Inflammation and erythropoietin hyporesponsiveness - Role of pentoxifylline - An anti TNF-α agent

Introduction: Resistance to erythropoiesis-stimulating agents (ESAs) is often associated with chronic inflammation present in patients of chronic kidney disease (CKD) on maintenance hemodialysis (MHD). This study was planned to investigate how anemia, ESA resistance and the plasma levels of biological markers of inflammation are interlinked to each other and whether Pentoxifylline (PTF) has any role in improving anemia in these subset of patients. Methods: 20 adult patients of end stage renal disease (ESRD) with erythropoietin hyporesponsiveness undergoing twice weekly maintenance hemodialysis were administered subcutaneously 6,000 IU of recombinant human erythropoietin (rHuEPo) twice weekly following dialysis for two months followed by addition of Pentoxifylline to erythropoietin for next four months to complete the study period of six months. The effect of erythropoietin and pentoxifylline on hemoglobin, hematocrit and inflammatory markers that included high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), erythrocyte sedimentation rate (ESR), serum albumin and serum ferritin were studied. Results: There was a insignificant response of erythropoietin alone on hemoglobin and hematocrit after 2 months of rHuePo therapy ('p'>0.05), associated with insignificant decrease in hsCRP, TNF-á and ESR, respectively over 2 months but when Pentoxifylline was added to erythropoietin, the rise in hemoglobin and hematocrit was highly significant ('p'<0.01) which was associated with highly significant decrease in hsCRP, TNF-αand ESR, respectively after completion of the study ('p'<0.01). Conclusion: Pentoxifylline has significant effect in reducing the inflammatory parameters in CKD patients on MHD and therefore is a promising agent in improving anemia in patients of ESRD showing erythropoietin hyporesponsiveness, attributable to inflammation.