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.

Rationale and Objectives. The authors evaluated the involvement of nitric oxide and endothelin in radiographic contrast medium-induced changes in renal hemodynamics.Methods. Eleven anesthetized healthy dogs were each studied during three periods. Thirty minutes before the first, second, and third periods, the dogs received I mt per kilogram of body weight of isotonic saline, L-N-nitro-L-arginine-methyl-ester (L-Name, 10 mg/kg intravenously), and L-arginine (500 mg/kg intravenously), respectively. Renal blood how (RBF) and mean arterial blood pressure were continuously monitored. The glomerular filtration rate (GFR) was evaluated by means of polyfructosan clearance.Results. Contrast medium induced a significant (P < .05) decrease in RBF and GFR and a significant (P < .05) increase in urinary endothelin excretion, L-Name enhanced the effect of contrast media on RBF and GFR. L-arginine attenuated the effect of L-Name on the contrast medium-induced reduction of GFR.Conclusion. These findings support the hypothesis that acute contrast medium-induced intrarenal vasoconstriction map involve an imbalance of endothelial vasoactive agents, nitric oxide, and endothelin, and they confirm the involvement of hemodynamic changes in contrast medium-induced nephropathy.

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.

BACKGROUND:Cyclosporin (CsA) is a potent immunosuppressive drug whose main side-effect is nephrotoxicity. In the kidney, CsA induces vasoconstriction with a decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistance (RVR). CsA enhances platelet-activating factor (PAF) synthesis in mesangial cells in vitro. PAF, a secondary mediator of anaphylaxis and inflammation, exhibits vasoactive properties in the kidney similar to those of CsA.METHODS:The in situ autoperfused rat kidney model was used to investigate whether PAF plays a role in the haemodynamic injury induced by CsA.RESULTS:In this model, CsA (40 mg/kg and 20 mg/kg i.v.) induced a significant decrease in RBF and in GFR and an increase in RVR. BN 52021, a potent and specific PAF antagonist (20 mg/kg i.v. bolus dose) induced a significant increase in GFR (137 +/- 32% of initial value, P < 0.05). BN 52021 (20 and 10 mg/kg) also significantly prevented the decline in RBF and GFR induced by CsA.CONCLUSIONS:We have demonstrated that the PAF antagonist BN 52021 can minimize the alteration of renal function induced by CsA.

BACKGROUND:Renal vasoconstriction and systemic hypertension are well-known effects of bolus or short-term endothelin administration. However, the role of endothelin as a circulating hormone remains largely unknown.METHODS:The present study explores the effects of endothelin-3 (ET-3) on renal haemodynamics and systemic blood pressure during a 3-h and a 3-day intravenous infusion in rats. Male Sprague-Dawley (SD) rats were infused with vehicle (group 1) or ET-3 (group 2), 10 ng/kg per min; group 3, 50 ng/kg per min) delivered via osmotic minipumps into the right jugular vein for 3 days. On day 3 after pump implantation, rats were anaesthetized with Inactin and surgically prepared for assessment of mean arterial blood pressure (MABP), renal plasma flow (RPF), glomerular filtration rate (GFR), and renal vascular resistance (RVR). The same parameters were assessed during a 3-h ET-3 infusion study in SD rats (group 4, vehicle; group 5, ET-3, 10 ng/kg per min; group 6, ET-3, 50 ng/kg per min).RESULTS:In 3-day infused rats, ET-3 induced a significant decrease in RPF (-22+/-7% and -26+/-8% for group 2 and group 3 respectively, P<0.05 vs group 1) and an increase in RVR (+40+/-11% for groups 2 and 3; P<0.05 vs group 1); 50 ng/kg per min ET-3 significantly decreased GFR (-17%, P<0.05 vs group 1). MABP was not significantly affected by endothelin infusion. In acute infusion studies a decrease of the same magnitude was seen for the renal haemodynamics values. 50 ng/kg per min ET-3 increased MABP; a systemic effect that disappeared after the 3-day infusion.CONCLUSIONS:This study suggests that intravenously administered ET-3 in the rat has only a transient effect on systemic blood pressure, whereas it induces alterations in renal haemodynamics after both acute and chronic perfusions.

A. Baumelou, MD, Nephrology Unit, La Pitié Hospital, 83 b de l’Hôpital, F-75651 Paris Cédex 13 (France) Dear Sir, Sulfadiazine (Adiazine®) has been extensively used from the mid 1930s, mainly for treating pulmonary infections, till the introduction of penicillin and other modern antibiotics. By that time, numerous cases of acute renal failure due to crystallization of the drug in the urinary collecting system were reported [1–4]. In recent years sulfadiazine has come into utilization again as therapy for toxoplasmosis in patients with AIDS [5, 6]. We report here on 3 patients who developed acute renal failure while being treated with sulfadiazine in our institution during the last year. Case Reports Case No. 1. He was a 44-year-old man with AIDS known since February 1986 and Kaposi sarcoma since December 1986. Toxoplasmosis with right arm monoparesis developed in March 1986 and was treated with sulfadiazine (6 g/day) and pyrimethamine 50 mg/day. At the start of this treatment his serum creatinine concentration was 100 μmol/l. One month later he suffered from intense back pain and became oliguric (500 ml/day). His serum creatinine concentration had increased up to 350 μmol/l. Urinalysis disclosed no infection. Renal ultrasound showed a multitude of small stones in both kidneys. Following intravenous rehydration and alkalinization (2 liters of isotonic sodium bicarbonate and 1 liter of isotonic glucose with 5 g of NaCl and 2 g of KC1 during the first 48 h), serum creatinine concentration came down to 115 μmol/l. Analysis of the stones that were eliminated spontaneously showed them composed of sulfadiazine cristals. Case No. 2 He was a 46-year-old homosexual man with AIDS and Kaposi sarcoma. Therapy was started with sulfadiazine (4 g/day), inter-feron (18 million units/day) and pyrimethamine 50 mg/day for a choroiditis due to toxoplasmosis. Serum creatinine concentration was 79 μmol/l. 21 days after onset of this treatment, the patient complained of intense headache, abdominal pain and hand shaking. The patient was afebrile, normally hydrated, oliguric (500 ml/day) his blood pressure was 120/80 mm Hg. Serum creatinine concentration was 1,551 μmol, sodium, potassium and carbon dioxide concentration were 122, 7.1 and 10 mmol, respectively. A plain abdominal film revealed two symetric kidneys whose size was slightly enlarged. No obstruction of the urinary tract was