scholarly journals Retinal endothelial dysfunction: A glance on long-term risk of kidney failure

Antonio Bellasi ◽  
Davide Salera ◽  
Luca Di Lullo
2021 ◽  
Vol 8 ◽  
pp. 205435812110297
Jean Maxime Côté ◽  
Isabelle Ethier ◽  
Héloïse Cardinal ◽  
Marie-Noëlle Pépin

Background: Chronic kidney disease following liver transplantation is a major long-term complication. Most liver transplant recipients with kidney failure will be treated with dialysis instead of kidney transplantation due to noneligibility and shortage in organ availability. In this population, the role of peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) remains unclear. Objective: To determine the feasibility regarding safety, technique survival, and dialysis efficiency of PD in liver transplant recipients requiring KRT for maintenance dialysis. Design: Systematic review. Setting: Interventional and observational studies reporting the use of PD after liver transplantation. Patients: Adult liver transplant recipients with kidney failure treated with maintenance KRT. Measurements: Extracted data included eligibility criteria, study design, demographics, and PD modality. The following outcomes of interest were extracted: rate of peritonitis and microorganisms involved, noninfectious peritoneal complications, technique survival, and kidney transplantation-censored technique survival. Non-PD complications included overall survival, liver graft dysfunction, and hospitalization rate. Methods: The following databases were searched until July 2020: MedLine/PubMed, EMBASE, CINAHL, and Cochrane Library. Two reviewers independently screening all titles and abstracts of all identified articles. Due to the limited sample size, observational designs and study heterogeneity expected, no meta-analysis was pre-planned. Descriptive statistics were used to report all results. Results: From the 5263 identified studies, 4 were included in the analysis as they reported at least 1 outcome of interest on a total of 21 liver transplant recipients, with an overall follow-up duration on PD of 19.0 (Interquartile range [IQR]: 9.5-29.5) months. Fifteen episodes of peritonitis occurred in a total cumulative PD follow-up of 514 patient-months, representing an incidence rate of 0.35 per year. These episodes did not result in PD technique failure, mortality, or impairment of liver graft function. Limitations: Limitations include the paucity of studies in the field and the small number of patients included in each report, a risk of publication bias and the impossibility to directly compare hemodialysis to PD in this population. These results, therefore, must be interpreted with caution. Conclusions: Based on limited data reporting the feasibility of PD in liver transplant recipients with kidney failure, no signal was associated with an increased risk of infectious complications. Long-term studies evaluating this modality need to be performed. Registration (PROSPERO): CRD42020218374.

2021 ◽  
Vol 16 (1) ◽  
J. Víšek ◽  
M. Bláha ◽  
V. Bláha ◽  
M. Lášticová ◽  
M. Lánska ◽  

Abstract Background Lipoprotein apheresis (LA) is considered as an add-on therapy for patients with familial hypercholesterolemia (FH). We aimed to analyze the data collected in the last 15 years from FH patients treated with LA, to elucidate the benefit of this procedure with respect to plasma lipids, biomarkers of inflammation, and endothelial dysfunction and soluble endoglin. Results 14 patients (10 heterozygous FH patients (HeFH), 4 homozygous FH patients (HoFH)) were treated by long-term lipoprotein apheresis. Lipid levels were examined, and ELISA detected biomarkers of inflammation and soluble endoglin. Paired tests were used for intergroup comparisons, and a linear regression model served to estimate the influence of the number of days patients were treated with LA on the studied parameters. LA treatment was associated with a significant decrease of total cholesterol (TC), LDL-C, HDL-C, and apoB, in both HeFH and HoFH patients, after single apheresis and in a long-term period during the monitored interval of 15 years. Biomarkers of inflammation and endothelial dysfunction were reduced for soluble endoglin, hsCRP, and MCP-1, and sP-selectin after each procedure in some HeFH and HoFH patients. Conclusions LA treatment up to 15 years, reduced cholesterol levels, levels of biomarkers related to endothelial dysfunction, and inflammation not only after each procedure but also in the long-term evaluation in FH patients. We propose that long-term LA treatment improves lipid profile and endothelial dysfunction in familial hypercholesterolemia patients, suggesting a promising improvement in cardiovascular prognosis in most FH patients.

