scholarly journals Inhibition of microbiota-dependent TMAO production attenuates chronic kidney disease in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenchao Zhang ◽  
Aika Miikeda ◽  
Jonathan Zuckerman ◽  
Xun Jia ◽  
Sarada Charugundla ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Surrogate Marker ◽  
Heart Weight ◽  
Increased Risk ◽  
Apoe Ko Mice ◽  
Novel Strategy ◽  
Kidney Impairment ◽  
Circulating Levels

AbstractPatients with chronic kidney disease (CKD) have elevated circulating levels of trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes and associated with cardiovascular diseases. High circulating levels of TMAO and its dietary precursor, choline, predict increased risk for development of CKD in apparently healthy subjects, and studies in mice fed TMAO or choline suggest that TMAO can contribute to kidney impairment and renal fibrosis. Here we examined the interactions between TMAO, kidney disease, and cardiovascular disease in mouse models. We observed that while female hyperlipidemic apoE KO mice fed a 0.2% adenine diet for 14 weeks developed CKD with elevated plasma levels of TMAO, provision of a non-lethal inhibitor of gut microbial trimethylamine (TMA) production, iodomethylcholine (IMC), significantly reduced multiple markers of renal injury (plasma creatinine, cystatin C, FGF23, and TMAO), reduced histopathologic evidence of fibrosis, and markedly attenuated development of microalbuminuria. In addition, while the adenine-induced CKD model significantly increased heart weight, a surrogate marker for myocardial hypertrophy, this was largely prevented by IMC supplementation. Surprisingly, adenine feeding did not increase atherosclerosis and significantly decreased the expression of inflammatory genes in the aorta compared to the control groups, effects unrelated to TMAO levels. Our data demonstrate that inhibition of TMAO production attenuated CKD development and cardiac hypertrophy in mice, suggesting that TMAO reduction may be a novel strategy in treating CKD and its cardiovascular disease complications.

scholarly journals Risk for recurrent cardiovascular disease events among patients with diabetes and chronic kidney disease

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Demetria Hubbard ◽  
Lisandro D. Colantonio ◽  
Robert S. Rosenson ◽  
Todd M. Brown ◽  
Elizabeth A. Jackson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Health Insurance ◽  
High Risk ◽  
Kidney Disease ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Very High

Abstract Background Adults who have experienced multiple cardiovascular disease (CVD) events have a very high risk for additional events. Diabetes and chronic kidney disease (CKD) are each associated with an increased risk for recurrent CVD events following a myocardial infarction (MI). Methods We compared the risk for recurrent CVD events among US adults with health insurance who were hospitalized for an MI between 2014 and 2017 and had (1) CVD prior to their MI but were free from diabetes or CKD (prior CVD), and those without CVD prior to their MI who had (2) diabetes only, (3) CKD only and (4) both diabetes and CKD. We followed patients from hospital discharge through December 31, 2018 for recurrent CVD events including coronary, stroke, and peripheral artery events. Results Among 162,730 patients, 55.2% had prior CVD, and 28.3%, 8.3%, and 8.2% had diabetes only, CKD only, and both diabetes and CKD, respectively. The rate for recurrent CVD events per 1000 person-years was 135 among patients with prior CVD and 110, 124 and 171 among those with diabetes only, CKD only and both diabetes and CKD, respectively. Compared to patients with prior CVD, the multivariable-adjusted hazard ratio for recurrent CVD events was 0.92 (95%CI 0.90–0.95), 0.89 (95%CI: 0.85–0.93), and 1.18 (95%CI: 1.14–1.22) among those with diabetes only, CKD only, and both diabetes and CKD, respectively. Conclusion Following MI, adults with both diabetes and CKD had a higher risk for recurrent CVD events compared to those with prior CVD without diabetes or CKD.

scholarly journals REPRINT Detection of Chronic Kidney Disease in Patients With or at Increased Risk of Cardiovascular Disease

Hypertension ◽  
2006 ◽  
Vol 48 (4) ◽  
pp. 751-755 ◽  
Author(s):  
Frank C. Brosius ◽  
Thomas H. Hostetter ◽  
Ellie Kelepouris ◽  
Mark M. Mitsnefes ◽  
Sharon M. Moe ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Increased Risk

scholarly journals Low statin use in nondialysis-dependent chronic kidney disease in the absence of clinical atherosclerotic cardiovascular disease or diabetes

2019 ◽  
Vol 12 (4) ◽  
pp. 530-537
Author(s):  
Talar W Markossian ◽  
Holly J Kramer ◽  
Nicholas J Burge ◽  
Ivan V Pacold ◽  
David J Leehey ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Risk Equation ◽  
Diabetes Status ◽  
Increased Risk ◽  
Ascvd Risk ◽  
Risk Equivalent ◽  
Statin Use

