Erythropoietin enhances recovery after cisplatin-induced acute renal failure in the rat.

BACKGROUND: Erythropoietin (Epo) is a growth factor whose synthesis mainly takes place in the kidney. Epo has been shown to support the growth not only of erythroid progenitor cells but also of certain other cell types. We attempted to establish whether Epo enhances the recovery from acute renal failure induced by cisplatin. METHODS: Sprague-Dawley rats were randomized into three groups. In the cisplatin group, animals received one intraperitoneal injection of cisplatin (6 mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo group, animals received intrapertoneal cisplatin and a daily injection of Epo (100 IU/kg) for 9 days. In the control group, animals received both placebo preparations alone. Para-aminohippuric acid and inulin clearances were determined after 4 and 9 days to evaluate renal blood flow and glomerular filtration rate. In addition, light microscopy and immunohistochemistry examinations were performed, and in situ proliferating cell nuclear antigen (PCNA) staining was done to estimate the degree of renal tubular cell regenerative activity. The potential role of epithelial growth factor (EGF) was evaluated by semi-quantitative assessment of EGF immunostaining. RESULTS: Renal blood flow and glomerular filtration rate decreased significantly in cisplatin and cisplatin+Epo groups versus control group at day 4. However, at day 9, they both were significantly greater in cisplatin+Epo-treated animals than in rats that had received cisplatin alone. Tubular cell regeneration was significantly enhanced at day 4 in cisplatin+Epo group, compared with cisplatin and control groups respectively. EGF immunostaining was not significantly different between the three groups. CONCLUSION: Epo significantly enhanced the rate of recovery from acute renal failure induced by cisplatin. PCNA staining indicated that Epo might act directly via stimulation of tubular cell regeneration.

Renal effects of low and isoosmolar contrast media on renal hemodynamic in a normal and ischemic dog kidney.

RATIONALE AND OBJECTIVES: The authors investigated the comparative effects of a nonionic dimer contrast medium (iodixanol) with an ionic low osmolar contrast media (locm) (ioxaglate) on renal blood in a normal and an ischemic dog kidney. METHODS: Six dogs were studied for two periods. During the first period (the control period) a renal arteriography was performed with either iodixanol (Visipaque) or ioxaglate (Hexabrix) in a randomized order. Twenty minutes after applying a suprarenal clamp just above the right renal artery, two selective intrarenal contrast media administrations were performed at 30-minute intervals in a randomized order (ischemic period). RESULTS: During the control period ioxaglate and iodixanol induced no change in mean arterial blood pressure and pulse rate. The maximum decrease in renal blood flow (rbf) observed with ioxaglate was 19 +/- 4%. The maximum decrease in rbf observed with iodixanol was 51 +/- 16% versus control period (P = 0.05 compared with ioxaglate). During the ischemic period, renal perfusion pressure was 72 +/- 2 mm Hg and 73 +/- 2 mm Hg before iodixanol and ioxaglate administration, respectively (P = NS). Iodixanol induced a 61 +/- 11% decrease in RBF. These changes were significantly higher than those observed with ioxaglate during the control period and with the control ischemic period. Ioxaglate induced a maximum 11 +/- 6% decrease in RBF at 1 min (P < 0.05 versus iodixanol). These modifications were not significantly higher than those observed during the control period. CONCLUSIONS: In this study the authors found that the renal effect of iodixanol are markedly more pronounced than that of ioxaglate. In the setting of ischemia the effects of iodixanol were only slightly enhanced whereas those of ioxaglate were not modified.

Comparative acute nephrotoxicity of FK-506 and ciclosporin in an isolated in situ autoperfused rat kidney model.

The acute hemodynamic effects of ciclosporin A (Cs-A; 40 and 20 mg/kg), FK506 (1.5 and 0.4 mg/kg), and their vehicles were studied in an in situ autoperfused rat kidney model. Cs-A (60 +/- 7 and 66 +/- 5% of the initial value, respectively; p < 0.05 vs. control group) and FK506 (89 +/- 3 and 77 +/- 3% of the initial value respectively; p < 0.05 vs. control group) induced a significant fall in renal blood flow. Cs-A significantly increased the renal vascular resistance, whereas FK506 had no effect. The glomerular filtration rate (inulin clearance) declined significantly in all groups. Cremophore and FK506 vehicle had no hemodynamic effect on the glomerular filtration rate. In our model, FK506 had less vasoactive effects on the renal hemodynamics than Cs-A.