Inflammation, T-cell phenotype, and inflammatory cytokines in chronic kidney disease patients under hemodialysis and its relationship to resistance to recombinant human erythropoietin therapy

Elísio Costa, Margarida Lima, João Moura Alves, Susana Rocha, Petronila Rocha-Pereira, Elisabeth Castro, Vasco Miranda, Sameiro Faria Maria do, Alfredo Loureiro, Alexandre Quintanilha, Luís Belo, Alice Santos-Silva, Elísio Costa, Margarida Lima, João Moura Alves, Susana Rocha, Petronila Rocha-Pereira, Elisabeth Castro, Vasco Miranda, Sameiro Faria Maria do, Alfredo Loureiro, Alexandre Quintanilha, Luís Belo, Alice Santos-Silva

Abstract

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.

Aim of study: 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.

Materials and 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.

Conclusion: 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.

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