Abstract Background Both reduced glomerular filtration rate and increased urine albumin excretion, markers of chronic kidney disease (CKD), are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). However, CKD is not recognized as an ASCVD risk equivalent by most lipid guidelines. Statin medications, especially when combined with ezetimibe, significantly reduce ASCVD risk in patients with nondialysis-dependent CKD. Unless physicians recognize the heightened ASCVD risk in this population, statins may not be prescribed in the absence of clinical cardiovascular disease or diabetes, a recognized ASCVD risk equivalent. We examined statin use in adults with nondialysis-dependent CKD and examined whether the use differed in the presence of clinical ASCVD and diabetes. Methods This study ascertained statin use from pharmacy dispensing records during fiscal years 2012 and 2013 from the US Department of Veterans Affairs Healthcare System. The study included 581 344 veterans aged ≥50 years with nondialysis-dependent CKD Stages 3–5 with no history of kidney transplantation or dialysis. The 10-year predicted ASCVD risk was calculated with the pooled risk equation. Results Of veterans with CKD, 62.1% used statins in 2012 and 55.4% used statins continuously over 2 years (2012–13). Statin use in 2012 was 76.2 and 75.5% among veterans with CKD and ASCVD or diabetes, respectively, but in the absence of ASCVD, diabetes or a diagnosis of hyperlipidemia, statin use was 21.8% (P < 0.001). The 10-year predicted ASCVD risk was ≥7.5% in 95.1% of veterans with CKD, regardless of diabetes status. Conclusions Statin use is low in veterans with nondialysis-dependent CKD in the absence of ASCVD or diabetes despite high-predicted ASCVD risk. Future studies should examine other populations.

High circulating levels of large splice variants of tenascin-C is associated with mortality and cardiovascular disease in chronic kidney disease patients

2011 ◽  
Vol 215 (1) ◽  
pp. 116-124 ◽  
Author(s):  
Sophie Liabeuf ◽  
Daniela V. Barreto ◽  
Axel Kretschmer ◽  
Fellype C. Barreto ◽  
Cédric Renard ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Splice Variants ◽  
Tenascin C ◽  
Circulating Levels

scholarly journals Cardiovascular Risk Factors and Chronic Kidney Disease—FGF23: A Key Molecule in the Cardiovascular Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Rika Jimbo ◽  
Tatsuo Shimosawa
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Cardiovascular Risks ◽  
Mineral And Bone Disorder ◽  
Promising Target ◽  
Increased Risk

Patients with chronic kidney disease (CKD) are at increased risk of mortality, mainly from cardiovascular disease. Moreover, abnormal mineral and bone metabolism, the so-called CKD-mineral and bone disorder (MBD), occurs from early stages of CKD. This CKD-MBD presents a strong cardiovascular risk for CKD patients. Discovery of fibroblast growth factor 23 (FGF23) has altered our understanding of CKD-MBD and has revealed more complex cross-talk and endocrine feedback loops between the kidney, parathyroid gland, intestines, and bone. During the past decade, reports of clinical studies have described the association between FGF23 and cardiovascular risks, left ventricular hypertrophy, and vascular calcification. Recent translational reports have described the existence of FGF23-Klotho axis in the vasculature and the causative effect of FGF23 on cardiovascular disease. These findings suggest FGF23 as a promising target for novel therapeutic approaches to improve clinical outcomes of CKD patients.

scholarly journals Providing Care for Transgender Persons With Kidney Disease: A Narrative Review

2021 ◽  
Vol 8 ◽  
pp. 205435812098537
Author(s):  
David Collister ◽  
Nathalie Saad ◽  
Emily Christie ◽  
Sofia Ahmed
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Hormone Therapy ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Transgender Persons ◽  
Increased Risk ◽  
The Impact

