scholarly journals Biomarker Profiling of Neurovascular Diseases in Patients with Stage 5 Chronic Kidney Disease

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 248S-254S
Author(s):  
Justin Lee ◽  
Jack Bontekoe ◽  
Brandon Trac ◽  
Vinod Bansal ◽  
José Biller ◽  
...  

Patients with stage 5 chronic kidney disease (CKD5D) have a higher risk of developing neurocognitive deficits. Stroke, cervical carotid artery disease (CCAD), and intracranial atherosclerotic disease (ICAD) are causes of such deficits in CKD5D. Chronic inflammation from renal failure elevates risk for these diseases through oxidative stress and vascular dysfunction. The adverse impact on the carotid and intracranial vasculatures contributes to the multifactorial pathophysiology of stroke. Eleven plasma biomarker levels in patients with CKD5D (n = 97) and healthy controls (n = 17-50) were measured using sandwich enzyme-linked immunosorbent assay (ELISA) method. Of the 97 patients with CKD5D, 24 had CCAD, 19 had ICAD, and 23 had acute stroke. Elevations in NACHT, LRR, and PYD domains-containing protein 3 (NALP3) levels in patients with CKD5D (+)CCAD (1.80 ± 0.11 ng/mL) compared to patients with (−)CCAD (1.55 ± 0.08 ng/mL) were statistically significant ( P = .0299). Differences in D-dimer levels were also found to be statistically significant ( P = .0258) between CKD5D (+)stroke (1.83 ± 0.42 μg/mL) and (−)stroke (0.89 ± 0.13 μg/mL) groups. The ages of the (+) neurovascular disease groups were found to be significantly elevated compared to the (−) neurovascular disease groups ( P = .0002 carotid AD; P < .0001 ICAD; P = .0157 stroke). D-dimer levels were positively correlated with age in CKD5D ( P = .0375). With the possible exception of NALP3 for CCAD, profiling levels of specific biomarkers for risk stratification of neurovascular diseases in the CKD5D population warrants further investigation.

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 314S-322S
Author(s):  
Justin Lee ◽  
Ryan McMillan ◽  
Leonidas Skiadopoulos ◽  
Vinod Bansal ◽  
José Biller ◽  
...  

The prevalence of neurocognitive deficits remains high in patients with stage 5 chronic kidney disease (CKD5D). Major contributors to such deficits include stroke, cervical carotid artery disease (CCAD), and intracranial atherosclerotic disease (ICAD). The risk of developing these dysfunctional vascular processes is facilitated by the chronic inflammation associated with renal failure. Plasma levels of 10 circulating biomarkers in patients with CKD5D (n = 78-90) were quantified using the sandwich enzyme linked immune sorbent assay method. Biomarkers for this study included kidney injury molecule-1, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), neutrophil gelatinase-associated lipocalin, interleukin-18, endothelin 1, calcifediol, parathyroid hormone, platelet-derived growth factor, microparticles-expressing tissue factor, and lipoprotein(a) (Lp(a)). Of the 90 patients with CKD5D, 30 had CCAD, 24 had ICAD, and 22 had stroke. Lp(a) level was significantly elevated in patients with CKD5D with comorbid ICAD compared to those without (125.70 ± 10.03 ng/mL vs 97.16 ± 5.97 ng/mL; P = .0065). NT-proBNP level was also significantly elevated in patients with CKD5D with comorbid stroke diagnosis compared to those without stroke history, once patients with a diagnosis of heart failure (HF) were excluded (14.84 ± 2.80 ng/mL vs 9.06 ± 1.27 ng/mL; P = .0283). Profiling levels of Lp(a) and NT-ProBNP could thus be useful in the risk stratification of ICAD and stroke, respectively, in the CKD5D population.


2017 ◽  
Vol 46 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Farsad Afshinnia ◽  
Lixia Zeng ◽  
Jaeman Byun ◽  
Crystal A. Gadegbeku ◽  
Maria Chiara Magnone ◽  
...  

