Although blood flow to the renal cortex is high and oxygen extraction is low, the renal cortex is remarkably susceptible to hypoxia. Because erythropoietin production has been localized mainly to the renal cortex, the aim of this study was to find a common denominator for both the high susceptibility to hypoxia and oxygen sensing within the renal cortex. By direct measurement of oxygen pressure with microcoaxial needle sensors at superficial glomeruli of the in situ kidney of anesthetized Munich-Wistar-Frömter rats, we obtained mean partial pressure of O2 (PO2) values of 46 +/- 13 (SD) mmHg (n = 71). The simultaneously measured systemic PO2 in arterial blood was 90 +/- 8 mmHg (n = 54). Changing the respirator gas from air to pure oxygen enhanced systemic arterial PO2 to 593 +/- 27 mmHg, whereas PO2 at the superficial glomeruli increased only to a mean of 80 +/- 28 mmHg (n = 71). These data suggest significant preglomerular shunting of oxygen within the cortical vasculature, most likely between interlobular vessels, which are arranged in a countercurrent fashion and represent quantitatively the largest contact area between arteries and veins within the renal cortex.

Objective. There is growing concern about the toxic side effects of daily oral cyclophosphamide (CYC) treatment. Intravenous (IV) pulse administration of CYC has been shown to be effective in patients with systemic lupus erythematosus, but contradictory results have been reported in patients with antineutrophil and renal involvement. cytoplasmic antibody (ANCA)-associated vasculitis.significantly lower levels of follicle-stimulating hormone.Conclusion. This randomized study shows that lV CYC administration is an effective therapeutic tool with low toxicity in patients with ANCA-associated vasculitis Methods. The efficacy and toxicity of IV pulse administration of CYC (0.75 gm/m2) versus daily oral CYC treatment (2 mg/kg body weight) were investigated in a prospective, randomized, multicenter study in patients with ANCA-associated vasculitis and renal involvemen t.Results. The cumulative CYC dose was reduced by 57% in patients with IV pulse treatment (n = 22) compared with patients treated with daily oral therapy (n = 25). Patient survival, remission rate, time of remission, relapse rate, and outcome of renal function were not different between the 2 treatment groups.However, the rate of leukopenia (P < 0.01) and severe infections ( P < 0.05 by 1-tailed test) was significantly reduced in the IV pulse group compared with the group receiving daily oral treatment. Moreover, gonadal toxicity was reduced in the IV pulse group, as indicated by

Objective. There is growing concern about the toxic side effects of daily oral cyclophosphamide (CYC) treatment. Intravenous (IV) pulse administration of CYC has been shown to be effective in patients with systemic lupus erythematosus, but contradictory results have been reported in patients with antineutrophil and renal involvement. cytoplasmic antibody (ANCA)-associated vasculitis. significantly lower levels of follicle-stimulating hormone.Conclusion. This randomized study shows that lV CYC administration is an effective therapeutic tool with low toxicity in patients with ANCA-associated vasculitis Methods. The efficacy and toxicity of IV pulse administration of CYC (0.75 gm/m2) versus daily oral CYC treatment (2 mg/kg body weight) were investigated in a prospective, randomized, multicenter study in patients with ANCA-associated vasculitis and renal involvemen t.Results. The cumulative CYC dose was reduced by 57% in patients with IV pulse treatment (n = 22) compared with patients treated with daily oral therapy (n = 25). Patient survival, remission rate, time of remission, relapse rate, and outcome of renal function were not different between the 2 treatment groups.However, the rate of leukopenia (P < 0.01) and severe infections ( P < 0.05 by 1-tailed test) was significantly reduced in the IV pulse group compared with the group receiving daily oral treatment. Moreover, gonadal toxicity was reduced in the IV pulse group, as indicated by

Glomerular albumin filtration was investigated in the isolated perfused rat kidney and compared with in vivo experiments. Applying micropuncture techniques, we obtained samples from the glomerulus or adjacent early proximal convoluted tubules (EPT) of cortical nephrons and analyzed them for albumin using ultramicrodisc electrophoresis. By determining albumin in glomerular filtrate, we could calculate the sieving coefficient (EPTalb/Palb) directly. The control in vivo value was 0.27 +/- 0.05 X 10(-3) (N = 11). In the isolated perfused rat kidney, the sieving coefficient was 2.1 +/- 0.8 X 10(-3), N = 18 (30 g/liter albumin in perfusate) and 2.3 +/- 0.8 X 10(-3), N = 13 (50 g/liter albumin in perfusate), which is approximately eight times the control in vivo value. With elevated renal venous pressure (20 cm H2O), it increased further to 5.4 +/- 1.6 X 10(-3), N = 8. In all experiments, GFR and proximal transit times were similar to the in vivo controls. Although no major morphologic changes could be detected in any instance, the albumin filtration was greatly elevated. These data confirm the role of a functional barrier in the prevention of glomerular albumin filtration.