Inflammation, T-cell phenotype, and inflammatory cytokines in chronic kidney disease patients under hemodialysis and its relationship to resistance to recombinant human erythropoietin therapy.
BACKGROUND
Resistance to recombinant human erythropoietin (rhEPO) occurs in some chronic kidney disease (CKD) patients, which may be due to enhanced systemic inflammatory response and to the erythropoiesis-suppressing effect of pro-inflammatory cytokines, some of which are produced by T cells.


OBJECTIVE
The aim of this study was to investigate the relationship between resistance to rhEPO therapy in hemodialysis CKD patients and inflammatory markers [C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (sIL2R), and serum albumin levels], blood cell counts, T-cell phenotype, cytokine production by T cells, and serum cytokine levels.


METHODS
We studied 50 hemodialysis CKD patients, 25 responders and 25 nonresponders to rhEPO, and compared them to each other and with 25 healthy controls. When compared to controls, CKD patients showed increased serum levels of CRP, IL-6, and sIL2R and a T-cell lymphopenia, due to decreased numbers of both CD4+ and CD8+ T cells. T cells from CKD patients had an immunophenotype compatible with chronic T-cell stimulation as shown by the increased percentage of CD28-, CD57+, HLA-DR+, CD28-HLA-DR+, and CD57+ HLA-DR+ T cells and produce higher levels of IL-2, INF-gamma, and TNF-alpha after short-term in vitro stimulation, although Th1 cytokines were not detectable in serum. Statistically significant differences were found between responders and nonresponders to rhEPO therapy for total lymphocyte and CD4+ T-lymphocyte counts, albumin (lower in nonresponders) and CRP (higher in nonresponders) levels.


CONCLUSIONS
CKD patients under hemodialysis present with raised inflammatory markers and decrease of total lymphocyte and CD4+ T-lymphocyte counts when compared with controls. Some of those markers are even further enhanced in nonresponders to rhEPO therapy patients, but resistance to this therapy cannot be justified by a Th1 polarized T-cell response.
Costa
Elísio
E
Serviço de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Rua Anibal Cunha, 164, 4099-030 Porto, Portugal. elisio.costa@ipb.pt
Lima
Margarida
M
Alves
João Moura
JM
Rocha
Susana
S
Rocha-Pereira
Petronila
P
Castro
Elisabeth
E
Miranda
Vasco
V
do
Sameiro Faria Maria
SF
Loureiro
Alfredo
A
Quintanilha
Alexandre
A
Belo
Luís
L
Santos-Silva
Alice
A
D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D004351:Drug Resistance / Q000276:immunology*; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D011994:Recombinant Proteins; D006435:Renal Dialysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D004921:Erythropoietin