icodextrin and Anemia

Dysregulation in total body copper causes severe complications and excess copper can be toxic. Divalent metal transporter 1, duodenal cytochrome B, and copper transporter ATPase7A are included in the many intestinal genes transactivated by HlF-α. On July X, 2022 an 80-year-old female patient on peritoneal dialysis was prescribed roxadustat 100 mg, because darbepoetin was unable to increase hemoglobin level effectively. On the same day, icodextrin 1 L was initiated to mitigate edema. Laboratory data showed hemoglobin 9.1 g/dL, transferrin saturation 77%, copper 123 μg/dL, and iron 170 μg/dL before changing to roxadustat. The patient visited us 6 days after the change because of the appetite loss. Transferrin saturation and serum copper and iron levels increased to 90%, 170 and 203 μg/dL, respectively, which were decreased or normalized after discontinuing roxadustat and icodextrin, suggesting that even short-term roxadustat administration can influence copper levels as well as iron levels. Excess copper and iron levels during roxadustat treatment do not immediately equate with toxicity, but indicate a physiological compensation or transient imbalance of metabolism especially in patients treated with ferric citrate. Further investigation for the hypoxia-inducible factor-prolyl hydroxylase inhibitors effects on iron and copper metabolisms is needed. Determining the short-term effect of roxadustat on serum copper and iron in only this case is impossible. Therefore, further accumulation of similar cases is necessary to clarify the short-term effects of roxadustat on serum copper and iron.

Topics: Aged, 80 and over; Anemia; Copper; Female; Hemoglobins; Humans; Icodextrin; Iron; Peritoneal Dialysis; Transferrins

Although erythropoietin (EPO) derivatives improve anemic status in most end-stage renal disease patients, some EPO-resistant patients remain. Asialo-type EPO is as effective as is native EPO in vitro, but in vivo, it is quickly trapped by the hepatic asialo receptors. Alkaline phosphatase (ALP) also binds to the asialo receptor for degradation. We compared hematologic indices in 27 stable PD patients 1-3 months before and after the start of icodextrin solution. In selected patients, we also performed imaging with 99m-technetium-labeled galactosyl serum albumin (GSA) for asialo receptors. Resistance to EPO was defined as a hematocrit below 30% concurrent with EPO administration of more than 18,000 IU monthly. In 19 patients without EPO resistance started on icodextrin, the average hematocrit level did not change (-1.2%), and the average ALP activity increased 36%. But in 8 patients with EPO resistance, the average hematocrit level increased by 12% (p = 0.03 as compared with baseline), and ALP activity increased by 79% (p = 0.02 as compared to non EPO resistant cases) after icodextrin introduction. In the patients with marked elevation of ALP activity, GSA scintigraphy showed inhibition of tracer binding. These results indicate that improvement in EPO-resistant anemia and greater ALP activity with icodextrin administration are mediated through blockade of the asialo receptors on hepatocytes.

Topics: Alkaline Phosphatase; Anemia; Asialoglycoprotein Receptor; Drug Resistance; Erythropoietin; Glucans; Glucose; Hematocrit; Hemodialysis Solutions; Humans; Icodextrin; Kidney Failure, Chronic; Peritoneal Dialysis; Radiopharmaceuticals; Recombinant Proteins; Technetium Tc 99m Aggregated Albumin; Technetium Tc 99m Pentetate