Hyporesponsiveness to erythropoietin therapy in hemodialyzed patients: potential role of prohepcidin, hepcidin, and inflammation.
Hepcidin is the key regulator of iron metabolism. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietic-stimulating agents. The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy, with particular attention being paid to erythropoietin-hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Germany (ELISA method) and Bachem, UK (RIA method). TNFalpha and IL-6 were studied using kits from and R&D (Abington, UK), and hsCRP was studied using kits from American Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and residual renal function, and significantly higher serum ferritin, hsCRP, IL-6, TNFalpha, and erythropoietin dose. The difference in serum prohepcidin and hepcidin did not reach statistical significance; however, there was a tendency toward higher values of both prohepcidin and hepcidin in hyporesponsive patients. In conclusion, though hyporesponsiveness to erythropoietin therapy occur in dialyzed patients, it is mainly associated with subclinical inflammation than with hepcidin excess. Further studies are needed to develop a reliable and reproducible assay to elucidate the potential contribution of hepcidin to hyporesponsiveness during erythropoietin therapy.
Department of Nephrology and Transplantology, Medical University, Bialystok, Poland. jolmal@poczta.onet.pl
Jolanta
J
Malyszko
Jacek S
JS
Malyszko
Michal
M
Mysliwiec
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy / Q000209:etiology; D023181:Antimicrobial Cationic Peptides / Q000187:drug effects / Q000378:metabolism*; D001774:Blood Chemical Analysis; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005293:Ferritins / Q000097:blood / Q000627:therapeutic use; D005500:Follow-Up Studies; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011336:Probability; D011498:Protein Precursors / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D018836:Inflammation Mediators; D015850:Interleukin-6; D011498:Protein Precursors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D005293:Ferritins