Background Recent studies have raised concern about the safety of erythropoiesis‐stimulating agents because of evidence of increased risk of hypertension and cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. In the present study, we investigated the effects of recombinant human erythropoietin (EPO) on endothelial function of gluteal subcutaneous resistance arteries isolated from 17 stage 4 patients (estimated glomerular filtration rate 21.9±7.4 mL/min per 1.73 m2) aged 63±13 years. Methods and Results Arteries were mounted on a pressurized myograph. EPO impaired endothelium‐dependent relaxation in a concentration‐dependent manner. The maximal response to acetylcholine with EPO at 1, 10, and 20 IU/mL was reduced by 12%, 34%, and 43%, respectively, compared with the absence of EPO (P<0.001). EPO‐induced endothelial dysfunction was significantly associated with carotid stiffness and history of cardiovascular events. EPO had no effect on norepinephrine‐induced vasoconstriction or sodium nitroprusside–induced relaxation. ABT‐627, an endothelin type A receptor antagonist, and tempol, a superoxide dismutase mimetic, partially reversed the altered endothelial function in the presence of EPO (P<0.01). Increased expression of endothelin‐1 was found in the vessel wall after incubation with EPO. Conclusions EPO alters endothelial function of resistance arteries in CKD patients via a mechanism involving in part oxidative stress and signaling through an endothelin type A receptor. EPO‐induced endothelial dysfunction could contribute to deleterious effects of EPO described in large interventional trials.

Sierra, C.; Briet, M.; Edwards, C.; Boutouyrie, P.; Davidman, M.; Bercovitch, D.; Frisch, G.; Nessim, S. J.; Lipman, M. L.; Schiffrin, E. L. Author Information

Recent studies have raised concern about the safety of recombinant human erythropoietin (RhuEPO) because of evidence of an increase in the risk of cardiovascular disease in chronic kidney disease (CKD) patients. In the present study we investigated the effect of RhuEPO on the function of resistance arteries isolated from CKD patients. 19 patients (mean age 63 ± 14 years) with stage 4 CKD (mean eGFR 20 ± 5 mL/min/1.73m2), none treated with RhuEPO, were included. Resistance arteries from gluteal subcutaneous tissue were assessed on a pressurized myograph. Endothelium-dependent and independent relaxations were tested with acetylcholine and sodium nitroprusside respectively, with RhuEPO (0, 1, 10 and 20 UI/mL). Tempol (10−3 M), a superoxide dismutase mimetic, was used to inhibit oxidative stress. ABT-627 (10−7M) was used as a selective endothelin subtype A receptor antagonist. At 20 UI/mL, RhuEPO had no effect on norepinephrine-induced vasoconstriction (n = 10) nor on sodium nitroprusside-induced relaxation (n = 10). RhuEPO altered endothelium-dependent relaxation in a dose-dependent manner (maximal relaxation with RhuEPO at 0, 1, 10, 20 UI/ mL, 77.7 ± 3.5

Pharmacologic doses of folic acid are commonly used to reduce the hyperhomocysteinemia of end-stage renal disease (ESRD). Vitamin Bla acts at the same metabolic locus as folic acid, but information is lacking about the specific effects of high doses of this vitamin on homocysteine levels in renal failure. We therefore compared the plasma homocysteine concentrations of maintenance hemodialysis patients in two McGill University-affiliate urban tertiary-care medical centers that differed in the use of vitamin Bla and folic acid therapy. Patients in the first hemodialysis unit are routinely prescribed high-dose folic acid (HI-F, 6 mg/d), whereas those in the second unit receive high-dose vitamin B-12 in the form of a monthly 1-mg intravenous injection, along with conventional oral folic acid (HI-B-12, 1 mg/d). Predialysis homocysteine was 23.4 +/- 6.8 mu mol/L (mean +/- SD) in the HI-F unit and 18.2 +/- 6.1 mu mol/L in the HI-B-12 unit (P < .002), Postdialysis homocysteine was 14.5 +/- 4.1 in the HI-F unit and 10.6 +/- 3.4 mu mol/L in the HI-B-12 unit (P = ,0001). Multiple regression analysis indicated that high-dose parenteral vitamin B-12 was associated with a lower homocysteine concentration even after controlling for the potential confounders of sex, serum urea, serum creatinine, urea reduction ratio, and plasma cysteine. Because this was a cross-sectional observational study, we cannot exclude the possibility that unidentified factors, rather than the different vitamin therapies, account for the different homocysteine levels in the two units. Careful prospective studies of the homocysteine-lowering effect of high-dose parenteral vitamin B-12 in ESRD should be undertaken. Copyright (C) 2000 by W.B, Saunders Company.

Two cases of atypical anaphylactoid reactions to intravenous iron dextran in hemodialysis patients are described. Anaphylactic reactions to iron dextran in dialysis patients are not uncommon. Pulmonary edema is not generally seen in anaphylaxis. Our patients both developed significant pulmonary edema following intravenous infusion of iron dextran, which responded promptly to treatment of anaphylaxis. Potential mechanisms are discussed.

Hadjipavlou, A; Lander, P; Begin, L; Bercovitch, D; Davidman, M; Jakab, E Author Information

Six patients with varying degrees of renal insufficiency developed severe hyperkalemia following hepatic necrosis. The hyperkalemia was seen prior to or concomitant with marked elevations in hepatic enzymes. The basis of the liver disease appeared to involve congestive heart failure and/or hypotension. Necrotic liver cells released intracellular potassium into the blood of patients who were unable to handle the additional potassium load because of renal insufficiency and metabolic acidosis. Furthermore, a shift of potassium into the intracellular space is impaired in uremics by defective Na-K ATPase activity, possibly induced by uremic toxins. The 3 diabetic patients in our series may additionally have had aldosterone deficiency leading to impaired cellular potassium uptake.