title: CMV seropositivity determines epoetin dose and hemoglobin levels in patients with CKD.
abstract: Cytomegalovirus (CMV)-seropositive patients with ESRD may have more CD4(+) T cells lacking the co-stimulatory molecule CD28 (CD4(+)CD28null) than CMV-seronegative patients. Increased numbers of CD28null T cells associates with epoetin nonresponsiveness in patients with ESRD, but whether expansion of CD4+CD28null T cells in CMV-seropositive patients associates with demand for epoetin is unknown. In a cohort of 129 stable patients with ESRD, CMV seropositivity significantly associated with a lower hemoglobin level in predialysis patients (12.5 versus 11.5 g/dl; P < 0.02). CMV seropositivity did not associate with average hemoglobin level in hemodialysis patients, but CMV-seropositive patients required significantly more epoetin (median 12,000 versus 6300 U/wk; P = 0.02). Multivariate linear regression analysis identified CMV seropositivity as the only variable significantly associated with hemoglobin levels in predialysis patients and epoetin dosages in hemodialysis patients. In CMV-seropositive hemodialysis patients, the number of circulating CD4(+)CD28null T cells positively correlated with epoetin dosage. These CD4(+)CD28null T cells were proinflammatory; they were capable of producing large amounts of IFN-gamma and TNF-alpha. In conclusion, expansion of CD4(+)CD28null T cells in CMV-seropositive patients with ESRD associates with increased demand for epoetin.
authors.affiliation: Erasmus Medical Center, Department of Internal Medicine, Division of Nephrology, Dr. Molewaterplein 40, Rotterdam, Netherlands. m.g.h.betjes@erasmusmc.nl
authors.forename: Michiel G H
authors.initials: MG
authors.lastname: Betjes
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Nicolle H R
authors.initials: NH
authors.lastname: Litjens
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000276:immunology; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000914:Antibodies, Viral; D018106:CD28 Antigens; D006454:Hemoglobins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C103998:epoetin beta; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D007371:Interferon-gamma