Pentoxifylline improves hemoglobin levels in patients with erythropoietin-resistant anemia in renal failure.
It was hypothesized that pentoxifylline might improve the response to recombinant human erythropoietin (rh-Epo) in anemic renal failure patients. Sixteen patients with ESRD and rh-Epo-resistant anemia, defined by a hemoglobin of <10.7 g/dl for 6 mo before treatment and a rh-Epo dose of > or =12,000 IU/wk, were recruited. They were treated with oral pentoxifylline 400 mg o.d. for 4 mo. Ex vivo T cell generation of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) from the patients was assessed before treatment and 6 to 8 wk after therapy. A total of 12 of 16 patients completed the study. Before therapy, the 12 patients' mean hemoglobin concentration was 9.5 +/- 0.9 g/dl. After 4 mo of pentoxifylline treatment, the mean hemoglobin concentration increased to 11.7 +/- 1.0 g/dl (P = 0.0001). Baseline ex vivo T cell expression of TNF-alpha decreased from 58% +/- 11% to 31% +/- 23% (P = 0.0007) after therapy. Likewise, IFN-gamma expression decreased from 31% +/- 10% to 13% +/- 10% (P = 0.0002). Pentoxifylline therapy may significantly improve the hemoglobin response in patients with previously rh-Epo-resistant anemia in renal failure. This may occur due to inhibition of proinflammatory cytokine production, which could interfere with the effectiveness of rh-Epo.
Cooper
Angela
A
Department of Renal Medicine, GKT School of Medicine, King's College Hospital, London, United Kingdom.
Mikhail
Ashraf
A
Lethbridge
Mark W
MW
Kemeny
D Michael
DM
Macdougall
Iain C
IC
D000328:Adult; D000368:Aged; D000740:Anemia / Q000150:complications*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D051437:Renal Insufficiency / Q000150:complications*; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D016166:Free Radical Scavengers; D006454:Hemoglobins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D007371:Interferon-gamma; D010431:Pentoxifylline