scholarly journals Biomarker Profiling in Stage 5 Chronic Kidney Disease Identifies the Relationship between Angiopoietin-2 and Atrial Fibrillation

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 269S-276S ◽  
Author(s):  
Jack Bontekoe ◽  
Justin Lee ◽  
Vinod Bansal ◽  
Mushabbar Syed ◽  
Debra Hoppensteadt ◽  
...  

Atrial fibrillation (AF) is prevalent in nearly 27% of patients with stage 5 chronic kidney disease on hemodialysis (CKD5-HD), suggesting a strong association between these 2 pathologies. It is hypothesized that the relationship between these 2 diseases may be mediated by inflammation. Angiopoietin-2 (Ang-2), a pro-inflammatory biomarker of endothelial instability, inflammation, and vascular remodeling, is elevated in CKD5-HD and AF, yet has not been evaluated in patients with concomitant AF and CKD5-HD. The aim of this study is to analyze circulating levels of inflammatory and thrombotic biomarkers in patients with concomitant AF and CKD5-HD. Plasma levels of Ang-2 were measured via sandwich enzyme-linked immunosorbent assay method in CKD5-HD patients (n = 96), patients with AF (n = 38), and controls (n = 50). Angiopoietin-2 was markedly elevated in CKD5-HD with comorbid AF as compared to CKD5-HD alone, and AF alone, respectively (13.05 ± 1.56 vs 9.57 ± 0.71 ng/mL; P = .00169; vs 2.48 ± 0.57 ng/mL; P < .0001). The results of this study suggest an additive effect of Ang-2 with coexistence of AF and CKD5-HD, which may be useful in the detection of AF within this patient population.

2020 ◽  
Vol 26 ◽  
pp. 107602962093222 ◽  
Author(s):  
Jack Bontekoe ◽  
Vinod Bansal ◽  
Justin Lee ◽  
Mushabbar Syed ◽  
Debra Hoppensteadt ◽  
...  

Cardiovascular disease and infection are the leading causes of mortality in patients with stage 5 chronic kidney disease on hemodialysis (CKD5-HD). Inflammation is a large component in the pathogenesis of both atrial fibrillation (AF) and sepsis and may link these conditions in CKD5-HD. Procalcitonin (PCT) is an inflammatory biomarker elevated in systemic infection and CKD5-HD, yet its value with regard to comorbid AF has not been thoroughly investigated. The aim of this study sought to evaluate circulating inflammatory markers, including PCT, Angiopoietin-1, Angiopoetin-2, CD40-L, C-reactive protein, d-dimer, and von Willebrand factor in relation to these conditions. Plasma levels of inflammatory markers were measured by enzyme linked immunosorbent assay method in CKD5-HD (n = 97) patients and controls (n = 50). Procalcitonin levels were significantly elevated ( P = .0270) in CKD5-HD with comorbid AF compared to those without AF. Further analysis of patients with a history of sepsis demonstrated significantly elevated levels of PCT ( P = .0405) in those with comorbid AF (160.7 ± 39.5 pg/mL) compared to those without AF (117.4 ± 25.3 pg/mL). This study demonstrates that the inflammatory biomarker PCT is further elevated in the presence of both AF and a history of sepsis in hemodialysis patients and suggests that underlying chronic inflammation following sepsis resolution may place these patients at greater risk of developing AF.


Author(s):  
Atsuko Kamijo-Ikemori ◽  
Takeshi Sugaya ◽  
Maki Yoshida ◽  
Seiko Hoshino ◽  
Satoshi Akatsu ◽  
...  

