scholarly journals Machine learning analysis of serum biomarkers for cardiovascular risk assessment in chronic kidney disease

2019 ◽  
Author(s):  
Carles Forné ◽  
Serafi Cambray ◽  
Marcelino Bermudez-Lopez ◽  
Elvira Fernandez ◽  
Milica Bozic ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Kidney Disease ◽  
Cardiovascular Death ◽  
Lipid Lowering ◽  
Cardiovascular Risk Prediction ◽  
Competing Events ◽  
Endothelial Growth Factor

Abstract Background Chronic kidney disease (CKD) patients show an increased burden of atherosclerosis and high risk of cardiovascular events (CVEs). There are several biomarkers described as being associated with CVEs, but their combined effectiveness in cardiovascular risk stratification in CKD has not been tested. The objective of this work is to analyse the combined ability of 19 biomarkers associated with atheromatous disease in predicting CVEs after 4 years of follow-up in a subcohort of the NEFRONA study in individuals with different stages of CKD without previous CVEs. Methods Nineteen putative biomarkers were quantified in 1366 patients (73 CVEs) and their ability to predict CVEs was ranked by random survival forest (RSF) analysis. The factors associated with CVEs were tested in Fine and Gray (FG) regression models, with non-cardiovascular death and kidney transplant as competing events. Results RSF analysis detected several biomarkers as relevant for predicting CVEs. Inclusion of those biomarkers in an FG model showed that high levels of osteopontin, osteoprotegerin, matrix metalloproteinase-9 and vascular endothelial growth factor increased the risk for CVEs, but only marginally improved the discrimination obtained with classical clinical parameters: concordance index 0.744 (95% confidence interval 0.609–0.878) versus 0.723 (0.592–0.854), respectively. However, in individuals with diabetes treated with antihypertensives and lipid-lowering drugs, the determination of these biomarkers could help to improve cardiovascular risk estimates. Conclusions We conclude that the determination of four biomarkers in the serum of CKD patients could improve cardiovascular risk prediction in high-risk individuals.

MO817ALDOSTERONE ANTAGONISTS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE REQUIRING DIALYSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Hiroki Nihiwaki ◽  
Erika Ota ◽  
William Levack ◽  
Hisashi Noma
Keyword(s):  
Chronic Kidney Disease ◽  
High Risk ◽  
Kidney Disease ◽  
Standard Care ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Aldosterone Antagonists ◽  
Mortality And Morbidity ◽  
Risk Of Death ◽  
Increased Risk

Abstract Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.

scholarly journals MO159CHA2DS2-VASC SCORE AS A PREDICTOR OF CARDIOVASCULAR MORTALITY IN CHRONIC KIDNEY DISEASE PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Nina Vodošek Hojs ◽  
Robert Ekart ◽  
Sebastjan Bevc ◽  
Nejc Piko ◽  
Radovan Hojs
Keyword(s):  
Chronic Kidney Disease ◽  
Regression Analysis ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Cardiovascular Mortality ◽  
Cox Regression ◽  
High Sensitivity ◽  
Cardiovascular Death ◽  
Cox Regression Analysis

Abstract Background and Aims Cardiovascular mortality is high in chronic kidney disease (CKD) patients. Recognizing patients with higher cardiovascular risk might help in their treatment. CHA2DS2-VASc score was originally used to predict cerebral infarction in patients with atrial fibrillation (AF). However, it is also useful in predicting outcome in different cardiovascular conditions, independent of the presence of AF. Therefore, the aim of our research was to assess the role of CHA2DS2-VASc score in cardiovascular mortality in CKD patients. Method Eighty-seven non-dialysis CKD patients from our outpatient clinic were included. At the time of inclusion, medical history data and standard blood results were collected and CHA2DS2-VASc score was calculated. Patients were followed for assigned time or until their death. Mean follow-up time was 1696.45±564.60 days. Results Descriptive statistics of our patients are presented in table 1. During follow-up 11 patients suffered from cardiovascular death. Univariate Cox regression analysis showed that CHA2DS2-VASc score is a significant predictor of cardiovascular mortality (HR: 2.19, CI: 1.42-3.37, p=0.001). In multivariate Cox regression analysis in which CHA2DS2-VASc score, serum creatinine, urinary albumin/creatinine, haemoglobin, high sensitivity CRP and intact PTH were included, CHA2DS2-VASc score was an independent predictor of cardiovascular mortality (HR: 2.04, CI: 1.20-3.45, p=0.008) (table 2). Conclusion CHA2DS2-VASc score is a simple and quick way to identify cardiovascular risk in CKD patients.

