title: [Secondary hyperparathyroidism and anemia. Effects of a calcimimetic on the control of anemia in chronic hemodialysed patients. Pilot Study].
abstract: The main cause of resistance to erythropoiesis-stimulating agents (ESA) used for treatment of anemia in chronic hemodialysed patients (CHP) is the iron deficiency, absolute or functional. Secondary hyperparathyroidism (SHPT) is a secondary factor of resistance. Indeed, it has been reported in the literature an improvement of anemia parameters after surgical parathyroidectomy (PTX). The objective of this study is to assess in CHP, the impact of the correction of SHPT by a calcimimetic, cinacalcet (CI), (which is considered as a pharmacological PTX) on the response to ESA, measured by the erythropoietin resistance index (ERI). Twenty-two CHP with severe SHPT documented by an intact parathyroid hormone (iPTH) above 800pg/mL were included in this prospective pilot study. Mineral bone metabolism, anemia and nutritional parameters were measured baseline and after 6 months of treatment by CI. The effect on anemia was assessed at the end of study by the ERI, the change in Hb concentration, and the proportion of patients with Hb levels above 11g/dL.
  
  
  RESULTS
  At the end of study there was a significant decrease (M6 vs M0) in iPTH (1302 vs 674pg/mL or -48%, p=0.006), serum calcium (2.39 vs 2.15mmol/L or -10%), serum phosphate (2 vs 1.7mmol/L or -15%), serum calcium-phosphorus product (CaxP) (4.8 vs 3.8mmol(2)/L(2) or - 20% (p<0.05), and the number of patients with CaxP>4.4mmol(2)/L(2) (64 vs 32%, p<0.05). The level of bone alkaline phosphatase remained stable during the study (28 vs 27 IU/L). The Hb levels increased from 11 to 11.4g/dL, as did the proportion of patients whose Hb concentration reached 11g/dL or higher (50 vs 70%, p<0.05) without important change of the median weekly ESA dosis in the majority of patients, 18 cases (81%) vs four (19%). Two subgroups were identified from the median decreases in iPTH (delta iPTH) between M0 and M6, Group 1 (delta iPTH≥400pg/mL, n=10) and group 2 (delta iPTH<400pg/mL, n=12): in group 1, we found a correlation between the decrease in iPTH by CI and the stability or decrease in ERI (group 1), at comparable dose of dialysis, nutritional and iron intakes and inflammatory profiles; in group 2 without a significant effect of CI on PTH reduction the levels of ERI and ESA dosis were more elevated.
  
  
  CONCLUSIONS
  A treatment by calcimimetic improves the control of anemia by ESA in CHP and interferes positively on a cause of secondary resistance to ESA represented by SHPT. The mechanism of these effects could be linked to the decreased of bone marrow fibrosis and inflammation and to the triptych formed by the reduction in iPTH, CaxP and phosphate.
authors.affiliation: Association pour l'utilisation du rein artificiel dans la région lyonnaise (Aural), 124, rue Villon, 69600 Lyon, France. ignace.mpio@auralyon.com
authors.forename: Ignace
authors.initials: I
authors.lastname: Mpio
authors.forename: Nourredine
authors.initials: N
authors.lastname: Boumendjel
authors.forename: Husseyin
authors.initials: H
authors.lastname: Karaaslan
authors.forename: Walid
authors.initials: W
authors.lastname: Arkouche
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lenz
authors.forename: Carlos
authors.initials: C
authors.lastname: Cardozo
authors.forename: Jorge
authors.initials: J
authors.lastname: Cardozo
authors.forename: Myriam
authors.initials: M
authors.lastname: Pastural-Thaunat
authors.forename: Denis
authors.initials: D
authors.lastname: Fouque
authors.forename: Jacques
authors.initials: J
authors.lastname: Silou
authors.forename: David
authors.initials: D
authors.lastname: Attaf
authors.forename: Maurice
authors.initials: M
authors.lastname: Laville
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers; D002118:Calcium / Q000097:blood; D002130:Calcium Phosphates / Q000097:blood; D000069449:Cinacalcet; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D010758:Phosphorus / Q000097:blood; D010865:Pilot Projects; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002130:Calcium Phosphates; D006397:Hematinics; D006454:Hemoglobins; D009281:Naphthalenes; D010758:Phosphorus; C020243:calcium phosphate; D000469:Alkaline Phosphatase; D002118:Calcium; D000069449:Cinacalcet