AbstractBackground:Urinary liver-type fatty acid binding protein (L-FABP) measured by enzyme-linked immunosorbent assay method (ELISA) was approved as a clinical biomarker of tubular damage by the Japanese Ministry of Health, Labor and Welfare (MHLW) in 2011. We evaluated a new latex-enhanced immunoturbidimetric assay (LTIA) to evaluate the clinical utility of urinary L-FABP measured by LTIA versus an ELISA assay.Methods:LTIA with anti-human L-FABP mouse monoclonal antibodies was performed using an automated clinical chemistry analyzer. Five positive samples with low, medium and high L-FABP concentrations were analyzed to determine the within-run precision. In patients with chronic kidney disease (CKD) (n=91), urinary L-FABP levels were measured by ELISA and LTIA.Results:Measurement of urinary L-FABP revealed urinary L-FABP levels within 30 min. The within-run coefficient of variation was 10.0% for 1.4 ng/mL, 4.4% for 2.5 ng/mL, 3.2% for 9.8 ng/mL, 1.5% for 50.1 ng/mL, and 1.2% for 102.7 ng/mL. Concentrations of urinary L-FABP measured by LTIA were significantly correlated with those measured by ELISA (ρ=0.932). Proportional systematic error was almost within limits of agreement (LOA). Urinary L-FABP levels measured by LTIA were significantly correlated with urinary albumin (ρ=0.634), urinary NAG (ρ=0.688) and eGFR (ρ=–0.561).Conclusions:Measurement of urinary L-FABP by LITA was simple, speedy, and similar in quality to ELISA results. Therefore, this method was approved as external body diagnosing medicines by the Japanese MHLW in 2014. Urinary L-FABP is expected to be widely used in various pathophysiological conditions by measuring urinary L-FABP using LTIA.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Esther D Kim ◽  
Ning Ding ◽  
Junichi Ishigami ◽  
Xuejuan Ning ◽  
Yijing Feng ◽  
...  

Background: Chronic kidney disease (CKD) strongly predicts sudden cardiac death and may elevate the risk of certain cardiac arrhythmias like atrial fibrillation; however, the relationships between CKD and various types of arrhythmia are not well-characterized. Methods: We performed a systematic review and meta-analysis by searching Embase and PubMed for prospective, cross-sectional, and case-control studies examining the associations of two key CKD measures, estimated glomerular filtration rate (eGFR) and albuminuria, with arrhythmias in adults that were published until July 2018. We performed qualitative assessment of studies using the Newcastle Ottawa Quality Assessment Scale. We pooled the results using random-effects models. Results: Among 16,245 articles, we identified 34 prospective (n=24,213,233), 21 cross-sectional (n=253,328), and 4 case-control (n=1,694) studies that included diverse study populations from 19 countries and were mostly high quality. Most prospective studies examined the relationship between eGFR and atrial fibrillation (AF), and demonstrated that lower eGFR was associated with a higher risk of AF (pooled hazard ratio [HR] 1.72 [95% CI: 1.30, 2.27] comparing reduced vs. referent eGFR groups)[ Figure ]. A few studies examined albuminuria and demonstrated its associations with AF (pooled HR 2.16 [95% CI: 1.74, 2.67] comparing high vs. low albuminuria). Results were similar for cross-sectional studies. Four prospective studies reported a higher incidence of ventricular tachycardia resulting in ICD shock according to reduced eGFR (pooled HR 2.32 [95% CI: 1.74, 3.09] comparing reduced vs. referent eGFR groups). Limited number of studies examined other types of arrhythmia. Conclusion: We identified robust data on the relationship between CKD (eGFR and albuminuria) and AF. Reduced eGFR was associated with life-threatening ventricular arrhythmias. Our review highlights the need of future studies for non-AF arrhythmias, especially in the context of albuminuria.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kamila Olimxanova

