TLR-4+ peripheral blood monocytes and cardiovascular events in patients with chronic kidney disease--a prospective follow-up study

Lorenzen, Johan M.; David, Sascha; Richter, Alena; Groot, Kirsten de; Kielstein, Jan T.; Haller, Hermann; Thum, Thomas; Fliser, Danilo

doi:10.1093/ndt/gfq758

Cited by 16 publications

(12 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With that in mind, the short lifespan of neutrophils makes the cells the best target for measuring acute and short time stimuli such as the direct effect of a single haemodialysis. Despite the fact that the number of monocytes expressing TLR/CD14 positively correlates with a high sensitivity CRP concentration (proving the prevailing inflammatory state in the haemodialysed patients [ 26 ]), we observed no significant changes in TLR4 expression on neutrophils forming the biggest population of carriers of the pro-inflammatory alarmins [ 11 ].…”

Section: Discussionmentioning

confidence: 93%

Basic inflammatory indices and chosen neutrophil receptors expression in chronic haemodialysed patients

Baj

Zbróg

Szuflet

et al. 2018

cejoi

View full text Add to dashboard Cite

Aim of the studyEnd stage renal disease (ESRD) patients on chronic haemodialysis (HD) are immuno-compromised and prone to infection. Toll-like receptors (TLRs) play a role as both primary sensors of pathogen invasion and activators of inflammatory reaction. To test if the immune impairment in HD patients is connected with the defective expression of the neutrophil TLRs, we aimed to examine their expression and chosen inflammatory indices.Material and methodsWe tested CD14, TLR4, and TLR9 expressions on neutrophils using flow cytometry. Soluble CD14, C-reactive protein (CRP), and mannose-binding lectin (MBL) concentrations were tested using the ELISA method in 31 ESRD patients on chronic haemodialysis programs and in 17 healthy control subjects.ResultsNeutrophil TLR4 and TLR9 expressions did not differ significantly compared to the controls. The ESRD patients had markedly increased CRP and sCD14 levels alongside decreased MBL concentrations and neutrophil CD14 expression. The TLR4 expression correlated well with both TLR9 and CD14 neutrophil expressions; however, the increased CRP in the blood did not correlate with the MBL concentration or TLR expression.ConclusionsThe chronic program of haemodialysis and biochemical disorders in ESRD patients result in a low-grade chronic inflammation with no significant impact on the expression of neutrophil TLR4 and TLR9.

show abstract

Section: Discussionmentioning

confidence: 93%

Basic inflammatory indices and chosen neutrophil receptors expression in chronic haemodialysed patients

Baj

Zbróg

Szuflet

et al. 2018

cejoi

View full text Add to dashboard Cite

show abstract

“…Interestingly, in a separate study, TLR4 expression in peripheral blood monocytes was evaluated in 191 patients with ESRD. 25 TLR4 expression correlated significantly with age (r = 0.2, p = 0.007), CRP (r = 0.2, p = 0.008), and mean arterial blood pressure (r = −0.2, p = 0.02).…”

Section: Discussionmentioning

confidence: 97%

Intensive Hemodialysis Preserved Cardiac injury

Chan

Valaperti

et al. 2015

ASAIO Journal

View full text Add to dashboard Cite

Cardiac injury triggers cellular responses involving both cardiomyocytes and nonmuscle cells to process cardiac structural remodeling. End-stage renal disease (ESRD), despite conventional dialysis, is associated with adverse cardiac remodeling and increased cardiovascular events. Intensification of hemodialysis with nocturnal home hemodialysis (NHD; five sessions per week; 6-8 hours per treatment) was associated with regression of left ventricular hypertrophy and downregulation of genes in apoptosis and fibrosis. In this pilot study, we hypothesize that NHD achieves its cardiac effects in part through attenuation of innate immune activation resulting in amelioration of cardiomyocytes apoptosis and fibrosis. Eight patients (4M:4F; age, 59 ± 9 years) with ESRD were studied. Half of the cohort was converted to NHD, whereas the rest of the patients were maintained on conventional hemodialysis (CHD). At baseline, CHD was associated with an increase in cardiomyocyte apoptosis detected by flow cytometry using Annexin V (mean fluorescence index in CHD and in normal control is 1.00 ± 0.05 vs. 0.66 ± 0.01, p < 0.05). After conversion to NHD, cardiomyocyte apoptosis was reduced compared with baseline CHD situation (p < 0.05) and approached that of normal control (0.59 ± 0.09 vs. 0.66 ± 0.01, p > 0.05). The CHD serum was associated with a coordinated augmentation innate immunity pathway, significantly increasing myeloid differentiation factor-88 and interleukin-1 receptor-associated kinase-4; NHD was able to reduce their levels. Heat shock protein 60 was augmented during CHD condition and fell after NHD. In addition, CHD increased fibroblast proliferation and myofibroblast transformation. Uremia is associated with activation of common innate immune signaling pathways leading to fibrosis and apoptosis. Amelioration of uremic clearance by NHD may attenuate this pathological signaling cascade.

show abstract

“…A recent study by Lorenzen et al [10] indicated that several traditional risk factors did not affect incident cardiovascular events including death in hemodialysis patients. Therefore, other factors, including free light chains, may be more important for the survival of hemodialysis patients.…”

Section: Discussionmentioning

confidence: 99%

Higher Serum Levels of Free ĸ plus λ Immunoglobulin Light Chains Ameliorate Survival of Hemodialysis Patients

Thilo

Caspari

Scholze

et al. 2011

Kidney Blood Press Res

View full text Add to dashboard Cite

Background/Aims: Impaired immune function is common in patients with chronic renal failure. Now, we determined whether serum levels of free immunoglobulin light chains predict mortality in patients with chronic kidney disease stage 5 on hemodialysis. Methods: We performed a prospective cohort study of 160 hemodialysis patients with a median follow-up of 15 months (interquartile range, 3–44 months). Serum levels of free ĸ and λ immunoglobulin light chains were measured at the start of the study. The primary end point was mortality from any cause. Results: In survivors, median serum levels of free ĸ plus λ immunoglobulin light chains were significantly higher compared with nonsurvivors (p < 0.05). Survival was significantly longer in those patients who had serum levels of free ĸ plus λ immunoglobulin light chains above the median compared with patients with serum levels below the median of 210 mg/l (χ² = 5.91; p = 0.015 by log-rank, Mantel-Cox, test). We performed univariate and multivariate regression analysis showing that older age and lower serum levels of free ĸ plus λ immunoglobulin light chains predicted mortality in hemodialysis patients. Conclusion: Higher serum levels of free ĸ plus λ immunoglobulin light chains ameliorate survival in hemodialysis patients.

show abstract

TLR-4+ peripheral blood monocytes and cardiovascular events in patients with chronic kidney disease--a prospective follow-up study

Abstract: Unexpectedly, we could not detect an association between CD14+/TLR-4+ monocytes and incident CVE as well as CV death in stable hemodialysis patients. Further studies have to clarify the potential role of this cell population for CV outcome in this population.

Cited by 16 publications

References 19 publications

Basic inflammatory indices and chosen neutrophil receptors expression in chronic haemodialysed patients

Basic inflammatory indices and chosen neutrophil receptors expression in chronic haemodialysed patients

Intensive Hemodialysis Preserved Cardiac injury

Higher Serum Levels of Free ĸ plus λ Immunoglobulin Light Chains Ameliorate Survival of Hemodialysis Patients

Contact Info

Product

Resources

About