Purpose of review: Nephrologists are increasingly providing care to transgender individuals with chronic kidney disease (CKD). However, they may lack familiarity with this patient population that faces unique challenges. The purpose of this review is to discuss the care of transgender persons and what nephrologists should be aware of when providing care to their transgender patients. Sources of information: Original research articles were identified from MEDLINE and Google Scholar using the search terms “transgender,” “gender,” “sex,” “chronic kidney disease,” “end stage kidney disease,” “dialysis,” “transplant,” and “nephrology.” Methods: A focused review and critical appraisal of existing literature regarding the provision of care to transgender men and women with CKD including dialysis and transplant to identify specific issues related to gender-affirming therapy and chronic disease management in transgender persons. Key findings: Transgender persons are at an increased risk of adverse outcomes compared with the cisgender population including mental health, cardiovascular disease, malignancy, sexually transmitted infections, and mortality. Individuals with CKD have a degree of hypogonadotropic hypogonadism and decreased levels of endogenous sex hormones; therefore, transgender persons with CKD may require reduced exogenous sex hormone dosing. Exogenous estradiol therapy increases the risk of venous thromboembolism and cardiovascular disease which may be further increased in CKD. Exogenous testosterone therapy increases the risk of polycythemia which should be closely monitored. The impact of gender-affirming hormone therapy on glomerular filtration rate (GFR) trajectory in CKD is unclear. Gender-affirming hormone therapy with testosterone, estradiol, and anti-androgen therapies changes body composition and lean body mass which influences creatinine generation and the performance for estimated glomerular filtration rate (eGFR) equations in transgender persons. Confirmation of eGFR with measured GFR is reasonable if an accurate knowledge of GFR is needed for clinical decision-making. Limitations: There are limited studies regarding the intersection of transgender persons and kidney disease and those that exist are mostly case reports. Randomized controlled trials and observational studies in nephrology do not routinely differentiate between cisgender and transgender participants. Implications: This review highlights important considerations for providing care to transgender persons with kidney disease. Additional research is needed to evaluate the performance of eGFR equations in transgender persons, the effects of gender-affirming hormone therapy, and the impact of being transgender on outcomes in persons with kidney disease.

scholarly journals The association between atrial fibrillation and in-hospital outcomes in chronic kidney disease patients with acute coronary syndrome: findings from the improving care for cardiovascular disease in China-acute coronary syndrome (CCC-ACS) project

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lijiao Yang ◽  
Nan Ye ◽  
Guoqin Wang ◽  
Weijing Bian ◽  
Fengbo Xu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
Kidney Disease ◽  
Hospital Mortality ◽  
Major Adverse Cardiovascular Events ◽  
Coronary Syndrome ◽  
Risk Of Mortality ◽  
Increased Risk

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in patients with chronic kidney disease (CKD) and acute coronary syndrome (ACS). This study aimed to explore the frequency and impact of AF on clinical outcomes in CKD patients with ACS. Methods CKD inpatients with ACS between November 2014 and December 2018 were included based on the improving care for cardiovascular disease in China-ACS (CCC-ACS) project. Included patients were divided into an AF group and a non-AF group according to the discharge diagnosis. Multivariable logistic regression was used to adjust for potential confounders. Results A total of 16,533 CKD patients with ACS were included. A total of 1418 (8.6%) patients had clinically recognized AF during hospitalization, 654 of whom had an eGFR of 45 to < 60 ml/min/1.73 m2, and 764 had an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2. Compared with the non-AF group, the AF group had a higher risk of in-hospital mortality [OR 1.250; 95% CI (1.001–1.560), P = 0.049] and major adverse cardiovascular events (MACEs) [OR 1.361; 95% CI (1.197–1.547), P < 0.001]. We also found that compared with patients with eGFR 45 to < 60 ml/min/1.73 m2, patients with eGFR < 45 ml/min/1.73 m2 had a 1.512-fold increased risk of mortality and a 1.435-fold increased risk of MACEs. Conclusions AF was a risk factor affecting the short-term prognosis of ACS patients in the CKD population. Furthermore, the lower the eGFR, the higher the risk of in-hospital mortality and MACEs in CKD patients with ACS. Trial registry: Clinicaltrial.gov, NCT02306616. Registered 29 November 2014, https://clinicaltrials.gov/ct2/show/NCT02306616?term=NCT02306616&draw=2&rank=1

scholarly journals Cardiac status in patients of chronic kidney disease: an assessment by non-invasive tools

2016 ◽  
Vol 15 (2) ◽  
pp. 207-215
Author(s):  
Kiran Kumar Singal ◽  
Neerja Singal ◽  
Parveen Gupta ◽  
Jagdish Chander ◽  
Pankaj Relan
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Left Ventricular Mass ◽  
Left Ventricular ◽  
Treatment Schedule ◽  
Ventricular Mass ◽  
Increased Risk ◽  
History Of ◽  
Cardiac Status

