Inflammatory markers and platelet aggregation tests as predictors of hemoglobin and endogenous erythropoietin levels in hemodialysis patients.
OBJECTIVE
Chronic inflammation is a common cause of severe anemia and hyporesponsiveness to recombinant erythropoietin (EPO) therapy in maintenance hemodialysis (HD) patients. We compared various acute-phase markers and ex vivo platelet aggregation tests in relation to clinical conditions in order to find factors predictive of hemoglobin (Hb) and endogenous EPO levels in a cross-section of clinically stable HD patients.


METHODS
In 100 subjects, pre-HD blood levels of C-reactive protein (CRP), alpha(1)-acid-glycoprotein (AGP), alpha(1)-antitrypsin (AT), immunoglobulin (Ig) M and G (by nephelometry), antigens of endothelial von Willebrand factor (vWF), type 1 plasminogen activator inhibitor and thrombomodulin, interleukin-6, lipoprotein(a) [Lp(a)] and EPO (by ELISA), and albumin, fibrinogen, iron metabolism indices, thyroid-stimulating hormone, phosphorus, parathormone, total cholesterol, triglycerides, viral hepatitis B/C markers, liver enzyme, and aluminium were determined. Platelet aggregations in response to ristocetin (RIPA), adenosine diphosphate, and collagen were measured in whole blood (electric impedance method) and platelet-rich plasma (optical aggregometry).


RESULTS
Hb levels inversely correlated with IgM, Lp(a), soluble vWF antigen, phosphorus, and all platelet aggregations in whole blood, but not in platelet-rich plasma. HD duration and triglycerides were positive correlates of anemia. In a multivariable analysis, increased IgM, short HD duration, increased Lp(a) and enhanced whole blood RIPA (in descending order of significance) were independent predictors of low Hb levels. In 51 patients not treated with recombinant EPO, serum levels of this hormone inversely correlated with whole blood RIPA, AT, age, vWF antigen, AGP, and positively with viral hepatitis marker. Anemia and EPO levels were not affected by gender, body mass index, cause of renal failure, residual renal function, HD dose, protein catabolic rate, use of different heparins or dialysate buffers, ACE inhibitor therapy, and parathyroid or thyroid function. In additional 10 patients, single HD session resulted in an increase in IgM levels associated with a fall in total lymphocyte counts.


CONCLUSIONS
Subclinical inflammation is an important determinant of anemia in maintenance HD patients. Increased serum IgM reflecting a microinflammatory effect of HD procedures, enhanced whole blood RIPA as a surrogate of vascular endothelial damage, and Lp(a) as its promoter could be markers of such impaired erythropoiesis.
Department of Nephrology and Internal Medicine, Medical Academy, Białystok, Poland. jborawski@post.pl
Jacek
J
Borawski
Krystyna
K
Pawlak
Michał
M
Myśliwiec
D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000209:etiology; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D006435:Renal Dialysis
D015415:Biomarkers; D006454:Hemoglobins; D004921:Erythropoietin