| 1. |
- Erlandsson, Helen, et al.
(author)
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Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation
- 2022
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 291:6, s. 813-823
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Journal article (peer-reviewed)abstract
- Background Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. Methods In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow-up time was 6.4 years (interquartile range 3.7-9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow-up, that is, living donor KT, deceased donor KT, or dialysis. Results Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12-9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10-year mortality in the dialysis group was 33.6 (95% CI, 10.0-113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. Conclusion Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT.
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| 2. |
- Golembiewska, Edyta, et al.
(author)
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Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5
- 2020
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In: BMC Nephrology. - Stockholm : Karolinska Institutet, Dept of Clinical Science, Intervention and Technology. - 1471-2369.
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Journal article (peer-reviewed)abstract
- Background: Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30– 70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5. Methods: Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography. Results: Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman’s rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC. Conclusions: High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.
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| 3. |
- Heil, Jan, et al.
(author)
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Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection-A DRAGON collaborative analysis of 306 patients
- 2022
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In: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 24:3, s. 413-421
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Journal article (peer-reviewed)abstract
- Background: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. Methods: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. Results: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p < 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR >2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. Conclusion: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.
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| 4. |
- Laucyte-Cibulskiene, Agne, et al.
(author)
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Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease : focus on sex-specific associations with vascular outcomes and all-cause mortality
- 2021
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In: Biology of Sex Differences. - : Springer Science and Business Media LLC. - 2042-6410. ; 12:1
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Journal article (peer-reviewed)abstract
- Background: Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods: ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results: Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02). Conclusions: In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.
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| 5. |
- Niklasson, Erik, et al.
(author)
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Assessment of anterior thigh muscle size and fat infiltration using single-slice CT imaging versus automated MRI analysis in adults
- 2022
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In: British Journal of Radiology. - London, United Kingdom : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 95:1133
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Journal article (peer-reviewed)abstract
- Objectives: We examined the longitudinal and cross- sectional relationship between automated MRI-analysis and single-slice axial CT imaging for determining muscle size and muscle fat infiltration (MFI) of the anterior thigh.Methods: Twenty-two patients completing sex-hormone treatment expected to result in muscle hypertrophy (n = 12) and atrophy (n = 10) underwent MRI scans using 2-point Dixon fat/water-separated sequences and CT scans using a system operating at 120 kV and a fixed flux of 100 mA. At baseline and 12 months after, auto- mated volumetric MRI analysis of the anterior thigh was performed bilaterally, and fat-free muscle volume and MFI were computed. In addition, cross-sectional area (CSA) and radiological attenuation (RA) (as a marker of fat infiltration) were calculated from single slice axial CT-images using threshold-assisted planimetry. Linear regression models were used to convert units.Results: There was a strong correlation between MRI- derived fat-free muscle volume and CT-derived CSA (R = 0.91), and between MRI-derived MFI and CT-derived RA (R = −0.81). The 95% limits of agreement were ±0.32 L for muscle volume and ±1.3% units for %MFI. The longi- tudinal change in muscle size and MFI was comparable across imaging modalities.Conclusions: Both automated MRI and single-slice CT-imaging can be used to reliably quantify anterior thigh muscle size and MFI.Advances in knowledge: This is the first study examining the intermodal agreement between automated MRI anal- ysis and CT-image assessment of muscle size and MFI in the anterior thigh muscles. Our results support that both CT- and MRI-derived measures of muscle size and MFI can be used in clinical settings.
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| 6. |
- Nyman, Ulf, et al.
(author)
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Absolute and relative GFR and contrast medium dose/GFR ratio : cornerstones when predicting the risk of acute kidney injury.
