The Association of Circulating CD14++CD16+ Monocytes, Natural Killer Cells and Regulatory T Cells Subpopulations With Phenotypes of Cardiovascular Disease in a Cohort of Peritoneal Dialysis Patients

Abstract

The altered expression of immune cells including monocyte subsets, natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in end-stage kidney disease, affect the modulation of inflammation and immunity with significant clinical implications. The aim of this study was to investigate the profile of specific immune cells subpopulations and their correlations with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in peritoneal dialysis (PD) patients.Materials and Methods: 29 stable PD patients and 13 healthy volunteers were enrolled. Demographic, laboratory, bioimpedance measurements, lung ultrasound and echocardiography data were collected. The peripheral blood immune cell subsets analysis was performed using flow cytometry.Results: PD patients compared to normal controls had lower total lymphocytes (22.3 ± 6.28 vs. 31.3 ± 5.54%, p = <0.001) and B-lymphocytes (6.39 ± 3.75 vs. 9.72 ± 3.63%, p = 0.01) as well as higher CD14++CD16+ monocytes numbers (9.28 ± 6.36 vs. 4.75 ± 2.75%, p = 0.0002). PD patients with prevalent CAD had NK cells levels elevated above median values (85.7 vs. 40.9%, p = 0.04) and lower B cells counts (3.85 ± 2.46 vs. 7.2 ± 3.77%, p = 0.03). Patients with increased NK cells (>15.4%) had 3.8 times higher risk of CAD comparing with patients with lower NK cell levels (95% CI, 1.86 – 77.87; p = 0.034). B cells were inversely associated with the presence of CAD (increase of B-lymphocyte by 1% was associated with 30% less risk for presence of CAD (95% CI, −0.71 – 0.01; p = 0.05). Overhydrated patients had lower lymphocytes counts (18.3 ± 4.29% vs. 24.7 ± 6.18%, p = 0.006) and increased NK cells [20.5% (14.3, 23.6) vs. 13.21% (6.23, 19.2), p = 0.04)]. In multiple logistic regression analysis the CRP (OR 1.43; 95% CI, 1.00 – 2.05; p = 0.04)] and lymphocytes counts (OR 0.79; 95% CI, 0.63–0.99; p = 0.04)] were associated with the presence of lung comets. Patients with higher NK cells (>15.4%, n = 15) were more likely to be rapid transporters (D/P creatinine 0.76 ± 0.1 vs. 0.69 ± 0.08, p = 0.04). Patients displaying higher Tregs (>1.79%) were older (70.8 ± 10.7 years vs. 57.7 ± 14.7years, p = 0.011) and had higher nPCR (0.83 ± 0.14 vs. 0.91 ± 0.17, p = 0.09).Conclusion: Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients at the highest risk for complications and guide interventions.

Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance

“…As indicated by unsupervised clustering and confirmed by hierarchic gating, we demonstrated a pathologic shift from classic toward intermediate and nonclassic monocytes in patients on HD. This monocyte signature was previously associated with an increased risk of CVD 44 , 45 . Most notably, we showed that isolated monocytes exhibited a higher production of TNF- α after incubation with serum from patients on HD compared with HCs, which was dependent on AhR function.…”

“…This monocyte signature was previously associated with an increased risk of CVD. 44,45 Most notably, we showed that isolated monocytes exhibited a higher production of TNF-a after incubation with serum from patients on HD compared with HCs, which was dependent on AhR function. Thus, the increased TNF-a concentrations in circulation are, at least partly, a consequence of the effect of the increased and mainly microbially produced TRP metabolites on the AhR of monocytes.…”

Differences in the Profile of Circulating Immune Cell Subsets in Males with Type 2 Cardiorenal Syndrome versus CKD Patients without Established Cardiovascular Disease

“…There are few and relatively recently published studies that have found elevated CD14++CD16+ monocyte counts in patients with both acute and stable chronic heart failure as well as an association of these proinflammatory monocytes with heart failure severity and decreased GFR levels [ 28 , 29 , 30 ]. Likewise, in CKD patients, the intermediate monocyte counts are higher than those in healthy subjects and appear to decrease early after transplantation [ 31 , 32 , 33 ]. Thus, according to our findings, subtle and possibly additive immune mechanisms might further aggravate the proinflammatory milieu of CKD in the setting of heart failure.…”

“…Furthermore, it should be noted that studies investigating NK cells in CKD patients are few, conducted in small cohorts, and have mainly analyzed NK cells in hemodialysis patients. Thus, in a previous study conducted by our group in a cohort of peritoneal dialysis patients, increased NK cells were linked to fluid overload determined either as overhydration in lung ultrasound, body composition monitor measurements, or an increased E/E’ in echocardiography [ 32 ]. As a result, further research is to clarify and specify the role of NK cells within the heterogenous pathological entities included in the CVD and CKD spectrum.…”

Identification of Genes Associated with Decreasing Abundance of Monocytes in Long-Term Peritoneal Dialysis Patients

“…In end-stage kidney disease, the altered expression of immune cells including monocyte subsets affects the modulation of immunity and inflammation. 14 Innate immune cells, monocytes, and polymorphonuclear leukocytes recognize pathogens through Toll-like receptors, which trigger phagocytosis, cell activation, and secretion of inflammatory cytokines. A study found that TLR2 and TLR4 expression were significantly up-regulated in monocytes in the end-stage kidney disease group.…”