Dysfunction of natural killer cells in end-stage kidney disease on hemodialysis

Nagai, Kei

doi:10.1186/s41100-021-00324-0

Cited by 8 publications

(11 citation statements)

References 50 publications

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“…The uremic milieu mediates increased apoptosis and resistance to interleukin 17 and B cell activation factor (BAFF) of B cells [29]. Concerning the numbers of NK cells and T cells in patients receiving dialysis treatment, the results of previous reports are controversial [30,31]. Some previous studies shared our observation of elevated proportions of NK cells [30,32,33], while others reported decreased percentages or no changes [20,34,35].…”

Section: Discussionmentioning

confidence: 55%

Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients

Friebus‐Kardash

Kuang

Peitz

et al. 2023

Cells

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Patients on dialysis have dysfunctions of innate and adaptive immune system responses. The transcriptional factor IRF8 (interferon regulatory factor 8) is primarily expressed in plasmacytoid cells (pDCs) and myeloid dendritic cells (mDCs), playing a crucial role in the maturation of dendritic cells, monocytes, and macrophages, and contributing to protection against bacterial infections. The current study analyzed the expression patterns of IRF8 and assessed its association with the risk of infections in 79 dialysis patients compared to 44 healthy controls. Different subsets of leukocytes and the intracellular expression of IRF8 were measured using flow cytometry. Compared to the healthy controls, the dialysis patients showed significantly reduced numbers of pDCs and significantly increased numbers of natural killer cells and classical and intermediate monocytes. The dialysis patients exhibited decreased numbers of IRF8-positive dendritic cells (pDC p < 0.001, mDC1 p < 0.001, mDC2 p = 0.005) and increased numbers of IRF8-positive monocytes (p < 0.001). IRF8 expression in pDC, mDC, and classical monocytes was lower in the dialysis patients than in the controls. Dialysis patients who required hospitalization due to infections within one year of follow-up displayed significantly reduced IRF8 expression levels in pDCs compared to patients without such infections (p = 0.04). Our results suggest that reduced IRF8 expression in pDCs is a potential risk factor predisposing dialysis patients to serious infections.

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Section: Discussionmentioning

confidence: 55%

Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients

Friebus‐Kardash

Kuang

Peitz

et al. 2023

Cells

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“…One explanation is that, in mRNA vaccines, the mRNA both encodes the viral antigen and acts as an adjuvant due to its innate immunostimulatory properties; the mRNA is recognized by endosomal and cytosolic innate sensors upon cell entry, resulting in cellular activation and production of type I interferons and other inflammatory mediators 36 . This elevated innate immune stimulus could overcome immune desensitization in ESRD, evidenced by diminished TLR4 expression on monocytes 37 and downregulation of activating receptors on natural killer cells in this population 38 . If so, the mRNA vaccine delivery vehicle could prove particularly valuable in vaccine development for ESRD and HD going forward.…”

Section: Discussionmentioning

confidence: 99%

Immune response to the mRNA COVID-19 vaccine in hemodialysis patients: cohort study

Chang

Kai

Lee

et al. 2023

Preprint

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Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines. Methods: A transcriptomic analysis of the immune response to the Covid-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells (PBMCs) was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and seven days after the second dose (V2D7) using anti-Spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified six months after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response. Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with predominant T cell activity in controls one week after the first vaccination dose, compared to predominant myeloid cell activity in HD at this time point. HD demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p < 0.05). Anti-spike IgG remained elevated above baseline at six months in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development. Conclusion: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance hemodialysis subjects (HD) comparable to healthy controls (HC) and identify transcriptomic and clinical predictors of anti-Spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of end stage renal disease (ESRD). Funding:F30HD102093, F30HL151182, T32HL144909, R01HL138628 This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003

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“…Moreover, evidence suggests that patients with advanced CKD may have a compromised immune response, thus being more vulnerable to postoperative infections, abscesses and sepsis. For instance, earlier studies report macrophage and natural killer cell dysfunction in end-stage kidney disease 32,33 and patients with CKD may therefore be at increased risk of infectious diseases. 34 There are some studies that have explored preoperative kidney function in pancreatic resections.…”

Section: Discussionmentioning

confidence: 99%

Preoperative chronic kidney disease and complications after pancreatoduodenectomy: a retrospective cohort study

Swartling,

Evans,

Larsson

et al. 2023

ANZ Journal of Surgery

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BackgroundChronic kidney disease is a prevalent condition in surgical patients. Possible associations with increased postoperative morbidity and mortality have not been clearly demonstrated in patients undergoing pancreatoduodenectomy. The aim of this study was to assess the risk of postoperative complications in patients with reduced kidney function undergoing pancreatoduodenectomy.MethodsAll patients undergoing pancreatoduodenectomy at Karolinska University Hospital between 2008 and 2019 were retrospectively included. The variable of interest was chronic kidney disease, based on preoperative estimated glomerular filtration rate measurements. Unadjusted and adjusted logistic regression analyses were performed for standardized postoperative complications.ResultsA total of 971 patients were included in the study, of whom 92 (10%) had an estimated glomerular filtration rate < 60 mL/min/1.73m2, equivalent to chronic kidney disease Stage 3a or worse. Patients with chronic kidney disease had a higher odds of longer hospital stay (adjusted odds ratio 1.58, 95% confidence interval 1.00–2.50) and postoperative weight increase (adjusted odds ratio 2.02, 1.14–3.56). A 10 unit increase of preoperative estimated glomerular filtration rate was associated to lower odds of intensive care unit admission (adjusted odds ratio 0.81, 0.69–0.95), delayed gastric emptying (adjusted odds ratio 0.90, 0.81–0.99), and post‐operative pancreatic fistula (adjusted odds ratio 0.83, 0.74–0.94).ConclusionPatients undergoing pancreatoduodenectomy with decreased preoperative kidney function are more likely to experience major postoperative complications, and also postoperative weight increase. Preoperative kidney function assessment is important in risk stratification before pancreatoduodenectomies.

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Dysfunction of natural killer cells in end-stage kidney disease on hemodialysis

Cited by 8 publications

References 50 publications

Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients

Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients

Immune response to the mRNA COVID-19 vaccine in hemodialysis patients: cohort study

Preoperative chronic kidney disease and complications after pancreatoduodenectomy: a retrospective cohort study

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