Abstract Background and Aims Currently, it is estimated that the intestinal microbiota has hundreds of species of bacteria. It is known that intestinal dysbiosis contributes to the development of many diseases, such as obesity, diabetes mellitus, cardiovascular diseases, including CKD. The question of the relationship between bacterial contamination and the process of endogenous inflammation in patients with chronic kidney disease of the pre-dialysis stages is not completely clear. The aim of the study the composition of the intestinal microbiota in fecal samples and the level of inflammatory markers (CRP, IL-6, leukocytes) in patients with pre-dialysis stages of CKD. Method 60 patients with CKD of the pre-dialysis stages (C2-C4) were examined. The diagnosis of CKD was made on the basis of clinical, instrumental, and laboratory data. To study the relationship between the composition of the intestinal microbiota and inflammation in patients with CKD, we studied markers of inflammation such as CRP and IL-6. CRP was determined in blood serum by a highly sensitive method on a Humareader Single analyzer, IL-6 by enzyme-linked immunosorbent assay on a solid-phase analyzer. eGFR was calculated using the formula CKD-EPI-2011. The control group consisted of 30 healthy subjects. Statistical processing was carried out using methods of variation statistics. The results were processed using Microsoft Exel 2002 & Statistica 6.0. Results The average age of patients was 59 years. Of these, 25 women (40%) and 35 (60%) men. The estimated glomerular filtration rate varied from 30 to 60 ml / min / 1.73 m2, which corresponded to the indicators of the pre-dialysis stages of CKD. Analysis of intestinal microbiota showed a deficiency of Bifidobacterium bacteria (&lt;108 CFU), and an increase in the number of Escherichia (&gt; 108 CFU) in patients with CKD of the pre-dialysis stages. According to the results of the study, in the group of patients with CKD, the level of inflammatory markers was higher (CRP-55%, IL-6-60%, leukocytes 62%) than in the control group (CRP-45%, IL-6-40%, leukocytes 38% ) However, in men, the IL-6 index was higher than in women. In patients with CKD with obesity, the titer of pathogenic bacteria and their spectrum showed the worst results, although unreliable. Conclusion All examined patients had dysbiosis of the 2nd degree. At the same time, an imbalance of the intestinal microbiota is combined with an increased level of CRP, IL-6, and white blood cells.


2016 ◽  
Vol 14 (3) ◽  
pp. 260-265 ◽  
Author(s):  
Beata Franczyk ◽  
Anna Gluba-Brzózka ◽  
Aleksandra Cia|kowska-Rysz ◽  
Maciej Banach ◽  
Jacek Rysz

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Benson J. Ouma ◽  
Paul Bangirana ◽  
John M. Ssenkusu ◽  
Dibyadyuti Datta ◽  
Robert O. Opoka ◽  
...  

Abstract Background Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated. Methods Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini–Hochberg Procedure of False Discovery Rate. Results Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode. Conclusion Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.M Andreu Cayuelas ◽  
S Raposeiras-Roubin ◽  
E Fortuny Frau ◽  
A Garcia Del Egido ◽  
J Seller-Moya ◽  
...  

Abstract Introduction Chronic kidney disease (CKD) is associated with an elevated thromboembolic and bleeding risk in atrial fibrillation (AF) patients, so the decision of antithrombotic therapy is a challenge. Purpose To analyze mortality, embolic and bleeding events in patients with advanced CKD and AF. Methods Multicentric retrospective registry on patients with AF and advanced CKD (CKD-EPI &lt;30 mL/min/1.73 m2). For death, multivariable Cox regression analysis was developed. For embolic and bleeding events, competing-risks regression based on Fine and Gray's proportional subhazards model was performed, being death the competing event Results We analysed 405 patients with advanced CKD and newly diagnosed AF. 57 patients were not treated with antithrombotic therapy (14.1%), 80 only with antiplatelet/s (19.8%), 211 only with anticoagulation (52.1%), and 57 with anticoagulant plus antiplatelet/s (14.1%). During a follow-up of 4.6±2.5 years, 205 died (50.6%), 34 had embolic events (8.4%) and 85 had bleeding outcomes (21.0%). Bleeding event rate was significantly lower in patients without antithrombotic therapy (Figure). After multivariate analysis, anticoagulant treatment was associated with higher bleeding rates, without differences in mortality or embolic events (Table). Conclusion Anticoagulation therapy was associated with a significant increase in bleeding events in patients with advanced CKD and newly diagnosed AF. None of the antithrombotic therapy regimens resulted in lower embolic events rate neither benefit in mortality. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by an unconditional grant from BMS-Pfizer


Endocrine ◽  
2021 ◽  
Author(s):  
Walter Reinhardt ◽  
Nils Mülling ◽  
Stefan Behrendt ◽  
Sven Benson ◽  
Sebastian Dolff ◽  
...  

