Oxidative stress, inflammation and nutritional status during darbepoetin alpha treatment in peritoneal dialysis patients.
Recombinant human erythropoetin beta; (rHuEPO) has not only an erythropoietic effect but also appears to affect production of cytokines and may improve nutritional status of dialysis patients. Darbepoetin alpha; is a new erythropoiesis-stimulating protein with a threefold longer serum half-life when compared with rHuEPO. The objective of this prospective study was to assess oxidative stress, inflammation, nutrition and hematological response in peritoneal dialysis (PD) patients who were switched from rHuEPO beta to darbepoetin alpha. 12 stable PD patients (6 M, 6 F; mean age 56.2 +/- 15.1 yr.) were evaluated during this study together with 22 healthy volunteers serving as a control group. All patients had been receiving erythropoetin beta subcutaneously once a week before they were reassigned to darbepoetin. The new drug was administered every other week for 6 months, in a dose equivalent to a weekly dose of previously taken rHuEPO. Hematology, iron status and biochemical profiles were evaluated monthly. Markers of oxidative stress: malondialdehyde/ 4-hydroxynoneal (MDA/4HNE), carbonyl groups (CG), oxyLDL and AGEs and markers of inflammation: CRP, TNF alpha, IL-6 were measured on rHuEPO beta before the switch to darbepoetin, and after 1st and 6th month of darbepoetin treatment. The assessment of nutritional status was determined by body mass index (BMI), serum albumin concentration and Subjective Global Assessment (SGA).


RESULTS
Mean levels of Hb and Hct were stable during 6 months of observation and not significantly different from the data observed for on rHuEPO. Nutritional status was good in 9 patients, 3 patients were malnourished at the beginning of this study as assessed by SGA and this status persisted to the end of observation. The levels of markers of oxidative stress and inflammation were statistically higher than in the control group (p < 0.05).


CONCLUSIONS
Darbepoetin alpha given subcutaneously once every 2 weeks is effective for the treatment of anemia in PD patients. Less frequent administration of darbepoetin has a biological response similar to weekly administration of rHuEPO.
Malgorzewicz
S
S
Department of Nephrology, Transplantation and Internal Medicine, Medical University Gdansk, Gdansk, Poland. sylwia@tetra.pl
Lichodziejewska-Niemierko
M
M
Lizakowski
S
S
Liberek
T
T
Lysiak-Szydlowska
W
W
Rutkowski
B
B
D000328:Adult; D000447:Aldehydes / Q000097:blood; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009752:Nutritional Status / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010530:Peritoneal Dialysis; D011446:Prospective Studies; D011994:Recombinant Proteins; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D000447:Aldehydes; D015415:Biomarkers; D006397:Hematinics; D011994:Recombinant Proteins; D012709:Serum Albumin; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D008315:Malondialdehyde; D002097:C-Reactive Protein; C027576:4-hydroxy-2-nonenal