Erythrocyte PAF-acetylhydrolase activity in various stages of chronic kidney disease: effect of long-term therapy with erythropoietin.
BACKGROUND
Erythrocytes represent an important component of the antioxidant capacity of blood, comprising, in particular, intracellular enzymes, including platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (Gpx). We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease (CKD), and further investigated whether erythropoietin (EPO) administration in these patients has any influence on the enzyme activities.


METHODS
Thirty-six patients (19 men and 17 women) with CKD (stages 1 to 5) participated in the study. Thirteen of them presented with CKD stage 1 to 2 (group I), whereas 23 patients presented with CKD stage 3 to 5 and randomized into two groups (i.e., groups II and III). Patients of group II (N= 11) were administered EPO subcutaneously, 50 units per kg once per week. In group III (N= 12), EPO was initiated only when the hemoglobin (Hb) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months. Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls. The PAF-AH and Gpx activities were determined in isolated washed erythrocytes.


RESULTS
The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls, the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied populations, both enzyme activities were negatively correlated with the creatinine clearance values. Importantly, the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO (group III), a phenomenon not observed in patients receiving EPO (group II), or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III.


CONCLUSIONS
Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients. Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency, thus preserving the erythrocyte defense mechanisms against oxidative stress.
Papavasiliou
Eleni C
EC
Laboratory of Biochemistry, Department of Chemistry, Medical School, University of Ioannina, Ioannina, Greece.
Gouva
Chariklia
C
Siamopoulos
Kostas C
KC
Tselepis
Alexandros D
AD
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D005979:Glutathione Peroxidase / Q000378:metabolism; D006454:Hemoglobins; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D006454:Hemoglobins; D017392:Thiobarbituric Acid Reactive Substances; D004921:Erythropoietin; D005979:Glutathione Peroxidase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase