Michael H. Schwenk

Ferumoxytol: A New Intravenous Iron Preparation for the Treatment of Iron Deficiency Anemia in Patients with Chronic Kidney Disease

Ferumoxytol is an intravenous iron preparation for treatment of the anemia of chronic kidney disease (CKD). It is a carbohydrate‐coated, superparamagnetic iron oxide nanoparticle. Because little free iron is present in the preparation, doses of 510 mg have been administered safely in as little as 17 seconds. Two prospective, randomized studies compared two doses of ferumoxytol 510 mg given in 5 ± 3 days with 3 weeks of oral iron 200 mg/day (as ferrous fumarate) in anemic patients with CKD. One study enrolled 304 patients with stages 1–5 CKD (predialysis), and the other study enrolled 230 patients with stage 5D CKD (undergoing hemodialysis). In both studies, a greater increase in hemoglobin level from baseline to end of study (day 35) was noted in patients who received ferumoxytol compared with those who received oral iron (mean ± SD 0.82 ± 1.24 vs 0.16 ± 1.02 g/dl in patients with stages 1–5 CKD and 1.02 ± 1.13 vs 0.46 ± 1.06 g/dl in patients with stage 5D CKD, p<0.001). A greater proportion of both predialysis and hemodialysis patients who received ferumoxytol had hemoglobin level increases from baseline of 1 g/dl or more compared with those who received oral iron (p<0.001). In a prospective, double‐blind, crossover study of more than 700 patients with CKD stages 1‐5D that compared the safety of ferumoxytol with normal saline injection, the rates of treatment‐related adverse events were 5.2% and 4.5%, respectively. Serious treatment‐related adverse events were seen in one patient in each treatment group. The most common adverse events with ferumoxytol occurred at the injection site (bruising, pain, swelling, erythema). Dizziness, nausea, pruritus, headache, and fatigue occurred in less than 2% of patients receiving ferumoxytol, with a similar frequency noted after administration of normal saline. In short‐term studies, intravenous ferumoxytol was safely and rapidly administered, and was more effective than oral iron therapy in increasing hemoglobin levels in anemic patients with CKD. Long‐term clinical trials with clinical outcomes and studies comparing ferumoxytol with other parenteral iron agents will help define the role of ferumoxytol in treating the anemia of CKD.

Safety of Iron Sucrose in Hemodialysis Patients Intolerant to Other Parenteral Iron Products

Background/Aims: This report summarizes the data gathered in four prospective studies of intravenous iron sucrose therapy administered to iron-deficient hemodialysis patients with a history of intolerance to other parenteral iron preparations. Methods: A total of 130 iron dextran- and/or sodium ferric gluconate-sensitive patients received intravenous iron sucrose therapy to correct iron deficiency, and/or maintain body iron stores. A history of intolerance to iron dextran alone was reported in 109 patients, to ferric sodium gluconate alone in 6 patients, and to both iron dextran and ferric sodium gluconate in 15 patients. Therapy with iron sucrose consisted of 100- or 200-mg doses administered undiluted intravenously over 2–5 min, or diluted in normal saline and infused over 15–30 min. Test doses of iron sucrose were not administered. The median cumulative dose was 1,000 mg, with a range of 100–5,000 mg. Results: There were no serious adverse events related to iron sucrose therapy in the 130 patients intolerant to other iron preparations. There were 14 nonserious drug-related adverse events in 8 patients attributed to iron sucrose, none of which resulted in discontinuation of therapy. These events were classified as either of severe (diarrhea), moderate (hypotension, nausea, vomiting), or mild severity (constipation, dry mouth, skin irritation). Conclusion: Iron sucrose therapy is safe and well tolerated in hemodialysis patients intolerant to iron dextran and/or sodium ferric gluconate.

Effect of Angiotensin-Converting Enzyme Inhibitors on Response to Erythropoietin Therapy in Chronic Dialysis Patients

Background: Erythropoietin (EPO) therapy is a common and effective treatment for the correction of anemia in patients with end-stage renal disease. Simultaneous treatment with angiotensin-converting enzyme (ACE) inhibitors for the control of hypertension and/or heart failure is often necessary. Recent reports in the literature have raised concern about a potential interaction between these drugs, with a resultant decreased EPO efficacy. Methods: To investigate whether this interaction occurs in chronic dialysis patients, we retrospectively reviewed the records of 175 patients receiving chronic dialysis. All study patients were treated with EPO for at least 3 months, and had normal iron indices. Patients were treated with ACE inhibitors for at least 3 months, at a constant daily dose for at least 1 month (group 1, n = 32), or did not receive ACE inhibitors (group 2, n = 143). Patients with infections or overt iron deficiency were excluded. Total weekly EPO doses and hematocrit (Hct)/hemoglobin (Hgb) values in the two groups were compared. Variables known to affect response to EPO were compared, including ferritin, transferrin saturation, dialysis dose and serum aluminum. Results: Total weekly EPO dose was 17,358 ± 6,871 units in group 1 and 17,612 ± 7,744 units in group 2 (p = 0.854). The achieved Hct was 32.1 ± 4.4% (group 1) and 30.5 ± 4.0% (group 2) (p = 0.079). Similarly, Hgb, ferritin, transferrin saturation, Kt/V, and serum aluminum were not different. The dose or duration of ACE inhibitor therapy did not affect Hgb or Hct. Thus, ACE inhibitor therapy does not appear to affect response to EPO in chronic dialysis patients.

New empiric expressions to calculate single pool Kt/V and equilibriated Kt/V

Most formulae used for Kt/V computations are cumbersome and require variables that are not always available. Even the simplest models involve urea distribution volume or patient postdialysis weight. Calculating urea reduction ratio (URR) is easier and does not require additional variables, but it fails to account for residual renal function or for the removal of urea when urea levels do not change, e.g., during ultrafiltration. The goal of this study was to derive new expressions to calculate Kt/V based on URR using bivariate and multivariate linear and nonlinear models, with the URR adjusted for ultrafiltration volume and time on dialysis. Models were derived from a database of 598 dialysis records with a mean spKt/V of 1.6 (range 0.74–2.8). Models were validated on the same dataset that they were derived from and a separate dataset consisting of 17,190 dialysis records. The validation was made by comparing the empirically derived models with the Gotch and Daugirdas formulae. Among our empirically derived expressions, the closest approximation of the “gold standard,” Kt/V, is the multivariate linear model of URR adjusted for ultrafiltration volume. When information about ultrafiltration is not available, the bivariate exponential formula can be successfully used to estimate Kt/V.