Determinants of impaired renal and vascular function are associated with elevated levels of procoagulant factors in the general population

Dekkers, Ilona A.; Mutsert, Renée de; Vries, Aiko P. J. de; Rosendaal, Frits R.; Cannegieter, Suzanne C.; Jukema, J. Wouter; Cessie, Saskia le; Rabelink, Ton J.; Lamb, Hildo J.; Lijfering, Willem M.

doi:10.1111/jth.13935

Cited by 22 publications

(15 citation statements)

References 33 publications

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“…Our findings suggest that CKD‐induced activation of inflammation and procoagulation are in the causal pathway between eGFR and VTE. We confirmed prior findings that the studied biomarkers D‐dimer FVIII and CRP are more adverse with worsening kidney function (confirming our rationale for choosing them for this study). We also confirmed that D‐dimer , FVIII and CRP were strongly associated with VTE.…”

Section: Discussionsupporting

confidence: 89%

Mechanisms and mitigating factors for venous thromboembolism in chronic kidney disease: the REGARDS study

Cheung

Zakai

Callas

et al. 2018

Journal of Thrombosis and Haemostasis

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Background Chronic kidney disease (CKD) is associated with venous thromboembolism (VTE) risk via unknown mechanisms. Whether factors associated with reduced VTE risk in the general population might also be associated with reduced VTE risk in CKD patients is unknown. Objectives To determine whether thrombosis biomarkers attenuate VTE risk, and whether factors associated with reduced VTE risk are similarly effective in CKD patients. Methods Baseline biomarkers were measured in a cohort (294 VTE cases; 939 non-cases) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a nationwide prospective cohort study of 30 239 persons aged ≥45 years with 4.3 years of follow-up. The hazard ratio (HR) of VTE per 10 mL min 1.73 m decrease in estimated glomerular filtration rate (eGFR), and the percentage attenuation of this HR by each biomarker, were calculated. Associations of protective factors (physical activity, lower body mass index [BMI], and aspirin, warfarin and statin use) with VTE were estimated in those with and without CKD. Results The HR for VTE with lower eGFR was 1.13 (95% confidence interval [CI] 1.02-1.25), and VTE risk was attenuated by 23% (95% CI 5-100) by D-dimer, by 100% (95% CI 50-100) by factor VIII, and by 15% (95% CI 2-84) by C-reactive protein. Normal BMI was associated with lower VTE risk in those without CKD (HR 0.47, 95% CI 0.32-0.70), but not in those with CKD (HR 1.07, 95% CI 0.51-2.22). Statin use, physical activity and warfarin use were associated with lower VTE risk in both groups. Conclusions Procoagulant and inflammatory biomarkers mediated the association of eGFR with VTE. Higher physical activity, statin use and warfarin use mitigated VTE risk in those with CKD and those without CKD, but normal BMI did not mitigate VTE risk in CKD patients.

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Section: Discussionsupporting

confidence: 89%

Mechanisms and mitigating factors for venous thromboembolism in chronic kidney disease: the REGARDS study

Cheung

Zakai

Callas

et al. 2018

Journal of Thrombosis and Haemostasis

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“…Although this large population study provides necessary CMR-PWV normal and reference values, there are also some limitations to consider. Because there was a oversampling of obese participants in the NEO study, adjustments were performed by weighting individuals towards the BMI distribution of participants in the Leiderdorp subpopulation [ 31 ]. As a result, the normal and reference values do apply to the general population between 45 and 65 years.…”

Section: Discussionmentioning

confidence: 99%

Normal and reference values for cardiovascular magnetic resonance-based pulse wave velocity in the middle-aged general population

