Pentoxifylline Improves Hemoglobin Levels in Patients with Erythropoietin-resistant Anemia in Renal Failure

Abstract

Abstract. It was hypothesized that pentoxifylline might improve the response to recombinant human erythropoietin (rhEpo) in anemic renal failure patients. Sixteen patients with ESRD and rh-Epo-resistant anemia, defined by a hemoglobin of Ͻ10.7 g/dl for 6 mo before treatment and a rh-Epo dose of Ն12,000 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-␣) and interferon gamma (IFN-␥) 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 Ϯ 0.9 g/dl. After 4 mo of pentoxifylline treatment, the mean hemoglobin concentration increased to 11.7 Ϯ 1.0 g/dl (P ϭ 0.0001). Baseline ex vivo T cell expression of TNF-␣ decreased from 58% Ϯ 11% to 31% Ϯ 23% (P ϭ 0.0007) after therapy. Likewise, IFN-␥ expression decreased from 31% Ϯ 10% to 13% Ϯ 10% (P ϭ 0

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

“…Thalidomide, a drug with immune-modulatory, anti-inflammatory, and antiangiogenic properties, exerts its therapeutic effects through the modulation of TNF; however, its teratogenic effect prevents its usage in the clinic. Pentoxifylline has been shown to reduce TNF expression by more than 50% and to improve hemoglobin levels in a small group of HD patients with erythropoietin-resistant anemia [32] . Several anti-inflammatory drugs (tocilizumab, canakinumab, pentoxifylline) have been recognized to be effective in other inflammatory diseases; however, there is still lack of data regarding the safety and concrete benefits of these medications in dialysis patients.…”

The Role of Inflammatory Cytokines in Diabetic Nephropathy

“…120,121 In addition, PTF shows a significant effect in modulating IFN-␥, IL-1␤, and IL-6. [122][123][124] In different models of renal disease where TNF-␣ plays a central role, such as lupus nephritis and crescentic glomerulonephritis, PTF prevents or attenuates renal injury. 125,126 Regarding diabetic nephropathy, recent experimental studies show that administration of PTF prevents an increase in renal expression, synthesis, and excretion of TNF-␣ during diabetes, which was directly and significantly associated with a reduction in renal sodium retention, renal hypertrophy, and urinary albumin excretion.…”

ESAs in Dialysis Patients

“…29 Optimizing adequacy of dialysis or switching patients to alternative modalities, such as peritoneal dialysis 30 or nocturnal 31 hemodialysis, may also result in lower ESA dosage. Treating inflammation either with drugs, such as pentoxyfilline 32 or a statin, 33 or treating an underlying infection or treating hyperparathyroidism also seem effective in reducing ESA dosage without causing the Hb to fall. For some patients who are waiting for a kidney allograft, long-term ESA therapy will be necessary because blood transfusion must be avoided to minimize the risk for sensitization.…”