p<0.01) in serum creatinine (Cr) occurred 24 h after injection of 8 ml kg-1 of diatrizoate. Serum Cr returned to a level comparable with baseline (pre insult) 7 days after the injection of diatrizoate(n=5).

View larger version (20K): [in a new window]   Figure 4. The effect of the calcium antagonist diltiazem in preventing radiographic contrast medium induced-nephropathy in rats pre-treated with indomethacin and L-nitroarginine methyl ester (L-NAME). (a) Serum creatinine(Cr) before () and 24 h after () injection of 6 ml diatrizoate in rats following intraperitoneal injection of either 4 ml of normal saline (Group 1) or diltiazem (Group 2, 2 mg kg-1; Group 3, 6 mg kg-1; or Group 4, 10 mg kg-1). Significant increase (*p<0.01) in serum Cr occurred in Groups 1, 2 and 3 but no significant rise occurred in Group 4 (n=5 per group). Comparison of the percentage rise in serum Cr from baseline between groups was: Group 1>Group 2 (p<0.05), Group 2>Group 3 (p<0.05) and Group 3>Group 4 (p<0.01). (b) Percentage change in Cr clearance from baseline (24 h pre injection) to 24 h post injection of 6 ml diatrizoate in rats with introperitoneal injection of either 4 ml of normal saline (Group 1) or diltiazem (Group 2, 2 mg kg-1; Group 3, 6 mg kg-1; or Group 4, 10 mg kg-1). Significant decreases (*p<0.01) in Cr clearance occurred in all groups (n=5 per group). The smallest reduction occurred in Group 4. The extent of reduction was: Group 2>Group 3 (p<0.01), Group 3>Group 4 (p<0.01). No significant difference was found between Groups 1 and 2.