A Possible Reason For ESA Resistance by ProQuest


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									Renal Week_1209     11/30/09    12:10 PM   Page 1

      14 Renal & Urology News                DECEMBER 2009

       s   Renal Week 2009, San Diego

      A Possible Reason                                                                          Hepcidin May
                                                                                                 Help Manage
      For ESA Resistance                                                                         Anemia
                                                                                                 PLASMA HEPCIDIN may be a
                                                    ESA, we identified significantly high-       more useful guide to anemia manage-
        The articles on these pages and             er levels of inflammatory markers            ment in hemodialysis (HD) patients
        on page 16 report on studies                CRP and IL-6, which could be in the          than traditional iron parameters, ac-
        presented at the American                   causal pathway for adverse outcomes          cording to British investigators.
        Society of Nephrology’s Renal               associated with high-dose ESA,” she            They found that plasma hepcidin
        Week conference in San Diego.               said. “Whether elevated inflamma-            levels predict hemoglobin (Hb)
                                                    tory biomarkers are directly caused          response to IV iron loading and may
                                                    by higher ESA doses or are simply a          reflect adequate iron availability or rel-   Damien Ashby, MD
       BY JODY A. CHARNOW                           marker of a sicker patient popula-           ative erythropoietin deficiency. Hepci-
       RESEARCHERS HAVE recently                    tion—who require higher doses—               din—a hormone made in the liver—             erythropoietin dose, C-reactive pro-
       found evidence that could help               remains to be determined.”                   inhibits iron absorption and recycling.      tein, and albumin.
       explain why some anemic CKD                    Dr. Inrig noted that the study is the        Damien Ashby, MD, of the Imperial            In a separate study of six healthy
       patients are resistant to treatment          first to reveal in vivo a direct relation-   College Kidney and Transplant Insti-         individuals, the same research team
       with an erythropoiesis stimulating           ship between ESA dose and soluble            tute, Hammersmith Hospital, London,          found that erythropoietin administra-
       agents (ESA).                                Epo receptor as a potential modu-            and colleagues measured plasma hep-          tion is associated with a profound
         Jula K. Inrig, MD, MPH, Assistant          lator of erythropoietic response to          cidin levels in 67 stable HD patients        reduction in circulating hepcidin. In
       Professor of Medicine at the                 ESA therapy. Although a recombi-             before IV iron loading, which was indi-      the study, Dr. Ashby’s group measured
       University of Texas Southwestern             nant form of sEpoR was shown to act          cated by subthreshold levels of ferritin     plasma iron parameters at multiple
       Medical Center in Dallas, and collab-                                                     (below 400 ng/mL) or iron (less than         timepoints before and after a single
       orators studied 32 CKD patients                                                           10 nmol/mL). Patients then received          injection of erythropoietin and meas-
       receiving anemia treatment with dar-         A lower pill                                 200 mg iron sucrose IV at each of the        ured hepcidin with a recently devel-
       bepoetin-α: 21 who were receiving            burden for patients                          next five HD sessions, with Hb re-           oped radioimmunoassay.
       usual doses (mean 49.7 mcg/week)                                                          sponse assessed the following month.           In all subjects, erythropoietin in-
       and 11 who were receiving high               may be possible,                               Of the 67 subjects, 43 (64%) were          jection was followed by a marked
       doses (94.1 mcg/week). The patients
       in the two groups had similar base-
                                                    researcher says.                             responders, defined as patients whose
                                                                                                 Hb increased after iron loading.
                                                                                                                                              reduction in circulating hepcidin last-
                                                                                                                                              ing more than 14 days; erythropoie-
       line characteristics, although the                                                        Plasma hepcidin levels at baseline were      tin levels returned to baseline by
       high-dose group had lower three-             as an antagonist of Epo in in vitro and      significantly higher in subsequent non-      seven days. In addition, levels of circu-
       month average hemoglobin levels.             in vivo studies of Epo-EpoR biology          responders than in responders, the    
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