- 2024
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In: European Radiology. - 0938-7994 .- 1432-1084. ; 31:1, s. 612-621
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Journal article (peer-reviewed)abstract
- Glomerular filtration rate (GFR) is considered the best overall index of kidney function in health and disease and its use is recommended to evaluate the risk of iodine contrast medium-induced acute kidney injury (CI-AKI) either as a single parameter or as a ratio between the total contrast medium dose (gram iodine) and GFR. GFR may be expressed in absolute terms (mL/min) or adjusted/indexed to body surface area, relative GFR (mL/min/1.73 m2). Absolute and relative GFR have been used interchangeably to evaluate the risk of CI-AKI, which may be confusing and a potential source of errors. Relative GFR should be used to assess the GFR category of renal function as a sign of the degree of kidney damage and sensitivity for CI-AKI. Absolute GFR represents the excretion capacity of the individual and may be used to calculate the gram-iodine/absolute GFR ratio, an index of systemic drug exposure (amount of contrast medium in the body) that relates to toxicity. It has been found to be an independent predictor of AKI following percutaneous coronary angiography and interventions but has not yet been fully validated for computed tomography (CT). Prospective studies are warranted to evaluate the optimal gram-iodine/absolute GFR ratio to predict AKI at various stages of renal function at CT. Only GFR estimation (eGFR) equations based on standardized creatinine and/or cystatin C assays should be used. eGFRcystatin C/eGFRcreatinine ratio < 0.6 indicating selective glomerular hypofiltration syndrome may have a stronger predictive power for postcontrast AKI than creatinine-based eGFR. CLINICAL RELEVANCE STATEMENT: Once the degree of kidney damage is established by estimating relative GFR (mL/min/1.73 m2), contrast dose in relation to renal excretion capacity [gram-iodine/absolute GFR (mL/min)] may be the best index to evaluate the risk of contrast-induced kidney injury. KEY POINTS: • Relative glomerular filtration rate (GFR; mL/min/1.73 m2) should be used to assess the GFR category as a sign of the degree of kidney damage and sensitivity to contrast medium-induced acute kidney injury (CI-AKI). • Absolute GFR (mL/min) is the individual's actual excretion capacity and the contrast-dose/absolute GFR ratio is a measure of systemic exposure (amount of contrast medium in the body), relates to toxicity and should be expressed in gram-iodine/absolute GFR (mL/min). • Prospective studies are warranted to evaluate the optimal contrast medium dose/GFR ratio predicting the risk of CI-AKI at CT and intra-arterial examinations.
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| 7. |
- Parker, Louis P., et al.
(author)
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Cannulation configuration and recirculation in venovenous extracorporeal membrane oxygenation
- 2022
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- Venovenous extracorporeal membrane oxygenation is a treatment for acute respiratory distress syndrome. Femoro-atrial cannulation means blood is drained from the inferior vena cava and returned to the superior vena cava; the opposite is termed atrio-femoral. Clinical data comparing these two methods is scarce and conflicting. Using computational fluid dynamics, we aim to compare atrio-femoral and femoro-atrial cannulation to assess the impact on recirculation fraction, under ideal conditions and several clinical scenarios. Using a patient-averaged model of the venae cavae and right atrium, commercially-available cannulae were positioned in each configuration. Additionally, occlusion of the femoro-atrial drainage cannula side-holes with/without reduced inferior vena cava inflow (0-75%) and retraction of the atrio-femoral drainage cannula were modelled. Large-eddy simulations were run for 2-6L/min circuit flow, obtaining time-averaged flow data. The model showed good agreement with clinical atrio-femoral recirculation data. Under ideal conditions, atrio-femoral yielded 13.5% higher recirculation than femoro-atrial across all circuit flow rates. Atrio-femoral right atrium flow patterns resembled normal physiology with a single large vortex. Femoro-atrial cannulation resulted in multiple vortices and increased turbulent kinetic energy at > 3L/min circuit flow. Occluding femoro-atrial drainage cannula side-holes and reducing inferior vena cava inflow increased mean recirculation by 11% and 32%, respectively. Retracting the atrio-femoral drainage cannula did not affect recirculation. These results suggest that, depending on drainage issues, either atrio-femoral or femoro-atrial cannulation may be preferrable. Rather than cannula tip proximity, the supply of available venous blood at the drainage site appears to be the strongest factor affecting recirculation.
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| 8. |
- Parker, Louis P., et al.
(author)
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Computational Fluid Dynamics of the Right Atrium : A Comparison of Modeling Approaches in a Range of Flow Conditions
- 2022
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In: Journal of Engineering and Science in Medical Diagnostics and Therapy. - : ASME International. - 2572-7958 .- 2572-7966. ; 5:3
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Journal article (peer-reviewed)abstract
- The right atrium (RA) combines flows from the inferior (IVC) and superior vena cava (SVC). Here RA mixing is simulated using computational fluid dynamics, comparing four modeling approaches. A patient-averaged model (11 M cells) was created from four volunteers. We compared: (1) unsteady k–ω Reynolds-averaged Navier–Stokes (URANS) (2) implicit large eddy simulation with second-order upwind convection scheme (iLES-SOU) (3) iLES with bounded-central difference convection scheme (iLES-BCD) and (4) LES with wall-adapting local eddy-viscosity (LES-WALE). A constant inlet flow rate of 6 L/min was applied with both IVC/SVC contributions ranging from 30–70%. A higher density mesh (37 M cells) was also simulated for models 2 and 4 (equal IVC/SVC flow) to assess the accuracy of models 1–4. Results from the 11 M cell LES-WALE model showed good agreement with the 37 M cell meshes. All four 11 M cell models captured the same large-scale flow structures. There were local differences in velocity, time-averaged wall shear stress, and IVC/SVC mixing when compared to LES-WALE, particularly at high SVC flow. Energy spectra and velocity animations from the LES-WALE model suggest the presence of transitional flow. For the general flow structures, all four methods provide similar results, though local quantities can vary greatly. On coarse meshes, the convection scheme and subgrid-scale (SGS) model have a significant impact on results. For RA flows, URANS should be avoided and iLES models are sensitive to convection scheme unless used on a highly resolved grid.