P5526Vascular endothelial growth factor-D and mortality in suspected or known coronary heart disease patients with chronic kidney disease: a subanalysis of the ANOX study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Wada ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
T Shinozaki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Coronary Angiography ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Endothelial Growth Factor

Abstract Background Chronic kidney disease (CKD) is an independent risk factor for the development and progression of coronary heart disease (CHD). Vascular endothelial growth factor-D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors through binding to its specific receptors, VEGFR-3 (Flt-4) and VEGFR-2 (KDR/Flk-1). VEGF-D signaling via VEGFR-3 plays an important role in lipoprotein metabolisms which may contribute to CHD. VEGF-D signaling has been used as a therapeutic target of human diseases such as lymphangioleiomyomatosis and refractory angina. Furthermore, in clinical settings, the VEGF-D level is already established as a diagnostic biomarker for lymphangioleiomyomatosis. However, the prognostic value of VEGF-D in suspected or known CHD patients with CKD is unknown. Methods Serum VEGF-D levels were measured in 999 suspected or known CHD patients with CKD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 154 patients died from any cause, 61 died from cardiovascular disease, and 96 developed MACE. After adjustment for established risk factors, VEGF-D levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.41; 95% confidence interval [CI], 1.27–1.56), cardiovascular death (HR, 1.48; 95% CI, 1.28–1.71), and MACE (HR, 1.34; 95% CI, 1.18–1.53). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-D levels further improved the prediction of all-cause death (continuous net reclassification improvement [NRI], 0.272; 95% CI, 0.100–0.445; P=0.002; integrated discrimination improvement [IDI], 0.015; 95% CI, 0.003–0.027; P=0.013), but not that of cardiovascular death (NRI, 0.230; 95% CI, −0.029 to 0.488; P=0.082; IDI, 0.012; 95% CI, −0.007 to 0.031; P=0.207) or MACE (NRI, 0.102; 95% CI, −0.106 to 0.310; P=0.337; IDI, 0.005; 95% CI, −0.005 to 0.015; P=0.337). Conclusions In suspected or known CHD patients with CKD undergoing elective coronary angiography, elevated VEGF-D levels may predict all-cause mortality independent of established risk factors and cardiovascular biomarkers. Acknowledgement/Funding The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization

scholarly journals Cardiovascular risk prediction in chronic kidney disease patients

2017 ◽  
Vol 37 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Santiago Cedeño Mora ◽  
Marian Goicoechea ◽  
Esther Torres ◽  
Úrsula Verdalles ◽  
Ana Pérez de José ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Risk Prediction ◽  
Cardiovascular Risk Prediction

scholarly journals Urinary Osteopontin Predicts Incident Chronic Kidney Disease, while Plasma Osteopontin Predicts Cardiovascular Death in Elderly Men

2017 ◽  
Vol 7 (3) ◽  
pp. 245-254 ◽  
Author(s):  
Tobias Feldreich ◽  
Axel C. Carlsson ◽  
Johanna Helmersson-Karlqvist ◽  
Ulf Risérus ◽  
Anders Larsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Cardiovascular Risk Factors ◽  
Cardiovascular Death ◽  
Matricellular Protein ◽  
Elderly Men ◽  
Cross Sectional ◽  
Incident Chronic Kidney Disease

Background and Objectives: The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied. Design, Setting, Participants, and Measurements: A community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM]; n = 741; mean age: 77 years) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up. Results: There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman ρ = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/creatinine ratio, and the inflammatory markers interleukin 6 and high-sensitivity C-reactive protein (odds ratio for 1 standard deviation [SD] of urinary osteopontin, 1.42, 95% CI 1.00-2.02, p = 0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI 1.14-1.58, p < 0.001, and 1.00, 95% CI 0.79-1.26, p = 0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p < 0.002). Conclusions: Higher urinary osteopontin specifically predicts incident chronic kidney disease, while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remain to be established.

scholarly journals Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

2020 ◽  
Vol 13 (6) ◽  
pp. 1017-1024 ◽  
Author(s):  
Serafi Cambray ◽  
Marcelino Bermudez-Lopez ◽  
Milica Bozic ◽  
Jose M Valdivielso ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Rare Allele ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Klotho Gene

Abstract Background Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with non-cardiovascular death in CKD populations are lacking. Methods The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n = 2185 CKD patients). Results After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG + rs2283368 CC/CT + rs2320762 GG). Among the patients with the three SNPs genotyped (n = 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA + rs2283368 TT + rs2320762 GT/TT). All the other combinations [n = 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher {hazard ratio [HR] 3.28 [confidence interval (CI) 1.51–7.12]} and lower [HR 6 × 10−6 (95% CI 3.3 × 10−7–1.1 × 10−5)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Conclusions Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD.

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