Hout

Dekkers

Westenberg

et al. 2021

Journal of Cardiovascular Magnetic Resonance

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Background Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values for cardiovascular magnetic resonance imaging (CMR) based PWV is limiting clinical implementation. The aim of this study was to determine normal and reference values for CMR assessed PWV in the general population. Methods From the 2,484 participants of the Netherlands Epidemiology of Obesity (NEO) study that have available CMR-PWV data, 1,394 participants free from cardiovasculard disease, smokers or treatment for diabetes, hypertension or dyslipidaemia were selected (45–65 years, 51% female). Participants were divided into sex, age and blood pressure (BP) subgroups. Normal values were specified for participants with a BP < 130/80 mmHg and reference values for elevated BP subgroups (≥ 130/80 and < 140/90 mmHg; and ≥ 140/90 mmHg). Differences between groups were tested with independent samples t-test or ANOVA. Due to an oversampling of obese individuals in this study, PWV values are based on a weighted analysis making them representative of the general population. Results Normal mean PWV was 6.0 m/s [95% CI 5.8–6.1]. PWV increased with advancing age and BP categories (both p < 0.001). There was no difference between sex in normal PWV, however in the BP > 140/90 mmHg women had a higher PWV (p = 0.005). The interpercentile ranges were smaller for participants < 55 years old compared to participants ≥ 55 years, indicating an increasing variability of PWV with age. PWV upper limits were particularly elevated in participants ≥ 55 years old in the high blood pressure subgroups. Conclusion This study provides normal and reference values for CMR-assessed PWV per sex, age and blood pressure category in the general population.

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“…Nevertheless, thrombocytopenia, prolonged prothrombin time and higher D-dimer levels have also been observed and associated with death in COVID-19 patients ( Liao et al, 2020 ). Notably, increased coagulation factors are correlated with decreased renal function in subjects without cardiovascular disease or chronic kidney disease (CKD; Dekkers et al, 2018 ).…”

Section: Possible Mechanisms Involved In Kidney Injury In Covid-19 Patientsmentioning

confidence: 99%

“…Notably, increased coagulation factors are correlated with decreased renal function in subjects without cardiovascular disease or chronic kidney disease (CKD; Dekkers et al, 2018).…”

Section: Sars-cov-2 Indirect Effects On Kidneys: How the Inflammatory Coagulation And Respiratory Symptoms Can Lead To Kidney Injurymentioning

confidence: 99%

Angiotensin-Converting Enzyme 2 in the Pathogenesis of Renal Abnormalities Observed in COVID-19 Patients

et al. 2021

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Coronavirus disease 2019 (COVID-19) was first reported in late December 2019 in Wuhan, China. The etiological agent of this disease is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the high transmissibility of the virus led to its rapid global spread and a major pandemic (ongoing at the time of writing this review). The clinical manifestations of COVID-19 can vary widely from non-evident or minor symptoms to severe acute respiratory syndrome and multi-organ damage, causing death. Acute kidney injury (AKI) has been recognized as a common complication of COVID-19 and in many cases, kidney replacement therapy (KRT) is required. The presence of kidney abnormalities on hospital admission and the development of AKI are related to a more severe presentation of COVID-19 with higher mortality rate. The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, angiotensin (Ang)-converting enzyme 2 (ACE2), which is widely expressed in human organs and is especially abundant in the kidneys. A debate on the role of ACE2 in the infectivity and pathogenesis of COVID-19 has emerged: Does the high expression of ACE2 promotes higher infectivity and more severe clinical manifestations or does the interaction of SARS-CoV-2 with ACE2 reduce the bioavailability of the enzyme, depleting its biological activity, which is closely related to two important physiological systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), thereby further contributing to pathogenesis. In this review, we discuss the dual role of ACE2 in the infectivity and pathogenesis of COVID-19, highlighting the effects of COVID-19-induced ACE2 depletion in the renal physiology and how it may lead to kidney injury. The ACE2 downstream regulation of KKS, that usually receives less attention, is discussed. Also, a detailed discussion on how the triad of symptoms (respiratory, inflammatory, and coagulation symptoms) of COVID-19 can indirectly promote renal injury is primary aborded.

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Determinants of impaired renal and vascular function are associated with elevated levels of procoagulant factors in the general population

Cited by 22 publications

References 33 publications

Mechanisms and mitigating factors for venous thromboembolism in chronic kidney disease: the REGARDS study

Mechanisms and mitigating factors for venous thromboembolism in chronic kidney disease: the REGARDS study

Normal and reference values for cardiovascular magnetic resonance-based pulse wave velocity in the middle-aged general population

Angiotensin-Converting Enzyme 2 in the Pathogenesis of Renal Abnormalities Observed in COVID-19 Patients

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