Michał Harańczyk ◽  
Małgorzata Konieczyńska ◽  
Wojciech Płazak

Abstract Purpose Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular diseases. The aim of the study was to assess the influence of OSAS on endothelial dysfunction and thrombosis biomarkers and to evaluate the effect of treatment with continuous positive airway pressure (CPAP) on biomarker levels. Methods NT-proBNP, sICAM-1, endothelin-1, von Willebrand factor, D-dimers, and thrombin-antithrombin complex (TAT) were measured in 50 patients diagnosed with moderate-to-severe OSAS. All patients underwent transthoracic echocardiography, and 38 months after the inclusion, 16 CPAP users and 22 non-CPAP users were reassessed. Results Sleep-related indices of apnea-hypopnea index (AHI) and mean SpO2 were associated with higher sICAM-1 levels (AHI < 30: 7.3 ± 4.7 vs. AHI ≥ 30: 19.5 ± 19.4 mg/ml, p = 0.04; SpO2 ≥ 90%: 11.9 ± 9.3 vs. SpO2 < 90%: 23.6 ± 25.8, p = 0.04). sICAM-1 levels were significantly higher in obese patients, particularly with BMI ≥ 40. Plasma levels of TAT were significantly correlated with the increased right ventricular size (right ventricular diameter ≤ 37 mm: 0.86 ± 0.70 vs. > 37 mm: 1.96 ± 1.20 ng/ml, p = 0.04). Endothelin-1 levels were higher in patients with decreased right ventricular function (right ventricle TDI-derived S′ ≥ 12 cm/s: 11.5 ± 10.9 vs. < 12 cm/s: 26.0 ± 13.2 pg/ml, p = 0.04). An increase in NT-proBNP was related to impaired parameters of the right ventricular contractile function. There were no correlations between long-term CPAP therapy and the levels of biomarkers. Conclusion Severe OSAS influences endothelial damage as manifested by an increase in sICAM-1 levels. Changes in right ventricular structure and function, observed mainly in patients with higher TAT and endothelin-1 levels, are also manifested by an increase in NT-proBNP levels. Long-term CPAP treatment does not seem to influence biomarkers in patients with moderate-to-severe OSAS, which may help to explain the lack of influence of CPAP on cardiovascular risk reduction.

Ferdows Atiq ◽  
Jens van de Wouw ◽  
Oana Sorop ◽  
Ilkka Heinonen ◽  
Moniek P. M. de Maat ◽  

AbstractIt is well known that high von Willebrand factor (VWF) and factor VIII (FVIII) levels are associated with an increased risk of cardiovascular disease. It is still debated whether VWF and FVIII are biomarkers of endothelial dysfunction and atherosclerosis or whether they have a direct causative role. Therefore, we aimed to unravel the pathophysiological pathways of increased VWF and FVIII levels associated with cardiovascular risk factors. First, we performed a randomized controlled trial in 34 Göttingen miniswine. Diabetes mellitus (DM) was induced with streptozotocin and hypercholesterolemia (HC) via a high-fat diet in 18 swine (DM + HC), while 16 healthy swine served as controls. After 5 months of follow-up, FVIII activity (FVIII:C) was significantly higher in DM + HC swine (5.85 IU/mL [5.00–6.81]) compared with controls (4.57 [3.76–5.40], p = 0.010), whereas VWF antigen (VWF:Ag) was similar (respectively 0.34 IU/mL [0.28–0.39] vs. 0.34 [0.31–0.38], p = 0.644). DM + HC swine had no endothelial dysfunction or atherosclerosis during this short-term follow-up. Subsequently, we performed a long-term (15 months) longitudinal cohort study in 10 Landrace–Yorkshire swine, in five of which HC and in five combined DM + HC were induced. VWF:Ag was higher at 15 months compared with 9 months in HC (0.37 [0.32–0.42] vs. 0.27 [0.23–0.40], p = 0.042) and DM + HC (0.33 [0.32–0.37] vs. 0.25 [0.24–0.33], p = 0.042). Both long-term groups had endothelial dysfunction compared with controls and atherosclerosis after 15 months. In conclusion, short-term hyperglycemia and dyslipidemia increase FVIII, independent of VWF. Long-term DM and HC increase VWF via endothelial dysfunction and atherosclerosis. Therefore, VWF seems to be a biomarker for advanced cardiovascular disease.

