title: Recombinant human erythropoietin resistance in hemodialysis. Effects of paired filtration dialysis.
abstract: A percentage of hemodialysis (HD) patients are resistant to recombinant human erythropoietin (rHuEPO), a phenomenon that occurs less frequently in patients dialyzed with biocompatible membranes (M) and in peritoneal dialysis. The authors evaluated the effects of paired filtration dialysis (PFD)--a dialysis technique based on the use of an emophan M in conjunction with a polysulphone M--on erythropoiesis in HD patients resistant to rHuEPO. Twelve HD patients with anemia resistant to long-term therapy with rHuEPO (200.24 U/kg body weight three times per week intravenously for 10.2 months) were studied. Patients had been treated for an average of 46.9 months with bicarbonate HD, using cuprophan M (Phase A) and, successively, for 12 months by PFD (Phase B). The following parameters were evaluated monthly: 1) hemoglobin and hematocrit values; 2) serum levels of erythropoietin (EPO); and 3) serum levels of interleukin (IL)-3, IL-6, IL-10, IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). At the end of Phase A and Phase B, patients underwent bone marrow biopsies to evaluate 1) bone marrow burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) proliferative capacity, and 2) bone marrow mononuclear cell EPO-receptor (EPO-R) number. During Phase B, there was a progressive rise in hematocrit and hemoglobin values, so that within the sixth month, the rHuEPO dose was reduced to 80 +/- 15 U/kg body weight three times per week. At the same time, an increase in serum IL-3, IL-6, and IL-10 levels was seen, whereas serum IL-1 beta, TNF-alpha, and IFN-gamma levels decreased. This was accompanied by a rise in BFU-E and CFU-E growth and in bone marrow mononuclear cell EPO-R number. During Phase B, after the dialysis session, serum EPO levels increased by about 30% in comparison with pre dialysis values, whereas during Phase A they decreased by about 14%. In HD patients, EPO resistance may caused either by absorption of rHuEPO to the cuprophan M, or an increased release of cytokines that inhibit erythropoiesis, such as IL-1 beta, TNF-alpha, and IFN-gamma, and to a decrease in stimulatory cytokines such as IL-3, IL-6, and IL-10. These negative phenomena are reversed by the use of biocompatible dialysis techniques such as PFD.
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, St. Paul's Hospital, Savona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Carozzi
authors.forename: M G
authors.initials: MG
authors.lastname: Nasini
authors.forename: O
authors.initials: O
authors.lastname: Santoni
authors.forename: A
authors.initials: A
authors.lastname: Tirotta
authors.forename: A
authors.initials: A
authors.lastname: Sanna
mesh_terms: D000328:Adult; D000740:Anemia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D001672:Biocompatible Materials; D016207:Cytokines / Q000097:blood; D004351:Drug Resistance; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007688:Kidneys, Artificial; D008297:Male; D008875:Middle Aged; D011108:Polymers; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods*; D013450:Sulfones; D014511:Uremia / Q000150:complications / Q000628:therapy
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D006454:Hemoglobins; D011108:Polymers; D011994:Recombinant Proteins; D013450:Sulfones; D004921:Erythropoietin; C017662:polysulfone P 1700