title: Oral zinc supplementation reduces the erythropoietin responsiveness index in patients on hemodialysis.
abstract: BACKGROUND
  In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI).
  
  
  METHODS
  Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL).
  
  
  RESULTS
  There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI.
  
  
  CONCLUSIONS
  Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan. kobayashihiroki2@gmail.com.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan. abe.masanori@nihon-u.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan. kokada@med.nihon-u.ac.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Okada
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan. haru_li_huang@yahoo.co.jp.
authors.forename: Ritsukou
authors.initials: R
authors.lastname: Tei
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan. maruyama.noriaki@nihon-u.ac.jp.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Maruyama
authors.affiliation: Department of Nephrology, Meirikai Chuo General Hospital, 3-2-11, Higashijujou, Kita-ku, 114-0001 Tokyo, Japan. kikuchi5308@air.ocn.ne.jp.
authors.forename: Fumito
authors.initials: F
authors.lastname: Kikuchi
authors.affiliation: Department of Nephrology, Keiai Hospital, 3-10-6, Mukaihara, Itabashi-ku, 173-0036 Tokyo, Japan. thiguchi@keiai-hospital.jp.
authors.forename: Terumi
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-chou, Itabashi-ku, Tokyo 173-8610, Japan. souma.masayoshi@nihon-u.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000740:Anemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002336:Carnosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003300:Copper / Q000097:blood; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D000068817:Epoetin Alfa / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004921:Erythropoietin / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D012044:Regression Analysis; D006435:Renal Dialysis / Q000009:adverse effects; D014131:Trace Elements / Q000097:blood / Q000172:deficiency / Q000494:pharmacology / Q000627:therapeutic use; D015032:Zinc / Q000097:blood / Q000172:deficiency / Q000494:pharmacology / Q000627:therapeutic use*; D017967:Zinc Compounds / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D006454:Hemoglobins; D009942:Organometallic Compounds; D014131:Trace Elements; D017967:Zinc Compounds; C061957:polaprezinc; D004921:Erythropoietin; D000068817:Epoetin Alfa; D003300:Copper; D002336:Carnosine; D005293:Ferritins; D007501:Iron; D015032:Zinc
keywords: erythropoiesis stimulating agent; erythropoietin responsiveness index; hemodialysis; renal anemia; zinc deficiency