The Protective Role of Klotho in CKD-Associated Cardiovascular Disease DOI Creative Commons
Xianjin Bi, Ke Yang, Bo Zhang

et al.

Kidney Diseases, Journal Year: 2020, Volume and Issue: 6(6), P. 395 - 406

Published: Jan. 1, 2020

<b><i>Background:</i></b> Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in advanced CKD. The major pathological changes CKD-associated CVD severe vascular media calcification, aberrant cardiac remodeling such as hypertrophy fibrosis, well accelerated atherosclerosis. α-Klotho is proposed an anti-aging gene, which primarily expressed kidney. Recent studies reveal that deficiency associated with profound cardiovascular dysfunction. Of note, CKD represents extremely declined levels, hinting may be implicated pathogenesis CVD. <b><i>Summary:</i></b> Based on pathogenic mechanism decreased Klotho levels circulation even early stage 1 CKD, serves a sensitive biomarker for renal insufficiency also novel predictor risk overall events Meanwhile, loss resulted from kidney dysfunction markedly contributes to progressive development By contrast, prevention decline using exogenous supplementation or genetically activated ways by several mechanisms can dramatically mitigate dysfunction, prevent retard progression CKD-accelerated <b><i>Key Messages:</i></b> predictive contributor In future, crucial potential therapeutic strategy decrease burden comorbidity clinics.

Language: Английский

Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease DOI Creative Commons
LaTonya J. Hickson, Larissa Prata, Shane A. Bobart

et al.

EBioMedicine, Journal Year: 2019, Volume and Issue: 47, P. 446 - 456

Published: Sept. 1, 2019

Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing at etiological sites in multiple chronic diseases. Senolytics, including combination of Dasatinib Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks defend them against their own apoptotic environment. In first clinical trial senolytics, D Q improved physical function patients idiopathic pulmonary fibrosis (IPF), a fatal disease, but to date, no peer-reviewed study has directly demonstrated senolytics decrease humans.In an open label Phase 1 pilot study, we administered 3 days oral 100 mg 1000 subjects diabetic kidney disease (N = 9; 68·7 ± 3·1 years old; 2 female; BMI:33·9 2·3 kg/m2; eGFR:27·0 2·1 mL/min/1·73m2). Adipose tissue, skin biopsies, blood were collected before 11 after completing senolytic treatment. cell macrophage/Langerhans markers circulating SASP assayed.D reduced adipose tissue burden within days, decreases p16INK4A-and p21CIP1-expressing β-galactosidase activity, adipocyte progenitors limited replicative potential. macrophages, are attracted, anchored, activated crown-like structures decreased. Skin epidermal p16INK4A+ p21CIP1+ reduced, as factors, IL-1α, IL-6, MMPs-9 -12."Hit-and-run" treatment case have elimination half-lives <11 h, significantly humans. FUND: NIH Foundations. ClinicalTrials.gov Identifier: NCT02848131. Senescence, Frailty, Mesenchymal Stem Cell Functionality Chronic Kidney Disease: Effect Senolytic Agents.

Language: Английский

Citations

978
Food as medicine: targeting the uraemic phenotype in chronic kidney disease DOI
Denise Mafra, Natália A. Borges, Bengt Lindholm

et al.

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 17(3), P. 153 - 171

Published: Sept. 22, 2020

Language: Английский

Citations

186
Inflammation and Premature Ageing in Chronic Kidney Disease DOI Creative Commons
Thomas Ebert, Sven‐Christian Pawelzik,

Anna Witasp

et al.

Toxins, Journal Year: 2020, Volume and Issue: 12(4), P. 227 - 227

Published: April 4, 2020

Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype contribute to impaired health status, reduced quality life, mortality in chronic kidney disease (CKD). Because there is a huge global burden due CKD, treatment strategies targeting CKD particular interest. Several distinct features may represent potential options attenuate risk progression poor outcome CKD. The nuclear factor erythroid 2-related 2 (NRF2)–kelch-like cell-derived protein with CNC homology [ECH]-associated 1 (KEAP1) signaling pathway, endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, mitochondrial biogenesis currently most promising candidates, different pharmaceutical compounds already under evaluation. If studies humans show beneficial effects, carefully phenotyped patients can benefit from them.

Language: Английский

Citations

183
Endothelial Cell Dysfunction and Increased Cardiovascular Risk in Patients With Chronic Kidney Disease DOI Creative Commons
Constance C. F. M. J. Baaten, Sonja Vondenhoff, Heidi Noels

et al.

Circulation Research, Journal Year: 2023, Volume and Issue: 132(8), P. 970 - 992

Published: April 13, 2023

The endothelium is considered to be the gatekeeper of vessel wall, maintaining and regulating vascular integrity. In patients with chronic kidney disease, protective endothelial cell functions are impaired due proinflammatory, prothrombotic uremic environment caused by decline in function, adding increase cardiovascular complications this vulnerable patient population. review, we discuss functioning healthy conditions contribution dysfunction disease. Further, summarize phenotypic changes disease relation risk We also review mechanisms that underlie consider potential pharmacological interventions can ameliorate health.

Language: Английский

Citations

74
Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence DOI Creative Commons
Julia Carracedo, Matilde Alique, Carmen Vida

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: March 20, 2020

Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is condition affecting approximately 10% general population. The prevalence has increased over past decades because aging population worldwide. Indeed, CVDs constitute premature form CVD observed Multiple studies indicate that renal undergo accelerated aging, which precipitates appearance pathologies, including CVDs, usually associated advanced age. In this review, we discuss several aspects characterize CKD-associated etiopathogenic elements share population, changes cellular balance reactive oxygen species (ROS), senescence. Uremia-associated linked numerous at molecular level. These are similar to normal physiologic aging. We also new perspectives study epigenetic alterations intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), promote vascular damage subsequent development CVD. Understanding processes factors involved senescence other abnormal signaling will identify therapeutic targets lead improved methods diagnosis monitoring for CVDs.