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
William H Stewart ◽  
Eric George ◽  
Gene L Bidwell ◽  
Heather Chapman ◽  
Fakhri Mahdi ◽  

Background: Preeclampsia is a major obstetrical health concern, affecting 5-8% of all pregnancies. Hallmarked by hypertension and endothelial dysfunction the origin of the disease remains obscure, though it is generally accepted that placental insufficiency/ischemia is a central cause. In response, the placenta secretes pathogenic factors, in particular the anti-angiogenic protein sFlt-1. Currently, there is no effective therapy for the management of the preeclampsia patient. We have recently produced a novel synthetic peptide based on placental growth factor (PlGF) which is maternally restricted by fusion to the synthetic carrier elastin like polypeptide (ELP). Here, we describe its in vivo pharmacokinetics and biodistribution. Methods: Fluorescently labeled ELP-PLGF was administered i.v. and blood sampled serially to determine clearance kinetics. Long-term pharmacokinetics and biodistribution was performed after subcutaneous administration of labeled peptide. Measurements were made on serially drawn blood, and in the whole animal by in vivo imaging. Results: ELP-PlGF exhibited markedly more favorable pharmacokinetics than the normal half life of PlGF, with a terminal half-life of ~10 hours as opposed to ~30 minutes for PlGF alone. Chronic administration found highest levels accumulating in placenta and kidney (two favorable targets for preeclampsia) and liver. A single subcutaneous administration at 100mg/kg resulted in sustained therapeutic plasma concentrations for over 10 days. Conclusion: These data demonstrate that ELP-PlGF has favorable pharmacokinetic and biodistribution profiles. Previous data suggest ELP-PlGF directly antagonizes sFlt-1 in culture. Future studies to assess the in vivo effectiveness of ELP-PlGF in managing placental ischemia induced hypertension and endothelial dysfunction are currently in progress. Acknowledgment: This work was supported by NIH grants R0121527 (GLB), T32HL105324 (OCL), P01HL51971, P20GM104357 (EMG), and R00HL116774 (EMG)

2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A339-A339
J Fernandez-Mendoza ◽  
Z Gao ◽  
K Brandt ◽  
L Houser ◽  
S L Calhoun ◽  

Abstract Introduction Sleep disordered breathing (SDB) in middle-age is an established risk factor for cardiovascular disease. However, population-based studies supporting its cardiovascular contribution at earlier stages of development are lacking, particularly with long-term follow-ups. Methods The Penn State Child Cohort is a population-based longitudinal sample of 700 children (8.7±1.7y), of whom 421 were followed-up 8.3 years later during adolescence (17.0±2.3y) with in-lab polysomnography (PSG). To date, 425 have been followed-up another 7.4 years later during young adulthood (24.4±2.6y) via a standardized survey and 136 of them (55.1% female, 21.3% racial/ethnic minority) have undergone a repeat of their PSG to ascertain apnea/hypopnea index. Subjects (n=121) also underwent Doppler ultrasounds to assess flow-mediated dilation (FMD) and carotid intima-media thickness (CIMT). Linear regression models stratified by body mass index in young adulthood. Results SDB was cross-sectionally associated with lower FMD (β=-0.239, p=0.008) and greater CIMT (β=0.330, p&lt;0.001) in young adulthood. Longitudinally, childhood (n=121) and adolescence (n=90) SDB were significantly associated with CIMT (β=0.327, p&lt;0.001 and β=0.286, p=0.006, respectively), but not with FMD (β=-0.158, p=0.08 and β=-0.101, p=0.35, respectively). These associations, particularly longitudinal ones between childhood and adolescence SDB with CIMT in young adulthood, were stronger in overweight than normal weight subjects (e.g., β=0.310, p=0.030 and β =0.089, p=0.582, respectively). Conclusion SDB and obesity appear to be synergistically associated with endothelial dysfunction and atherosclerosis in young adults from the general population. These data suggest that a childhood exposure to chronic SDB is associated with long-term atherosclerosis, while endothelial dysfunction may be a short-term outcome. This ongoing 16-year longitudinal study will test whether the natural history of SDB from childhood through adolescence into young adulthood shows differential trajectories for cardiovascular morbidity. Support National Institutes of Health (R01HL136587, R01HL97165, R01HL63772, UL1TR000127)

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