Cardiovascular Risks of Hypertension: Lessons from Children with Chronic Kidney Disease DOI Creative Commons
You‐Lin Tain, Chien‐Ning Hsu

Children, Journal Year: 2022, Volume and Issue: 9(11), P. 1650 - 1650

Published: Oct. 28, 2022

Hypertension is the most common complication of chronic kidney disease (CKD) in children, having a strong association with subsequential cardiovascular (CVD). In pediatric CKD, considerable percentage children hypertension are undiagnosed or undertreated. Prior research has evaluated structural and functional markers subclinical CVD biomarkers adults while ideal pediatrics still insufficiently studied. The ultimate goal this review to summarize what currently known about state hypertension, risk factors, potential markers/biomarkers pre-dialysis CKD. We discuss omics-related pathophysiologic processes endothelial dysfunction, injury, oxidative stress inflammation that classified by specific biomarkers. Moreover, we illustrate existing challenges highlight paucity CKD evaluate these for future clinical practice. Thus, achieving utility use remains significant challenge requiring additional efforts.

Language: Английский

Investigation of a targeted panel of gut microbiome–derived toxins in children with chronic kidney disease DOI
Mina Ebrahimi, Stephen R. Hooper, Mark Mitsnefes

et al.

Pediatric Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Language: Английский

Citations

2
Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance DOI Open Access
Johannes Holle, Hendrik Bartolomaeus, Ulrike Löber

et al.

Journal of the American Society of Nephrology, Journal Year: 2022, Volume and Issue: 33(12), P. 2259 - 2275

Published: Aug. 19, 2022

CKD is characterized by a sustained proinflammatory response of the immune system, promoting hypertension and cardiovascular disease. The underlying mechanisms are incompletely understood but may be linked to gut dysbiosis. Dysbiosis has been described in adults with CKD; however, comorbidities limit CKD-specific conclusions.We analyzed fecal microbiome, metabolites, phenotypes 48 children (with normal kidney function, stage G3-G4, G5 treated hemodialysis [HD], or transplantation) mean±SD age 10.6±3.8 years.Serum TNF-α sCD14 were stage-dependently elevated, indicating inflammation, barrier dysfunction, endotoxemia. We observed compositional functional alterations including diminished production short-chain fatty acids. Plasma metabolite analysis revealed stage-dependent increase tryptophan metabolites bacterial origin. Serum from patients on HD activated aryl hydrocarbon receptor stimulated monocytes, corresponding shift classic nonclassic intermediate monocytes. Unsupervised T cells loss mucosa-associated invariant (MAIT) regulatory cell subtypes HD.Gut dysfunction microbial imbalance apparently mediate phenotype, thereby driving susceptibility data highlight importance microbiota-immune axis CKD, irrespective confounding comorbidities.

Language: Английский

Citations

39
Faecal Microbiota Transplantation and Chronic Kidney Disease DOI Open Access
Ji Bian, Ann Liebert, Brian Bicknell

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(12), P. 2528 - 2528

Published: June 17, 2022

Faecal microbiota transplantation (FMT) has attracted increasing attention as an intervention in many clinical conditions, including autoimmune, enteroendocrine, gastroenterological, and neurological diseases. For years, FMT been effective second-line treatment for Clostridium difficile infection (CDI) with beneficial outcomes. is also promising improving bowel diseases, such ulcerative colitis (UC). Pre-clinical studies suggest that this microbiota-based may influence the development progression of chronic kidney disease (CKD) via modifying a dysregulated gut–kidney axis. Despite high morbidity mortality due to CKD, there are limited options until end-stage occurs, which results death, dialysis, or transplantation. This imposes significant financial health burden on individual, their families careers, system. Recent have suggested strategies reverse gut dysbiosis using therapy CKD. review summarises preclinical evidence postulates potential therapeutic effect management

Language: Английский

Citations

36
Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease DOI Creative Commons
Fernanda Guedes Rodrigues, Milene Subtil Ormanji, Ita Pfeferman Heilberg

et al.

European Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 51(9)

Published: May 5, 2021

Abstract Deregulations in gut microbiota may play a role vascular and bone disease chronic kidney (CKD). As glomerular filtration rate declines, the colon becomes more important as site of excretion urea uric acid, an increased bacterial proteolytic fermentation alters microbial balance. A diet with limited amounts fibre, well certain medications (eg phosphate binders, iron supplementation, antibiotics) further contribute to changes composition among CKD patients. At same time, both calcification are common patients advanced disease. This narrative review describes emerging evidence on dysbiosis, calcification, demineralization their interrelationship termed ‘gut‐bone‐vascular axis’ progressive CKD. The diet, metabolites (ie indoxyl sulphate, p‐cresyl trimethylamine N‐oxide (TMAO) short‐chain fatty acids (SCFA)), vitamin K deficiency, inflammatory cytokines impact health discussed. framework open up novel preventive therapeutic approaches targeting microbiome attempt improve cardiovascular

Language: Английский

Citations

33
Uremic Toxin Indoxyl Sulfate Promotes Macrophage-Associated Low-Grade Inflammation and Epithelial Cell Senescence DOI Open Access

