John K. Maesaka

We have compared the efficacy of oral to intravenous iron for the chronic maintenance of iron stores in hemodialysis patients. Fifty-two hemodialysis patients with initial serum ferritin greater than 100 ng/mL and transferrin saturation greater than 15% were randomly assigned to one of two groups: those receiving oral iron therapy (n = 32) and those receiving intravenous iron dextran (100 mg twice weekly) (n = 20). At study completion (4 months), the mean hematocrit was significantly higher in the intravenous group than in the oral iron group (34.4% ± 0.7% v 31.8% ± 0.4%, respectively; P < 0.05), the final mean recombinant human erythropoietin dose was 46% lower in the intravenous iron group than in the oral group (4,050 ± 634 U/treatment v 7,563 ± 378 U/ treatment; P < 0.05), and the mean serum ferritin was significantly higher in the intravenous group than in the oral iron group (753.9 ± 30.2 ng/mL v 157.3 ± 15.4 ng/mL, respectively; P < 0.05). We have found that administering iron intravenously instead of orally for chronic maintenance iron supplementation in hemodialysis patients resulted in improved erythropoiesis. We hypothesize that most hemodialysis patients have inadequate iron stores for optimal erythropoiesis when currently recommended levels of ferritin and transferrin saturation are used to guide therapy, and that the chronic use of intravenous iron could reduce recombinant human erythropoietin requirements by maximizing iron stores. The improvement in erythropoiesis was accompanied, however, by an increase in iron indices to levels that could be indicative of tissue iron overload. Future studies must be performed to determine whether lower doses of intravenous iron dextran would improve erythropoiesis without causing potential organ iron overload.

Cerebral salt-wasting syndrome (CSWS) has been regarded as a misnomer of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We take the position that CSWS does exist and might be more common than SIADH. Differentiation between groups has been difficult because of overlapping signs, symptoms, and associated diseases. Euvolemia in SIADH and hypovolemia in CSWS may be the only contrasting variables. However, clinical assessment of extracellular volume is accurate in about 50% of these patients. Determination of serum urate and fractional excretion rates of urate can differentiate one group from the other. In both groups, hyponatremia coexists with hypouricemia and increased fractional excretion of urate. When the hyponatremia is corrected by water restriction, hypouricemia and elevated FEurate correct in SIADH but persist in CSWS. Persistent hypouricemia and elevated FEurate were commonly noted with pulmonary and/or intracranial diseases. The absence of intracranial diseases in some patients suggests that renal salt wasting might be a more appropriate term than CSWS. A review of renal/CSWS reveals three studies involving hyponatremic neurosurgical patients who had decreased blood volume, decreased central venous pressure, and inappropriately high urinary sodium concentrations in the majority of them, suggesting that CSWS was more common than SIADH in neurosurgical patients. Evidence for the presence of a plasma natriuretic factor in CSWS is presented.