Abstract Purpose The relationship between proteinuria and thyroid function remains controversial in patients with chronic kidney disease (CKD). We prospectively investigated the association between kidney and thyroid function in thyroid antibody-negative patients through all CKD stages. Methods We enrolled 184 nondialysis patients (mean age: 63.1 ± 16.9 years) without previous thyroid disease or thyroid-specific antibodies. Kidney function was assessed by estimating the glomerular filtration rate (eGFR) classified according KDIGO (CKD G1–5). Kidney damage was assessed by albuminuria (albumin-to-creatinine ratio, ACR) and classified as mild, moderate, or severe (ACR1: <300, ACR2: 300–3000, and ACR3: 3000 mg/g). To evaluate thyroid function, TSH, T4, fT4, T3, fT3, reverse T3 (rT3), and thyroxine-binding globulin (TBG) were measured. Results rT3 concentrations correlated negatively with albuminuria (r = −0.286, p < 0.001) and were significantly lower in patients with severe albuminuria than in those with mild or moderate albuminuria (ACR3: 0.28 vs. ACR2: 0.32 vs. ACR1: 0.36 nmol/l, p < 0.001). The severity of albuminuria revealed no impact on TSH, fT4, T3, fT3, and TBG. EGFR correlated with increasing T4, fT4, T3, fT3, and TBG (T4: r = 0.289, p < 0.01; fT4: r = 0.196, p < 0.01; T3: r = 0.408, p < 0.01; fT3: r = 0.390, p < 0.01) but not with rT3. Conclusions In thyroid antibody-negative patients presenting advanced CKD (stages 4 and 5), even severe kidney protein loss failed to influence thyroid hormone status. However, albuminuria severity correlated negatively with rT3, which was significantly lower in patients with albuminuria in the nephrotic range.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hamatani ◽  
M Iguchi ◽  
Y Aono ◽  
K Ishigami ◽  
S Ikeda ◽  
...  

Abstract Background Atrial fibrillation (AF) increases the risk of death, stroke/systemic embolism and heart failure (HF). Plasma natriuretic peptide (NP) level is an important prognostic marker in HF patients. However, little is known regarding the prognostic significance of plasma NP level in AF patients without HF. Purpose The aim of this study is to investigate the relationship between plasma NP level and clinical outcomes such as all-cause death, stroke/systemic embolism and HF hospitalization during follow-up period in AF patients without HF. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in our city. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. From the registry, we excluded 1,220 patients without a pre-existing HF (defined as having one of the following; prior hospitalization for HF, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%). Among 3,246 AF patients without HF, we investigated 1,189 patients with the data of plasma BNP (n=401) or N-terminal pro-BNP (n=788) level at the enrollment. We divided the patients according to the quartile of each plasma BNP or NT-pro BNP level and compared the backgrounds and outcomes between these 4 groups stratified by plasma NP level. Results Of 1,189 patients, the mean age was 72.1±10.2 years, 454 (38%) were female and 684 (58%) were paroxysmal AF. The mean CHADS2 and CHA2DS2-VASc score were 1.6±1.1 and 2.9±1.5, respectively. Oral anticoagulants were prescribed in 671 (56%) at baseline. The median (interquartile range) BNP and N-terminal pro-BNP level were 84 (38, 176) and 500 (155, 984) pg/ml, respectively. Patients with high plasma NP level were older, and demonstrated lower prevalence of paroxysmal AF, higher CHADS2 and CHA2DS2-VASc scores and higher prevalence of chronic kidney disease and oral anticoagulants prescription (all P&lt;0.01). A total of 165 all-cause death, 114 stroke/systemic embolism and 103 HF hospitalization occurred during the median follow-up period of 5.0 years. Kaplan-Meier curves demonstrated that higher plasma NP level was significantly associated with the incidences of all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF (Figure 1A). Multivariable Cox regression analysis revealed that plasma NP level could stratify the risk of clinical outcomes even after adjustment by type of AF, CHA2DS2-VASc score, chronic kidney disease and oral anticoagulant prescription (Figure 1B). Conclusion Plasma NP level is a significant prognostic marker for all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF, suggesting the importance of measuring plasma NP level in AF patients even without HF. Figure 1 Funding Acknowledgement Type of funding source: None


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