Circulating Argonaute-Bound MicroRNA-126 Reports Vascular Dysfunction & Response to Treatment in Acute & Chronic Kidney Disease

2020 ◽  
Author(s):  
Kathleen Scullion ◽  
Bastiaan Vliegenthart ◽  
Laura Rivoli ◽  
Wilna Oosthuyzen ◽  
Tariq Farrah ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Dysfunction ◽  
Response To Treatment

scholarly journals Circulating argonaute-bound microRNA-126 reports vascular dysfunction & response to treatment in acute & chronic kidney disease

2020 ◽  
Author(s):  
Kathleen M Scullion ◽  
A D Bastiaan Vliegenthart ◽  
Laura Rivoli ◽  
Wilna Oosthuyzen ◽  
Tariq E Farrah ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Function ◽  
Clinical Decision Making ◽  
Vascular Dysfunction ◽  
Unmet Need ◽  
Post Treatment ◽  
Response To Treatment ◽  
Serum Samples ◽  
Anca Vasculitis

Background: Vascular and kidney dysfunction commonly co-exist. There is an unmet need for biomarkers of vascular health. Circulating microRNAs (miRs) are disease biomarkers; miR-126 is endothelial cell-enriched. We measured circulating miR-126 in rats with nephrotoxic nephritis (NTN) and humans with acute endothelial and renal injury (vasculitis associated with autoantibodies to neutrophil cytoplasm antigens (ANCA)). We then compared these findings to those from patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), and explored the relationship between miR-126 and markers of vascular dysfunction. Methods: In rats, NTN was induced with nephrotoxic serum. Samples were prospectively collected from 70 patients with ANCA vasculitis (at presentation and once in treatment-induced remission), healthy subjects (n=60), patients with CKD (n=30) and ESRD before and after dialysis (n=15). In humans and rats, miR-126 and miR-122 (liver-specific control) were measured and correlated with vascular function. Results: In NTN rats, miR-126 was selectively reduced. In ANCA vasculitis, pre-treatment circulating miR-126 was reduced compared to health (88-fold reduction, ROC-AUC 0.87 (0.80-0.94)). miR-126 increased 3.4-fold post-treatment but remained lower than in health (~26-fold). There was no change in miR-122. Plasma fractionation demonstrated that argonaute 2-bound miR-126 increased with treatment of ANCA vasculitis. Urinary miR-126 decreased post-treatment. miR-126 did not differ between CKD and health but its concentration significantly correlated with measures of endothelial dysfunction. miR-126 was substantially reduced in ESRD (~350 fold compared to health and CKD). Conclusions: miR-126 may be a marker of vascular inflammation and has the potential to aid in clinical decision-making.

scholarly journals Circulating Endothelial Cells and Chronic Kidney Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kunying Zhang ◽  
Fang Yin ◽  
Lin Lin
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Vascular Dysfunction ◽  
Endothelial Damage ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Term Outcome ◽  
Long Term Outcome

Endothelial dysfunction may play a crucial role in initiation of the pathogenesis of vascular disease and atherosclerosis. The identification and quantification of circulating endothelial cells (CEC) have been developed as a novel marker of endothelial function. We describe, in great detail, mechanisms of endothelial dysfunction and CEC detachment. We also review the relationship between numbers of CEC and disease severity and response to treatment. In addition, we describe the possible clinical use of CEC in chronic kidney disease (CKD) and kidney transplantation. In summary, CEC have been developed as a novel approach to assess the endothelial damage. Measurement of the CEC level would provide an important diagnostic and prognostic value on the endothelium status and the long-term outcome of vascular dysfunction.

scholarly journals A Systematic Review and Meta-Analysis of Pharmacogenetic Studies in Patients with Chronic Kidney Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4480
Author(s):  
Maria Tziastoudi ◽  
Georgios Pissas ◽  
Georgios Raptis ◽  
Christos Cholevas ◽  
Theodoros Eleftheriadis ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Meta Analysis ◽  
Public Health Problem ◽  
Response To Treatment ◽  
Genotype Distribution ◽  
Global Public Health ◽  
High Prevalence ◽  
Additive Inheritance

Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. In an effort to elucidate the contribution of genetic variants located in several genes in the response to treatment of patients with CKD, we performed a systematic review and meta-analysis of all available pharmacogenetics studies. The association between genotype distribution and response to medication was examined using the dominant, recessive, and additive inheritance models. Subgroup analysis based on ethnicity was also performed. In total, 29 studies were included in the meta-analysis, which examined the association of 11 genes (16 polymorphisms) with the response to treatment regarding CKD. Among the 29 studies, 18 studies included patients with renal transplantation, 8 involved patients with nephrotic syndrome, and 3 studies included patients with lupus nephritis. The present meta-analysis provides strong evidence for the contribution of variants harbored in the ABCB1, IL-10, ITPA, MIF, and TNF genes that creates some genetic predisposition that reduces effectiveness or is associated with adverse events of medications used in CKD.

scholarly journals Biomarker Profiling of Neurovascular Diseases in Patients with Stage 5 Chronic Kidney Disease

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 248S-254S
Author(s):  
Justin Lee ◽  
Jack Bontekoe ◽  
Brandon Trac ◽  
Vinod Bansal ◽  
José Biller ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Carotid Artery Disease ◽  
Vascular Dysfunction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neurocognitive Deficits ◽  
Intracranial Atherosclerotic Disease ◽  
Artery Disease ◽  
D Dimer ◽  
Neurovascular Diseases

Patients with stage 5 chronic kidney disease (CKD5D) have a higher risk of developing neurocognitive deficits. Stroke, cervical carotid artery disease (CCAD), and intracranial atherosclerotic disease (ICAD) are causes of such deficits in CKD5D. Chronic inflammation from renal failure elevates risk for these diseases through oxidative stress and vascular dysfunction. The adverse impact on the carotid and intracranial vasculatures contributes to the multifactorial pathophysiology of stroke. Eleven plasma biomarker levels in patients with CKD5D (n = 97) and healthy controls (n = 17-50) were measured using sandwich enzyme-linked immunosorbent assay (ELISA) method. Of the 97 patients with CKD5D, 24 had CCAD, 19 had ICAD, and 23 had acute stroke. Elevations in NACHT, LRR, and PYD domains-containing protein 3 (NALP3) levels in patients with CKD5D (+)CCAD (1.80 ± 0.11 ng/mL) compared to patients with (−)CCAD (1.55 ± 0.08 ng/mL) were statistically significant ( P = .0299). Differences in D-dimer levels were also found to be statistically significant ( P = .0258) between CKD5D (+)stroke (1.83 ± 0.42 μg/mL) and (−)stroke (0.89 ± 0.13 μg/mL) groups. The ages of the (+) neurovascular disease groups were found to be significantly elevated compared to the (−) neurovascular disease groups ( P = .0002 carotid AD; P < .0001 ICAD; P = .0157 stroke). D-dimer levels were positively correlated with age in CKD5D ( P = .0375). With the possible exception of NALP3 for CCAD, profiling levels of specific biomarkers for risk stratification of neurovascular diseases in the CKD5D population warrants further investigation.

Abstract 16926: The Effects of a Mitochondrial Targeted Ubiquinone (MitoQ) on Vascular Function in Chronic Kidney Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Danielle L Kirkman ◽  
Ninette Shenouda ◽  
Joseph M Stock ◽  
Bryce J Muth ◽  
Nicholas Chouramanis ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Brachial Artery ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Aortic Pressure ◽  
Double Blind ◽  
Reflected Waves ◽  
Arterial Hemodynamics ◽  
Artery Flow

Introduction: Aberrant vascular function contributes to the substantially high cardiovascular burden of chronic kidney disease (CKD). Mitochondrial derived oxidative stress is a potential therapeutic target to ameliorate CKD related vascular dysfunction. Hypothesis: We hypothesized that a mitochondrial targeted antioxidant (MitoQ) would improve vascular function in Stage 3-5 CKD patients without overt cardiovascular disease. Methods: In this controlled, double-blind trial, 18 CKD patients (Mean±SEM: Age, 62±3 years; eGFR, 45±3 ml•min•1.73 2 ) were randomized to receive an oral dose of MitoQ (20mg/day; MTQ) or a Placebo (PLB) for 4 weeks. Outcome measures were assessed at week 0 and week 4. Aortic pressure waves were synthesized from brachial artery waveforms acquired by oscillometry and the use of a generalized transfer function. The central pressure waveform was separated into forward and reflected waves using a triangular flow waveform. Conduit artery vascular function was assessed via brachial artery flow mediated dilation (FMD). Results: MitoQ was well tolerated and patient compliance was high (MTQ, 99.6±0.4%; PLB, 97.8±2.2%). Independent of peripheral (Baseline vs. Follow Up: MTQ, 140±6 vs. 137±6 mmHg; PLB, 136±4 vs. 134±6 mmHg; interaction p=0.7) and central (MTQ, 128±5 vs. 123±6 mmHg; PLB, 124±3 vs. 123±5 mmHg; interaction p=0.8) systolic blood pressures, MitoQ maintained forward wave amplitudes (MTQ, 31±3 vs. 29±1 mmHg; PLB, 29±3 vs. 36±3 mmHg; interaction p=0.05) and tended to reduce reflected wave amplitudes (MTQ, 18±2 vs. 16±1 mmHg; PLB, 19±2 vs. 21±2 mmHg; interaction p=0.04). MitoQ administration favored improvements in FMD (MTQ, 2.4±0.3 vs. 4.0±0.9%; PLB, 4.2±1.0 vs. 2.5±1.0%; interaction p=0.04). Conclusions: These results suggest that targeting mitochondrial derived reactive oxygen species holds promise as a potential therapeutic strategy to improve CKD related vascular dysfunction. Whether MitoQ related improvements in arterial hemodynamics are a result of augmented cardiac function or a reduction in vascular resistance warrants future investigation in larger studies.