Background: Chronic Renal Insufficiency is a major public health problem. Cardiovascular Disease is the leading cause of morbidity and mortality in patients at every stage of Chronic Kidney Disease. There is a 10-200 fold increased risk of cardiovascular disease in those with Chronic Kidney Disease compared to the age and sex matched with general population, depending on the stage of Chronic Kidney Disease. Objective: The objective of the study was to see correlation, if any, of cardiac status and stage of kidney disease. Materials and methods: The study was conducted at M. M. Institute of Medical Sciences and Research, Mullana, Ambala. Thirty patients of Chronic Kidney Disease were included in the study. Chronic Kidney Disease is defined as kidney damage lasting for more than 3 months characterised by structural or functional abnormalities of the kidney, with or without decreased Glomerular Filtration Rate (GFR), according to the K/DOQI Guidelines. Inclusion criteria were based on symptomatology and clinical history of features suggestive of Chronic Kidney Disease. Symptoms, Signs and history of the patients were used to filter out patients who did not fit in the criteria and selected patients on the basis of criteria were further evaluated and investigated. All patients were subjected to detailed history and clinical examination. Patients with age <20 years, with history of Diabetes Mellitus, Dyslipidemia, Intrinsic Diseases of Ventricles, Congenital Heart Disease and chronic smokers were excluded from the study. A standard 12 lead ECG was done in all cases. Echocardiography was done in ECHO lab of Cardiology unit in MMIMSR. Echocardiographic assessment was done by using Model vivid Colour Doppler Echocardiography machine of GE make. Apical four chamber view was employed to obtain the measurements of Left ventricular volume in diastole and systole, Ejection fraction; Left Ventricular Indices were assessed and then were used to calculate Left Ventricular Mass by using the cube formula proposed by Devereux. Patients included in the study were treated as per the standard treatment schedule. The data obtained was analysed with appropriate statistical analysis tools at the end of the study and conclusive evidence was derived. Results: In the present study the mean Left Ventricular Mass was 249.76 ± 69.35 gms with 73% study cases having Left Ventricular Mass more than the reference range, also Left Ventricular Mass showed a progressive rise with increase in S. Creatinine levels. In the present study, Left Ventricular dysfunction was seen in nearly half of the cases while approximately one-fourth cases (23%) also had Systolic Dysfunction. Pericardial Effusion was also observed in 10 % the study cases in the present study.Conclusion: Cardiac functions particularly Left Ventricular parameters. Left Ventricular free wall thickness and Left Ventricular Mass being common abnormality in CKD patients.Bangladesh Journal of Medical Science Vol.15(2) 2016 p.207-215

Abstract 557: Human S100/calgranulin Accelerates Ectopic Cardiac Calcification and Promotes Cardiac Hypertrophy in Transgenic Mice with Chronic Kidney Disease in a RAGE Dependent Manner

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Marion Hofmann Bowman ◽  
Ling Yan ◽  
Liby Mathew ◽  
Bijoy Chellan ◽  
Brandon Gardner ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Elevated Serum ◽  
Regulatory Elements ◽  
Heart Weight ◽  
Dependent Manner ◽  
Alizarin Red

Purpose Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease. Elevated serum S100A12 predicts cardiovascular mortality in patients with end stage renal disease. We test the hypothesis that human S100/calgranulin transgenic mice exposed to the metabolic changes of CKD would develop accelerated cardiovascular disease. Methods A novel humanized mouse with transgenic expression of human S100/calgranulin (hBAC-S100) was generated by expression of a bacterial artificial chromosome of the human S100/calgranulin gene cluster containing genes and regulatory elements for S1008/9 and S100A12 (60kb) in C57BL6/J mice. The hBAC-S100 mice were crossed with the RAGE KO mice (same C57BL6/J strain, gift from Ann Marie Schmidt, NYU) and F4 animals were used for the experiment. CKD was induced in hBAC-S100 and wild type (WT) littermate mice with intact or lacking RAGE signaling by surgical ligation of the ureters. The heart and aorta were analyzed after 10 weeks of elevated blood urea nitrogen. Results hBAC-S100 mice express human S100A12 in circulating myeloid cells and S100A12 was present in the serum of hBAC-S100 mice (25 ng/ml serum), but was not detected in WT mice. Importantly, serum hS100A12 was increased in hBAC-S100 mice with CKD compared to sham operated hBAC-S100 mice (42±17 ng/ml and 25±7 ng/ml, p=0.04). Moreover, hBAC-S100 mice with CKD exhibited ectopic cardiac calcification in fibroblast-rich annulus of the mitral and aortic valves upon Alizarin Red staining. In vivo ECHO showed abnormal mitral valve doppler flow with reduced ratio of early (E) to atrial (A) filling in hBAC-S100 mice with CKD compared to WT-CKD mice (1.17 ±0.1 vs 1.35 ±0.1, p=0.003), indicating diastolic dysfunction. Notably, hBAC-S100 mice with CKD develop cardiac hypertrophy as evidenced by increased heart weight/ body weight ratio and elevated gene expression of hypertrophic and fibrotic markers, such as ANP, β-MHC, TGF-β, CTGF, and Col 1a1. This phenotype was not observed in hBAC-S100 mice lacking RAGE, despite exposure to the same degree of CKD. Conclusion Circulating myeloid derived human S100/calgranulin is associated with the development of ectopic cardiac calcification and cardiac hypertrophy in chronic kidney disease in a RAGE dependent manner.

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