Andrea Ribeiro,

Feiyue Liu,

Matthias Srebrzynski

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8031 - 8031

Published: April 28, 2023

In this study, we investigated the impact of uremic toxin indoxyl sulfate on macrophages and tubular epithelial cells its role in modulating response to lipopolysaccharide (LPS). Indoxyl accumulates blood patients with chronic kidney disease (CKD) is a predictor overall cardiovascular morbidity/mortality. To simulate condition, primary were incubated at low concentrations as well found patients, both alone upon LPS challenge. The results showed that induced release reactive oxygen species low-grade inflammation macrophages. Moreover, combined (proinflammatory conditions), significantly increased TNF-α, CCL2, IL-10 but did not affect polarization Pre-treatment following challenge expression aryl hydrocarbon receptor (Ahr) NADPH oxidase 4 (Nox4) which generate (ROS). Further, experiments revealed might induce senescence parenchymal therefore participate progression inflammaging. conclusion, study provides evidence provokes inflammation, modulates macrophage function, enhances inflammatory associated LPS. Finally, signaling contributes during injury.

Language: Английский

Citations

16
New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease DOI Creative Commons

Lucie Hénaut,

Alexandre Candellier,

Cédric Boudot

et al.

Toxins, Journal Year: 2019, Volume and Issue: 11(9), P. 529 - 529

Published: Sept. 12, 2019

Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney (CKD), and cardiovascular calcification (CVC) one the strongest predictors CVD this population. results from complex cellular interactions involving endothelium, vascular/valvular cells (i.e., vascular smooth muscle cells, valvular interstitial resident fibroblasts), monocyte-derived macrophages. Indeed, production pro-inflammatory cytokines oxidative stress by macrophages responsible for osteogenic transformation mineralization cells. However, monocytes/macrophages show ability to modify their phenotype, consequently functions, when facing environmental modifications. This plasticity complicates efforts understand pathogenesis CVC—particularly a CKD setting, where both uraemic toxins treatment may affect monocyte/macrophage functions thereby influence CVC. Here, we review (i) mechanisms which each subset either promotes or prevents CVC, (ii) how therapies might these functions.

Language: Английский

Citations

43
Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children DOI Creative Commons
Johannes Holle, Marietta Kirchner, Jürgen G. Okun

et al.

PLoS ONE, Journal Year: 2020, Volume and Issue: 15(10), P. e0240446 - e0240446

Published: Oct. 27, 2020

The uremic toxins indoxyl sulfate (IS) and p-cresyl (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism decline renal excretion. Despite solid experimental evidence for nephrotoxic effects, the impact on progression CKD has not been investigated representative patient cohorts. In this analysis, IS pCS serum concentrations were measured 604 pediatric participants (mean eGFR 27 ± 11 ml/min/1.73m2) at enrolment into prospective Cardiovascular Comorbidity Children study. Associations analyzed by Kaplan-Meier analyses Cox proportional hazard models. During median follow up time 2.2 years (IQR 4.3-0.8 years), composite survival endpoint, defined 50% loss eGFR, or <10ml/min/1.73m2 start replacement therapy, was reached 360 (60%). Median shorter levels highest versus lowest quartile both (1.5 years, 95%CI [1.1,2.0] 6.0 [5.0,8.4]) (1.8 [1.5,2.8] 4.4 [3.4,6.0]). Multivariable regression disclosed significant association IS, but pCS, survival, which independent other risk factors including baseline proteinuria blood pressure. exploratory analysis we provide first data showing children, known factors. absence comorbidities, interfere toxins, such diabetes, obesity metabolic syndrome, these results highlight important role accentuate unmet need effective elimination strategies to lower toxin burden abate CKD.

Language: Английский

Citations

32
Pathophysiology and consequences of arterial stiffness in children with chronic kidney disease DOI
Karolis Ažukaitis, Augustina Jankauskienė, Franz Schaefer

et al.

Pediatric Nephrology, Journal Year: 2020, Volume and Issue: 36(7), P. 1683 - 1695

Published: Sept. 7, 2020

Language: Английский

Citations

30
Gut-derived metabolites as treatment targets in chronic kidney disease—an avenue toward personalized medicine DOI Creative Commons
Johannes Holle, Hendrik Bartolomaeus

Pediatric Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Language: Английский

Citations

0
Circulating Extracellular Vesicles as Putative Mediators of Cardiovascular Disease in Paediatric Chronic Kidney Disease DOI Creative Commons
Felix Behrens, Johannes Holle, Chia‐Yu Chen

et al.

Journal of Extracellular Vesicles, Journal Year: 2025, Volume and Issue: 14(3)

Published: March 1, 2025

Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney (CKD). However, pathogenesis CVD CKD remains incompletely understood. Endothelial extracellular vesicles (EC-EVs) have previously been associated with CVD. We hypothesized that alters EV release and cargo, subsequently promoting vascular remodelling. recruited 94 children CKD, including patients after transplantation healthy donors, performed phenotyping functional analyses absence age-related comorbidities. Plasma EC-EVs were increased haemodialysis decreased transplantation. Thirty microRNAs less abundant total plasma EVs predicted importance angiogenesis smooth muscle cell proliferation. In vitro, induced transcriptomic changes pathways functionally impaired angiogenic properties, migration proliferation ECs. High shear stress, as generated by arterio-venous fistulas, uremic toxins considered potential drivers release, but only combination generation from venous The resulting recapitulated miRNA observed vivo. conclusion, results altered profiles anti-angiogenic which may mediate pathology CKD. their cargo represent future therapeutic targets to attenuate

Language: Английский

Citations

0