Kinetics, Dialysis Systems, and Adequacy Copper deficiency: A common cause of erythropoietin (rHuEPO) resistant anemia in children on hemodialysis (HD)?

Abstract

Copper (CU) deficiency, as reflected by a low serum CU and ceruloplasmin (CER) level, is a rare complication of chronic HD. When present, common clinical manifestations include anemia and neutropenia. Anecdotally, CU deficiency has been linked to the use of sevelamer hydrochloride (SH), a recently introduced phosphate binding agent. The finding of severe CU deficiency and rHuEPO‐resistant anemia in 3 of our patients (pts) prompted a review of our entire pediatric HD population for the frequency of CU deficiency and its possible relationship to SH. An assessment of serum CU was conducted in 17 pts (male‐11; mean age 169.4 + 49.6 mo) who had received HD for 21.5 + 33.9 months. All pts received three 4‐hour HD sessions weekly with mean single‐pool and equilibrated Kt/V values of 2.29 + 2.5 and 1.56 + 0.37, respectively. 14 of 17 (82%) pts had low serum CU levels with a mean value of 69.1 + 38.3 mcG/DL (normal = 85–150 mcG/DL). 9 of 17 (53%) pts had values <60 mcG/DL and 3 pts had values <25 mcG/DL with CER values of 1.2 mg/dL, 0.6 mg/dL, and 1.8 mg/dL, respectively (normal = 24–40 mg/dL). In the latter 3 pts, hemoglobin values fell to 5.4 gm/dL, 5.2 gm/dL, and 9.2 gm/dL despite regular rHuEPO dosing and adequate iron stores and all pts responded to supplemental CU therapy. The mean hemoglobin of the remaining 14 pts was 11.7 + 1.3 gm/dL. Whereas 13 of 14 (93%) CU deficient pts were receiving SH (142.1 + 112.3 mg/kg/d) for 331.0 + 293.6 days at the time of the CU assessment, there was no significant relationship demonstrated between the dose of SH or the duration of SH therapy and the serum CU level. In conclusion, CU deficiency appears to commonly occur in pediatric HD pts with extremely low values associated with profound anemia responsive to CU therapy. While the chronology of CU deficiency and the introduction of SH suggests an association, additional research is necessary to address this issue in a more definitive manner.