Serum-soluble Fas and serum levels of erythropoietin in chronic kidney disease.
BACKGROUND
Soluble Fas levels (sFas) are increased in the serum of uremic patients and are associated with the presence of anemia and recombinant human EPO (rHuEPO) dosage in dialysis patients. It is possible that sFas levels are associated with an increased need for serum erythropoietin levels (Epo) in chronic kidney disease and dialysis patients in order to maintain hematocrit (Hct) levels.


OBJECTIVE
To investigate the relationship between serum sFas levels, serum Epo levels and the ratio between Epo levels and Hct in uremic patients.


METHODS
We studied 52 predialysis chronic kidney disease patients (CKD; 33 M, 57 +/- 12 years, hematocrit (Hct) = 37 +/- 7%), 29 peritoneal dialysis patients (PD; 12 M, 54 +/- 14 years, Hct = 36 +/- 7%), 29 hemodialysis patients (HD; 19 M, 47 +/- 14 years, Hct = 33 +/- 5%) and 29 healthy volunteers (control group 17 M, 50 +/- 16 years, Hct = 43 +/- 3%). We examined the relationship between Hct and serum levels of Epo, sFas, C-reactive protein, IL-6 and iron status. The ratio of serum Epo divided by Hct (Epo/Hct) was used as an indicator of Epo responsiveness.


RESULTS
Compared to normal subjects, the CKD, PD and HD groups presented lower Hct levels and higher serum levels of sFas, Epo, Epo/Hct and IL-6. Serum levels of sFas correlated negatively with albumin (r = -0.24, p = 0.02), IL-6 (r = -0.18, p = 0.04) and Epo/Hct (r = -0.37, p < 0.001). In multivariate analysis, after adjusting for markers of iron store and inflammation, only sFas correlated with Epo/Hct. In the CKD group, there were negative correlations between serum levels of sFas and glomerular filtration rate (GFR) (r = -0.45, p < 0.001) and between Epo/Hct and GFR (r = -0.32; p = 0.02). There was a positive correlation between Epo/Hct and serum levels of sFas in the CKD group (r = 0.31, p = 0.03) and in the HD groups (r = 0.58, p = 0.001).


CONCLUSIONS
Our findings show that serum sFas is associated with higher Epo/Hct ratio, suggesting that sFas may be a marker of Epo hyporesponsiveness in uremia. Further studies are needed to determine whether sFas is just a marker of Epo hyporesponsiveness or is also involved in its pathophysiology.
Góes
M A
MA
Federal University of São Paulo, UNIFESP, São Paulo, Brazil. miguelangelo@nefro.epm.br
Dalboni
M A
MA
Manfredi
S R
SR
Cendoroglo
M S
MS
Batista
M C
MC
Canziani
M E
ME
Balakrishnan
V S
VS
Pereira
B J G
BJ
Draibe
S A
SA
Cendoroglo
M
M
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000150:complications; D002097:C-Reactive Protein / Q000378:metabolism; D016009:Chi-Square Distribution; D004921:Erythropoietin / Q000097:blood*; D053222:Fas Ligand Protein / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012044:Regression Analysis; D006435:Renal Dialysis
D053222:Fas Ligand Protein; D015850:Interleukin-6; D004921:Erythropoietin; D002097:C-Reactive Protein; D007501:Iron