scholarly journals Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease

2020 ◽  
Vol 13 (5) ◽  
pp. 753-757
Author(s):  
Raul Fernandez-Prado ◽  
Maria Vanessa Perez-Gomez ◽  
Alberto Ortiz
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Messenger Rna ◽  
Controlled Trial ◽  
Good News ◽  
Phase 2 ◽  
Phase 3 ◽  
Lipoprotein A ◽  
Increased Risk

Abstract Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) and statins may not be protective in advanced CKD. The reasons for the limited efficacy of statins in advanced CKD are unclear, but statins may increase plasma levels of the highly atherogenic molecule lipoprotein(a), also termed Lp(a), as well as PCSK9 (protein convertase subtilisin/kexin type 9) levels. Lp(a) has also been linked to calcific aortic stenosis, which is common in CKD. Moreover, circulating Lp(a) levels increase in nephrotic syndrome with declining renal function and are highest in patients on peritoneal dialysis. Thus, the recent publication of the Phase 2 randomized controlled trial of pelacarsen [also termed AKCEA-APO(a)-LRx and TQJ230], a hepatocyte-directed antisense oligonucleotide targeting the LPA gene messenger RNA, in persons with CVD should be good news for nephrologists. Pelacarsen safely and dose-dependently decreased Lp(a) levels by 35–80% and a Phase 3 trial [Lp(a)HORIZON, NCT04023552] is planned to run from 2020 to 2024. Unfortunately, patients with estimated glomerular filtration rate <60 mL/min or urinary albumin:creatinine ratio >100 mg/g were excluded from Phase 2 trials and those with ‘significant kidney disease’ will be excluded from the Phase 3 trial. Optimized exclusion criteria for Lp(a)HORIZON would provide insights into the role of Lp(a) in CVD in CKD patients.

scholarly journals The Role of Gut Dysbiosis in the Bone–Vascular Axis in Chronic Kidney Disease

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 285 ◽  
Author(s):  
Pieter Evenepoel ◽  
Sander Dejongh ◽  
Kristin Verbeke ◽  
Bjorn Meijers
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
Gut Dysbiosis ◽  
Increased Risk ◽  
Fermentation Pattern

Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. This contradictory association is commonly referred to as the ‘calcification paradox’ or the bone–vascular axis. Mounting evidence indicates that CKD-associated gut dysbiosis may be involved in the pathogenesis of the bone–vascular axis. A disrupted intestinal barrier function, a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, and a decreased generation of vitamin K may, alone or in concert, drive a vascular and skeletal pathobiology in CKD patients. A better understanding of the role of gut dysbiosis in the bone–vascular axis may open avenues for novel therapeutics, including nutriceuticals.

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.

scholarly journals Toll-Like Receptors in Acute Kidney Injury

2021 ◽  
Vol 22 (2) ◽  
pp. 816
Author(s):  
Cristina Vázquez-Carballo ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
Sandra Rayego-Mateos ◽  
Lucas Opazo-Ríos ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Pathological Condition ◽  
Kidney Injury ◽  
Preclinical Studies ◽  
Toll Like Receptors ◽  
Middle Income ◽  
Increased Risk

Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.

scholarly journals Prognostic Value of Soluble Suppression of Tumorigenicity 2 in Chronic Kidney Disease Patients: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guangying Guo ◽  
Aoran Huang ◽  
Xin Huang ◽  
Tianhua Xu ◽  
Li Yao
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Sample Size ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Prognostic Role ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Cvd Mortality

Objective. Previous studies have controversial results about the prognostic role of soluble suppression of tumorigenicity 2 (sST2) in chronic kidney disease (CKD). Therefore, we conduct this meta-analysis to access the association between sST2 and all-cause mortality, cardiovascular disease (CVD) mortality, and CVD events in patients with CKD. Methods. The publication studies on the association of sST2 with all-cause mortality, CVD mortality, and CVD events from PubMed and Embase were searched through August 2020. We pooled the hazard ratio (HR) comparing high versus low levels of sST2 and subgroup analysis based on treatment, continent, and diabetes mellitus (DM) proportion, and sample size was also performed. Results. There were 15 eligible studies with 11,063 CKD patients that were included in our meta-analysis. Elevated level of sST2 was associated with increased risk of all-cause mortality (HR 2.05; 95% confidence interval (CI), 1.51–2.78), CVD mortality (HR 1.68; 95% CI, 1.35–2.09), total CVD events (HR 1.88; 95% CI, 1.26–2.80), and HF (HR 1.35; 95% CI, 1.11–1.64). Subgroup analysis based on continent, DM percentage, and sample size showed that these factors did not influence the prognostic role of sST2 levels to all-cause mortality. Conclusions. Our results show that high levels of sST2 could predict the all-cause mortality, CVD mortality, and CVD events in CKD patients.

scholarly journals Alteration of the platelet transcriptome in chronic kidney disease

2012 ◽  
Vol 108 (10) ◽  
pp. 605-615 ◽  
Author(s):  
Hélène Plé ◽  
Manon Maltais ◽  
Aurélie Corduan ◽  
Guy Rousseau ◽  
François Madore ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Messenger Rna ◽  
Platelet Reactivity ◽  
Chronic Haemodialysis ◽  
Platelet Response ◽  
Transfer Protein ◽  
Stage 4 ◽  
Phosphatidylcholine Transfer Protein

SummaryBleeding and thrombotic disorders are major complications affecting patients with chronic kidney disease (CKD). Exposure of circulating platelets to uraemic toxins and contact with artificial surfaces during dialysis induce platelet abnormalities and alter the platelet proteome. We hypothesised that these changes may be subsequent to changes in the composition and/or regulation of the platelet transcriptome. In this study, we investigated the circulating platelets of 10 CKD patients (i.e. five chronic haemodialysis patients and five stage 4 CKD uraemic patients) and five age- and sex-matched healthy subjects. We observed an alteration of the platelet messenger RNA (mRNA) and microRNA transcriptome in CKD patients. Impaired in uraemic platelets, the levels of some mRNAs and of most microRNAs appeared to be corrected by dialysis, which is consistent with a beneficial effect of dialysis and a mRNA regulatory role of platelet microRNAs. Reduced in platelets of uraemic patients, phosphatidylcholine transfer protein (PCTP) and WD repeat-containing protein 1 (WDR1) were found to be regulated by microRNAs, the latter of which involving hsa-miR-19b, a microRNA increased in platelets of uraemic patients and involved in platelet reactivity. These results suggest that an alteration of microRNA-based mRNA regulatory mechanisms may underlie the platelet response to uremia and entail the development of platelet-related complications in CKD.

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