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| 9. |
- Parker, Louis P., et al.
(author)
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Hemodynamic and recirculation performance of dual lumen cannulas for venovenous extracorporeal membrane oxygenation
- 2023
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Venovenous extracorporeal membrane oxygenation (ECMO) can be performed with two single lumen cannulas (SLCs) or one dual-lumen cannula (DLC) where low recirculation fraction (Rf) is a key performance criterion. DLCs are widely believed to have lower Rf , though these have not been directly compared. Similarly, correct positioning is considered critical although its impact is unclear. We aimed to compare two common bi-caval DLC designs and quantify R f in several positions. Two different commercially available DLCs were sectioned, measured, reconstructed, scaled to 27Fr and simulated in our previously published patient-averaged computational model of the right atrium (RA) and venae cavae at 2–6 L/min. One DLC was then used to simulate ± 30° and ± 60° rotation and ± 4 cm insertion depth. Both designs had low Rf (< 7%) and similar SVC/IVC drainage fractions and pressure drops. Both cannula reinfusion ports created a high-velocity jet and high shear stresses in the cannula (> 413 Pa) and RA (> 52 Pa) even at low flow rates. Caval pressures were abnormally high (16.2–23.9 mmHg) at low flow rates. Rotation did not significantly impact Rf . Short insertion depth increased Rf (> 31%) for all flow rates whilst long insertion only increased Rf at 6 L/min (24%). Our results show that DLCs have lower Rf compared to SLCs at moderate-high flow rates (> 4 L/min), but high shear stresses. Obstruction from DLCs increases caval pressures at low flow rates, a potential reason for increased intracranial hemorrhages. Cannula rotation does not impact Rf though correct insertion depth is critical.
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| 10. |
- Parker, Louis P., et al.
(author)
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Impact of altered vena cava flow rates on right atrium flow characteristics
- 2022
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 132:5, s. 1167-1178
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Journal article (peer-reviewed)abstract
- The right atrium (RA) combines the superior vena cava (SVC) and inferior vena cava (IVC) flows. Treatments like extracorporeal membrane oxygenation (ECMO) and hemodialysis by catheter alter IVC/SVC flows. Here we assess how altered IVC/SVC flow contributions impact RA flow. Four healthy volunteers were imaged with computerized tomography (CT), reconstructed and combined into a patient-averaged model. Large eddy simulations (LESs) were performed for a range of IVC/SVC flow contributions (30%-70% each, increments of 5%) and common flow metrics were recorded. Model sensitivity to reconstruction domain extent, constant/pulsatile inlets, and hematocrit was also assessed. Consistent with literature, a single vortex occupied the central RA across all flowrates with a smaller counter-rotating vortex, not previously reported, in the auricle. Vena cava flow was highly helical. RA turbulent kinetic energy (TKE; P = 0.027) and time-averaged wall shear stress (WSS; P < 0.001) increased with SVC flow. WSS was lower in the auricle (2 Pa, P < 0.001). WSS in the vena cava was equal at IVC/SVC = 65/35%. The model was highly sensitive to the reconstruction domain with cropped geometries lacking helicity in the venae cavae, altering the RA flow. The RA flow was not significantly affected by constant inlets or hematocrit. The commonly reported vortex in in the central RA is confirmed; however, a new, smaller vortex was also recorded in the auricle. When IVC flow dominates, as is normal, TKE in the RA is reduced and WSS in the venae cavae equalize. Significant helicity exists in the vena cava, as a result of distal geometry and this geometry appears crucial to accurately simulating RA flow. NEW & NOTEWORTHY Right atrium turbulent kinetic energy increases as the proportion of flow entering from the superior vena cava is increased. Although the commonly reported large right atrium vortex was confirmed across all flow scenarios, a new smaller vortex is observed in the right auricle. The caval veins exhibit highly helical flow and this appears to be the result of distal venous morphology.
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