scholarly journals Coronary Vascular Dysfunction and Prognosis in Patients With Chronic Kidney Disease

2012 ◽  
Vol 5 (10) ◽  
pp. 1025-1034 ◽  
Author(s):  
Venkatesh L. Murthy ◽  
Masanao Naya ◽  
Courtney R. Foster ◽  
Jon Hainer ◽  
Mariya Gaber ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Dysfunction

scholarly journals Vascular dysfunction and atherosclerosis in chronic kidney disease; A distinct entity

2019 ◽  
Vol 8 (2) ◽  
pp. 17-17 ◽  
Author(s):  
Eranga Harshani Silva ◽  
Chandima Madhu Wickramatilake ◽  
Sarath Lekamwasam ◽  
Lakmini Kumari Boralugoda Mudduwa ◽  
Ranjuka Arushana Ubayasiri
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Dysfunction ◽  
Therapeutic Interventions ◽  
Cvd Risk ◽  
Unexplored Area ◽  
Calcium And Phosphate Metabolism ◽  
Conventional Risk Factors

Cardiovascular disease (CVD) is prevalent among patients with chronic kidney disease (CKD) and its occurrence and severity cannot be fully defined by the conventional cardiovascular risk factors namely age, hypertension, dyslipidaemia, diabetes mellitus and obesity. Contemporary studies have examined the role of non-conventional risk factors such as anemia, hyperhomocysteinemia, calcium and phosphate metabolism, vascular stiffness due to endothelial dysfunction ( ED), oxidative injury, and inflammation in the causation of CVD in CKD. Therapeutic interventions used in non-CKD patients are found to be less effective on patients with CKD. The purpose of this review was to gather available evidence on the CVD risk among CKD patients. Numerous mechanisms have been postulated to describe the increased atherogenicity in CKD patients. We discuss these mechanisms especially arterial stiffness, ED and inflammation in detail. In conclusion, CVD in CKD is still an unexplored area which needs further studies to uncover the possible mechanisms. Identifying newer therapies to improve health among this group of patients is of paramount importance.

scholarly journals Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential Therapeutic Role of Exercise

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ulf G. Bronas ◽  
Houry Puzantian ◽  
Mary Hannan
Keyword(s):  
Quality Of Life ◽  
Chronic Kidney Disease ◽  
Cognitive Impairment ◽  
Kidney Disease ◽  
Physical Function ◽  
Vascular Dysfunction ◽  
Therapeutic Modality ◽  
Increased Risk

Chronic kidney disease (CKD) is considered a model of accelerated aging. More specifically, CKD leads to reduced physical functioning and increased frailty, increased vascular dysfunction, vascular calcification and arterial stiffness, high levels of systemic inflammation, and oxidative stress, as well as increased cognitive impairment. Increasing evidence suggests that the cognitive impairment associated with CKD may be related to cerebral small vessel disease and overall impairment in white matter integrity. The triad of poor physical function, vascular dysfunction, and cognitive impairment places patients living with CKD at an increased risk for loss of independence, poor health-related quality of life, morbidity, and mortality. The purpose of this review is to discuss the available evidence of cerebrovascular-renal axis and its interconnection with early and accelerated cognitive impairment in patients with CKD and the plausible role of exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis pathophysiological link and its interconnection with physical function is important for clinicians in order to minimize the risk of loss of independence and improve quality of life in patients with CKD.

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