Background: The role of myeloperoxidase in chronic kidney disease (CKD) and its association with coronary artery disease (CAD) is controversial. In this study, we compared myeloperoxidase and protein-bound 3-chlorotyrosine (ClY) levels in subjects with varying degrees of CKD and tested their associations with CAD. Methods: From Clinical Phenotyping Resource and Biobank Core, 111 patients were selected from CKD stages 1 to 5. Plasma myeloperoxidase level was measured using enzyme-linked-immunosorbent assay. Plasma protein-bound 3-ClY, a specific product of hypochlorous acid generated by myeloperoxidase was measured by liquid chromatography mass spectrometry. Results: We selected 29, 20, 24, 22, and 16 patients from stages 1 to 5 CKD, respectively. In a sex-adjusted general linear model, mean ± SD of myeloperoxidase levels decreased from 18.1 ± 12.3 pmol in stage 1 to 10.9 ± 4.7 pmol in stage 5 (p = 0.011). In patients with and without CAD, the levels were 19.1 ± 10.1 and 14.8 ± 8.7 pmol (p = 0.036). There was an increase in 3-ClY mean from 0.81 ± 0.36 mmol/mol-tyrosine in stage 1 to 1.42 ± 0.41 mmol/mol-tyrosine in stage 5 (p < 0.001). The mean 3-ClY levels in patients with and without CAD were 1.25 ± 0.44 and 1.04 ± 0.42 mmol/mol-tyrosine (p = 0.023), respectively. C-statistic of ClY when added to myeloperoxidase level to predict CKD stage 5 was 0.86, compared to 0.79 for the myeloperoxidase level alone (p = 0.0097). Conclusion: The myeloperoxidase levels decrease from stages 1 to 5, whereas activity increases. In contrast, both myeloperoxidase and ClY levels rise in the presence of CAD at various stages of CKD. Measuring both plasma myeloperoxidase and 3-CLY levels provide added value to determine the burden of myeloperoxidase-mediated oxidative stress.


2018 ◽  
Vol 69 (8) ◽  
pp. 2064-2066
Author(s):  
Mircea Munteanu ◽  
Adrian Apostol ◽  
Viviana Ivan

The aim of the present study is to investigate the prevalance of chronic kidney disease (CKD), of cardiovascular disease (CVD) and dyslipidemia in patients with diabetes mellitus (DM). We conducted a prospective, controlled study involving 420 diabetic patients (120 T1DM, 300 T2DM) and investigate the following aspects: the presence of vascular complications (stroke, coronary artery disease, peripheral artery disease), lipid profile (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), kidney function (glomerular filtration rate, albuminuria), blood pressure, HbA1C. The results that in diabetic patients with CKD there is an increased prevalence of CVD and of dislipidemia. Also we noticed a negative correlation between total cholesterol level and decease in eGFR in all patients, with or without CKD.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ozan Dikilitas ◽  
Benjamin A Satterfield ◽  
Maya Safarova ◽  
Shoa L Clarke ◽  
Catherine Tcheandjieu ◽  
...  

Background: The pathophysiology of lipoprotein (a) [Lp(a)] remains obscure. We conducted a phenome wide analysis study (PheWAS) to identify pleiotropic effects of LPA variants. Methods: Among 51,843 European-ancestry participants (age 58±16 years, 54% female) of the electronic MEdical Records and Genomics (eMERGE) network we assessed whether LPA variants exhibited pleiotropic affects through an electronic health record-based PheWAS. We adjusted significant associations by presence of atherosclerotic cardiovascular disease (ASCVD; defined as a composite of coronary heart disease, cerebrovascular disease, and peripheral artery disease) to determine whether those associations were independent of ASCVD. Results: In PheWAS analysis, we tested 864 phecodes with 36 independent LPA variants. We identified 21 significant associations with non-ASCVD phenotypes including heart failure, aortic valve stenosis, and chronic kidney disease of which 14 were replicated across independent cohorts. The strength of associations between the LPA variant rs10455872 and both heart failure and aortic valve stenosis related phecodes were significantly attenuated after adjustment for ASCVD. However, the association with chronic kidney disease phecode remained independent following adjustment for ASCVD without any attenuation in the estimated odds ratio (Table). Conclusions: LPA genetic variants were associated with aortic valve stenosis, heart failure and chronic kidney disease. The observed association of LPA variant rs10455872 with aortic stenosis and heart failure appear to be partially mediated by ASCVD, while the association with chronic kidney disease appears to be independent of ASCVD. Additional studies are needed to elucidate potential mechanisms by which Lp(a) may contribute to the pathogenesis of non-ASCVD disease phenotypes.


Author(s):  
Tamara Muratovna Khokonova ◽  
Zaira Feliksovna Kharaeva ◽  
Rustam Khasanovich Keshokov ◽  
Sofiat Khasenovna Sizhazheva ◽  
Svetlana Sergeevna Solyanik

The effect of antihypertensive and hypolipidemic therapy with the use of a fixed combination of amlodipine, lisinopril and rosuvastatin on the parameters of cytokines (the level of the proinflammatory cytokine - interleukin-1β, anti-inflammatory cytokine - interleukin-10, ligand CD40 (CD40L)), central aortic pressure, arterial stiffness and the value of albuminuria in patients with stage 3 chronic kidney disease, both in combination with arterial hypertension (AH) of 1-2 degrees, and without it, and in patients with coronary artery disease in combination with AH. The results of the study allow to conclude that the proposed antihypertensive and hypolipidemic therapy significantly reduces the parameters of central hemodynamics and vascular stiffness, the levels of microalbuminuria (MAU) and blood creatinine in patients with stage 3 chronic kidney disease in combination with AH of 1-2 degrees, and significantly increases the values IL-10 in patients with hypertension and CKD.


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.


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