Characteris Tics and Causes of Immune Dysfunction Related to Uremia and Dialysis

Hauser, Aline Borsato; Stinghen, Andréa Emília Marques; Kato, Shinichi; Bucharles, Sérgio Gardano Elias; Aita, Carlos Alberto Mayora; Yuzawa, Yukio; Pécoits-Filho, Roberto

doi:10.1177/089686080802803s34

Cited by 145 publications

(49 citation statements)

References 34 publications

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“…That is, the functions of polymorphonuclear leukocytes, monocytes, macrophages, APCs, and lymphocytes in maintaining an efficient immune response are affected by multiple causes including increased oxidative stress and inflammation, priming of leukocytes, accumulation of uremic toxins, increased apoptosis of immune cells, disturbed renal metabolic effects, and dialysis-related factors (e.g., interactions between the blood and dialysis equipment, the presence of endotoxins in the water used for dialysis, access-related infections, and PD solutions with a high glucose concentration, low pH, or the presence of glucose degradation products represent chronic stimuli for the inflammatory response ( 2 3 4 5 6 7 8 9 10 ). These abnormalities of immune cells lead to an increased propensity to infection, a diminished response to vaccination, a decreased production of antibodies in response to specific stimuli by B cells, and an impaired cell-mediated immunity ( 8 9 10 ). Furthermore, it has been reported that dysfunctions of the immune system are associated with a high prevalence of cardiovascular disease and mortality in patients with ESRD ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

Dendritic Cell Dysfunction in Patients with End-stage Renal Disease

Kim

et al. 2017

Immune Netw

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End-stage renal disease (ESRD) with immune disorder involves complex interactions between the innate and adaptive immune responses. ESRD is associated with various alterations in immune function such as a reduction in polymorphonuclear leukocyte bactericidal activity, a suppression of lymphocyte proliferative response to stimuli, and a malfunction of cell-mediated immunity at the molecular level. ESRD also increases patients' propensity for infections and malignancies as well as causing a diminished response to vaccination. Several factors influence the immunodeficiency in patients with ESRD, including uremic toxins, malnutrition, chronic inflammation, and the therapeutic dialysis modality. The alteration of T-cell function in ESRD has been considered to be a major factor underlying the impaired adaptive cellular immunity in these patients. However, cumulative evidence has suggested that the immune defect in ESRD can be caused by an Ag-presenting dendritic cell (DC) dysfunction in addition to a T-cell defect. It has been reported that ESRD has a deleterious effect on DCs both in terms of their number and function, although the precise mechanism by which DC function becomes altered in these patients is unclear. In this review, we discuss the effects of ESRD on the number and function of DCs and propose a possible molecular mechanism for DC dysfunction. We also address therapeutic approaches to improve immune function by optimally activating DCs in patients with ESRD.

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Section: Introductionmentioning

confidence: 99%

Dendritic Cell Dysfunction in Patients with End-stage Renal Disease

Kim

et al. 2017

Immune Netw

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“…Recently, aberrant PTH/Ca/P levels have been linked to infection in dialysis patients beyond the scope of CKD-MBD and vascular calcification related cardiovascular morbidity and mortality 19 , 25 . The underlying mechanism may be associated with systemic immune dysregulation 26 , 27 . In fact, in vitro experimental data have indicated that immune cell functions could be modulated by different concentrations of PTH, Ca or P, although these functional alterations in uremic patients may not be consistent with in vitro data due to their complex interactions.…”

Section: Discussionmentioning

confidence: 99%

Aberrant serum parathyroid hormone, calcium, and phosphorus as risk factors for peritonitis in peritoneal dialysis patients

Liao

Zheng

Lin

et al. 2021

Sci Rep

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Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.

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“…Uremia-related immune dysfunction is a complex interaction between the innate and adaptive systems, in which persistent immune activation and immune suppression coexist [ 15 ]. The pathogenic mechanisms of these immunological abnormalities have been ascribed in part to uremic toxins, malnutrition, iron overload, dialysis-related factors, and possibly apoptosis [ 16 – 19 ].…”

Section: Discussionmentioning

confidence: 99%

Neutrophil apoptosis: impact of granulocyte macrophage colony stimulating factor on cell survival and viability in chronic kidney disease and hemodialysis patients

Zahran¹,

Sayed²,

William³

et al. 2013

aoms

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IntroductionAltered neutrophil apoptosis might be responsible for recurrent bacterial infections encountered in hemodialysis (HD) and chronic kidney disease (CKD) patients. This work was designed to assess the neutrophil apoptotic activity and the impact of implementation of granulocyte macrophage colony stimulating factor (GM-CSF), as a survival factor, on neutrophil apoptosis among these patients.Material and methodsTwenty-five patients on regular HD along with 34 CKD patients on conservative treatment, as well as 15 healthy controls, were investigated for apoptotic rate via assessment of neutrophil expression of Annexin-V by flow cytometry, before and after 20 h culture in absence and presence of GM-CSF. Neutrophil viability was determined using light microscopy. The preservation of neutrophil activation in these patients was analyzed by flow cytometric CD18 neutrophil expression. Chronic inflammatory state was evaluated by estimating C-reactive protein (CRP) and soluble intercellular adhesion molecule-1 (sICAM-1). Obtained data were statistically analyzed.ResultsCompared to controls, both HD and CKD groups had a significant increase of Annexin-V and CD18 expression and significant decrease in neutrophil viability. Culture of their neutrophils with GM-CSF showed significant decrease of apoptosis accompanied by improvement of neutrophil viability compared to their cultured cells without GM-CSF. These patients also showed significant elevation of CRP and sICAM-1.ConclusionsGranulocyte macrophage colony stimulating factor demonstrated an evident impact on improving in vitro neutrophil survival and viability in HD and CKD patients. Therefore, this may represent promising preventive and/or therapeutic strategies against infection frequently observed in these patients and causing morbidity and mortality.

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Characteris Tics and Causes of Immune Dysfunction Related to Uremia and Dialysis

Cited by 145 publications

References 34 publications

Dendritic Cell Dysfunction in Patients with End-stage Renal Disease

Dendritic Cell Dysfunction in Patients with End-stage Renal Disease

Aberrant serum parathyroid hormone, calcium, and phosphorus as risk factors for peritonitis in peritoneal dialysis patients

Neutrophil apoptosis: impact of granulocyte macrophage colony stimulating factor on cell survival and viability in chronic kidney disease and hemodialysis patients

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