Language: Английский

Citations

102
Inflammation and Oxidative Stress in Chronic Kidney Disease and Dialysis Patients DOI
Thomas Ebert, Ognian Neytchev,

Anna Witasp

et al.

Antioxidants and Redox Signaling, Journal Year: 2021, Volume and Issue: 35(17), P. 1426 - 1448

Published: May 19, 2021

Significance: Chronic kidney disease (CKD) can be regarded as a burden of lifestyle that shares common underpinning features and risk factors with the aging process; it is complex constituted by several adverse components, including chronic inflammation, oxidative stress, early vascular aging, cellular senescence. Recent Advances: A systemic approach to tackle CKD, based on mitigating associated inflammatory, cell damage processes, has potential attenuate effects but also preempts development progression morbidities. In effect, this will enhance health span compress period morbidity. Pharmacological, nutritional, potentially lifestyle-based interventions are promising therapeutic avenues achieve such goal. Critical Issues: present review, currents concepts inflammation key patho-mechanisms in CKD addressed. particular, beneficial different patients discussed. Future Directions: Senotherapeutics, nuclear factor erythroid 2-related 2-kelch-like ECH-associated protein 1 (NRF2-KEAP1) signaling pathway, endocrine klotho axis, inhibitors sodium-glucose cotransporter 2 (SGLT2), live bio-therapeutics have reduce improve quality life, well morbidity mortality, fragile high-risk patient group. Antioxid. Redox Signal. 35, 1426-1448.

Language: Английский

Citations

101
Frailty, aging, and periodontal disease: Basic biologic considerations DOI

Daniel Clark,

Eftychia Kotronia, Sheena E Ramsay

et al.

Periodontology 2000, Journal Year: 2021, Volume and Issue: 87(1), P. 143 - 156

Published: Aug. 31, 2021

Aging is associated with the development of disease. Periodontal disease one many diseases and conditions that increase in prevalence age. In addition to traditional focus on individual age-related conditions, there now a greater recognition multisystem such as frailty play an important role health older populations. Frailty clinical condition adults increases risk adverse outcomes. Both periodontal are common chronic populations share several factors. There likely bidirectional relationship between frailty. Comorbid systemic diseases, poor physical functioning, limited ability self-care frail people have been implicated underlying association addition, both also strong associations inflammatory dysregulation other pathophysiologic changes may similarly underlie their progression. Investigating immune cells regulate inflammation lead better understanding could therapeutic targets for improved management

Language: Английский

Citations

95
Novel treatment strategies for chronic kidney disease: insights from the animal kingdom DOI
Peter Stenvinkel, Johanna Painer, Makoto Kuro‐o

et al.

Nature Reviews Nephrology, Journal Year: 2018, Volume and Issue: 14(4), P. 265 - 284

Published: Jan. 15, 2018

Language: Английский

Citations

91
Inflammation: a putative link between phosphate metabolism and cardiovascular disease DOI Creative Commons
Jakob Voelkl, Daniela Egli-Spichtig, Ioana Alesutan

et al.

Clinical Science, Journal Year: 2021, Volume and Issue: 135(1), P. 201 - 227

Published: Jan. 1, 2021

Abstract Dietary habits in the western world lead to increasing phosphate intake. Under physiological conditions, extraosseous precipitation of with calcium is prevented by a mineral buffering system composed calcification inhibitors and tight control serum levels. The coordinated hormonal regulation involves fibroblast growth factor 23 (FGF23), αKlotho, parathyroid hormone (PTH) calcitriol. A severe derangement homeostasis observed patients chronic kidney disease (CKD), patient collective extremely high risk cardiovascular morbidity mortality. Higher levels have been associated increased for (CVD) CKD patients, but also general population. causal connections between CVD are currently incompletely understood. An assumed link development medial vascular calcification, process actively promoted regulated complex mechanistic interplay involving activation pro-inflammatory signalling. Emerging evidence indicates disturbances inflammation. present review focuses on critical interactions homeostasis, inflammation, CVD. Especially, responses mediating hyperphosphatemia-related as well FGF23 inflammation alterations, beyond its phosphaturic effects, addressed.

Language: Английский

Citations

59
Chronic Kidney Disease and Arterial Stiffness: A Two-Way Path DOI Creative Commons
Felipe Inserra,

Pedro Forcada,

Agustina Castellaro

et al.

Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 8

Published: Nov. 23, 2021

The kidney-heart relationship has raised interest for the medical population since its vast and complex interaction significantly impacts health. Chronic kidney disease (CKD) generates vascular structure function changes, with significant hemodynamic effects. early arterial stiffening in CKD patients is a consequence of between oxidative stress chronic inflammation, leading to an accelerated deterioration left ventricular alteration tissue perfusion. amplifies inflammatory cascade's activation responsible altering endothelium function, increasing tone, wall thickening, favors calcium deposits wall. Simultaneously, autonomic imbalance, other hormonal systems, also favor overactivation fibrotic mediators. Thus, disarrangement contributes structural functional lesions throughout On hand, rise volume overload high afterload. It increases burden consequent myocardial remodeling, development hypertrophy and, turn, heart failure. noteworthy that reduction glomerular mass renal diseases compensatory filtration overdriven associated large-arteries stiffness cardiovascular events. Furthermore, we consider alterations system's mechanical properties are crucial perfusion, mainly low resistance. knowledge these processes may help reader integrate them from pathophysiological perspective, providing comprehensive idea this two-way path dysfunction their impact at level.

Language: Английский

Citations

57