Neutrophil and monocyte activation in chronic kidney disease patients under hemodialysis and its relationship with resistance to recombinant human erythropoietin and to the hemodialysis procedure

Pereira, Rui; Costa, Elı́sio; Gonçalves, Marta; Miranda, Vasco; Faria, Maria do Sameiro; Quintanilha, Alexandre; Belo, Luı́s; Lima, Margarida; Santos-Silva, Alice

doi:10.1111/j.1542-4758.2010.00450.x

Cited by 29 publications

(17 citation statements)

References 26 publications

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“…It has been shown that activated antigen-specific T cells, B cells, and monocytes produced BDNF 18. Uremic inflammatory state is characterized by enhanced immune system which involves both T lymphocytes and monocytes 19. Therefore, it is postulated that chronic inflammatory condition and enhanced immune system is associated with the production of BDNF, which may explain the reason that the plasma BDNF level in non-diabetic HD patients was higher compared to that of control subjects in this study.…”

Section: Discussionmentioning

confidence: 52%

Plasma Brain-derived Neurotrophic Factor in Hemodialysis Patients

Shin¹,

Yoon²,

Chung³

et al. 2012

Int. J. Med. Sci.

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Objective: Brain-derived neurotrophic factor (BDNF) is a neurotrophin which modulates neuronal survival and proliferation. Recently, plasma BDNF is associated with inflammatory conditions. The present study was to investigate the changes of the plasma BDNF level in hemodialysis patients and to evaluate the relationship between the plasma BDNF and uremic inflammation.Method: We measured the plasma BDNF, serum IL-2, IL-4, IFN-γ and TNF-α in hemodialysis patients and control subjects. In addition, we investigated the associations of the plasma BDNF with clinical or biochemical parameters.Results: The plasma BDNF level was significantly higher in hemodialysis patients than in the control subjects (median, 312.3 vs. 630.3 pg/ml, p < 0.05). In subgroup analysis, hemodialysis patients with diabetes showed higher values of the plasma BDNF than the patients without diabetes. However, there were no significant differences in age and gender subgroups of the hemodialysis patients. The logBDNF was positively correlated with hs-CRP and IFN-γ, and negatively correlated with serum albumin. In multivariate regression analysis, the logBDNF was independently associated with the presence of diabetes (β-coefficient = 0.399, p = 0.041) and IFN-γ (β-coefficient = 0.538, p = 0.003).Conclusion: The plasma BDNF may increase in hemodialysis patients, and more prominently in the patients with diabetes. Furthermore, the plasma BDNF might reflect inflammatory condition in hemodialysis patients.

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Section: Discussionmentioning

confidence: 52%

Plasma Brain-derived Neurotrophic Factor in Hemodialysis Patients

Shin¹,

Yoon²,

Chung³

et al. 2012

Int. J. Med. Sci.

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“…Interestingly, although HD activates inflammatory responses, which promote MMPs release [19], no study has shown increased MMP-2 levels after an HD session. Neutrophil and monocyte activation in CKD patients under HD have been reported [37]. It is expected that increasing neutrophil MMP-9 could be detected in the circulation of HD patients under HD.…”

Section: Discussionmentioning

confidence: 97%

Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis

Yang

Hsieh

et al. 2015

Clin Exp Nephrol

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Background Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) play important roles in the pathophysiology of renal diseases. Imbalanced MMPs/TIMPs are implicated in the vascular alterations of uremic patients on hemodialysis (HD). We have investigated the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in uremic patients and the effects of a course of HD on the changes in these factors. Methods There were 382 uremic patients on regular HD treatment and 50 healthy controls enrolled in this study. The plasma MMP-2 and MMP-9 levels were detected by gelatin zymography, and TIMP-1 and TIMP-2 concentrations were determined by ELISA assay. Results Significantly higher plasma MMP-2 and MMP-9 and decreased TIMP-1 in the uremic patients were detected compared with those in the controls. Therefore, there were markedly higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in the uremic patients. In the course of a single HD session, the plasma MMP-2 level was significantly decreased from pre-HD to post-HD. TIMP-1 concentration was significantly increased from pre-HD to post-HD. Although the HD session did not have a significant effect on the levels of plasma MMP-9 and TIMP-2, both plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios were significantly decreased from pre-HD to post-HD levels.Conclusion HD session could decrease MMP-2 and increase TIMP-1 level in the circulation of uremic patients. The physiological significance of reduced MMPs/TIMPs ratio due to a single HD session is required to further validate.Keywords Hemodialysis Á Matrix metalloproteinase Á Tissue inhibitor of matrix metalloproteinase Á Uremic patient

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“…Interestingly, darbepoetin alpha treatment was associated with an increase in MIF, which helps to sustain macrophage activation and is an important mediator of anemic complications and bone marrow suppression during malaria infection [31,32], and could therefore also contribute to resistance to EPO. Furthermore, in patients with chronic kidney disease, nonresponders to EPO treatment are characterized by enhanced activation of both monocytes [33] and T cells [34]. Thus, although the RED-HF trial failed to detect a benefit of an erythropoiesis stimulating agent on clinical outcomes, leukocyte activation markers could be potentially identify patients that could have advantage of EPO treatment.…”

Section: Discussionmentioning

confidence: 99%