scholarly journals Urea, a true uremic toxin: the empire strikes back

2016 ◽  
Vol 131 (1) ◽  
pp. 3-12 ◽  
Author(s):  
Wei Ling Lau ◽  
Nosratola D. Vaziri
Keyword(s):  
Heart Disease ◽  
Kidney Function ◽  
Kidney Failure ◽  
Waste Product ◽  
Adverse Outcomes ◽  
Toxic Effects ◽  
Blood Levels ◽  
Uremic Toxin ◽  
Metabolic Waste Product

Decreased kidney function results in high blood levels of urea, a metabolic waste product. In this review we discuss urea's direct and indirect toxic effects that may promote adverse outcomes including progression of kidney failure and heart disease.

Phytoestrogen blood levels and adverse outcomes in women with suspected ischemic heart disease

2020 ◽  
Author(s):  
Lili Barsky ◽  
Galen Cook-Wiens ◽  
Mark Doyle ◽  
Chrisandra Shufelt ◽  
William Rogers ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Adverse Outcomes ◽  
Ischemic Heart ◽  
Blood Levels

577 Engineered non-pathogenic synthetic biotic producing L-arginine synergize with PD-1-based cancer immunotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A611-A611
Author(s):  
Fernando Canale ◽  
Camilla Basso ◽  
Ning Li ◽  
Anna Sokolovska ◽  
Michela Perotti ◽  
...  
Keyword(s):  
T Cells ◽  
Synergistic Effects ◽  
Waste Product ◽  
T Cell Response ◽  
Escherichia Coli Nissle 1917 ◽  
Check Point Inhibitors ◽  
Blocking Antibodies ◽  
Metabolic Waste Product ◽  
Synthetic Biology Approach ◽  
Escherichia Coli Nissle

BackgroundThe availability of L-arginine in tumors is a key determinant of an efficient anti-tumor T cell response. Consequently, the elevation of typically low L-arginine levels within the tumor may greatly potentiate the anti-tumor responses of immune check point inhibitors, such as PD-L1 blocking antibodies. However, currently no means are available to locally increase intra-tumoral L-arginine levels.MethodsWe used a synthetic biology approach to develop an engineered probiotic Escherichia coli Nissle 1917 strain that colonizes tumors and continuously converts ammonia, a metabolic waste product that accumulates in tumors, into L-arginine.ResultsColonization of tumors with these bacteria elevated intra-tumoral L-arginine concentrations, increased the amount of tumor-infiltrating T cells, and had striking synergistic effects with PD-L1 blocking antibodies in the clearance of tumors. The anti-tumor effect of the living therapeutic was mediated by L-arginine and was dependent on T cells.ConclusionsThese results show that engineered microbial therapies enable metabolic modulation of the tumor microenvironment leading to enhanced efficacy of immunotherapies.

Abstract 17220: Effects of the Oral Adsorbent of AST-120 in Patients with both Chronic Heart Failure and Chronic Kidney Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Miki Imazu ◽  
Masanori Asakura ◽  
Takuya Hasegawa ◽  
Hiroshi Asanuma ◽  
Shin Ito ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Chronic Heart Failure ◽  
Kidney Disease ◽  
Diastolic Dysfunction ◽  
Uremic Toxins ◽  
Control Group ◽  
Blood Levels ◽  
Uremic Toxin ◽  
Oral Adsorbent

Background: One of uremic toxins, indoxyl sulfate (IS) is related to the progression of chronic kidney disease (CKD) and the worse cardiovascular outcomes. We have previously reported the relationship between IS levels and the severity of chronic heart failure (CHF), but the question arises as to whether the treatment of uremic toxin is beneficial in patients with CHF. This study aimed to elucidate whether the treatment with the oral adsorbent which reduces uremic toxin improved the cardiac function of the patients with CHF. Methods: First of all, we retrospectively enrolled 49 patients with both CHF and stage ≤3 CKD in our institute compared with the healthy subjects without CHF or CKD in the resident cohort study of Arita. Secondly, we retrospectively enrolled 16 CHF outpatients with stage 3-5 CKD. They were treated with and without the oral adsorbent of AST-120 for one year termed as the treatment and control groups, respectively. We underwent both blood test and echocardiography before and after the treatment. Results: First of all, among 49 patients in CHF patients, plasma IS levels increased to 1.38 ± 0.84 μg/ml from the value of 0.08 ± 0.06 μg/ml in Arita-cho as a community-living matched with gender and eGFR of CHF patients. We found both fractional shortening (FS) and E/e’, an index of diastolic function were decreased (25.0 ± 12.7%) and increased (13.7 ± 7.5), respectively in CHF patients compared with the value of FS and E/e’ in Arita-cho (FS: 41.8 ± 8.3%, E/e’: 8.8 ± 2.1). Secondly, in the treatment group, the plasma IS levels and the serum creatinine and brain natriuretic peptide levels decreased (1.40 ± 0.17 to 0.92 ± 0.15 μg/ml; p<0.05, 1.91 ± 0.16 to 1.67 ± 0.12 mg/dl; p<0.05, 352 ± 57 to 244 ± 49 pg/ml; p<0.05, respectively) and both FS and E/e’ were improved following the treatment with AST-120 (28.8 ± 2.8 to 32.9 ± 2.6%; p<0.05, 18.0 ± 2.0 to 11.8 ± 1.0; p<0.05). However, these parameters did not change in the control group. Conclusions: The treatment to decrease the blood levels of uremic toxins improved not only renal dysfunction but cardiac systolic and diastolic dysfunction in patients with chronic heart failure. Oral adsorbents might be a new treatment of heart failure especially with diastolic dysfunction.

scholarly journals ARTERIAL HYPERTENSION, CORONARY HEART DISEASE AND KIDNEY FUNCTION IN A LONG-TERM OBSERVATION

2020 ◽  
Vol 13 (6) ◽  
pp. 33-37
Author(s):  
OLGA B. OSHCHEPKOVA ◽  
◽  
EVGENY V. ARKHIPOV ◽  
GULNAZ M. MUKHAMETGALIEVA ◽  
OLGA YU. MIKHOPAROVA ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Arterial Hypertension ◽  
Kidney Function ◽  
Long Term Observation

scholarly journals Chronic Perinatal Hypoxia Delays Cardiac Maturation in a Mouse Model for Cyanotic Congenital Heart Disease

2020 ◽  
Author(s):  
Jennifer Romanowicz ◽  
Zaenab Dhari ◽  
Devon Guerrelli ◽  
Colm Mulvany ◽  
Marissa Reilly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Chronic Hypoxia ◽  
Cardiac Development ◽  
Contractile Function ◽  
Adverse Outcomes ◽  
Perinatal Hypoxia ◽  
Postnatal Environment

AbstractBackgroundCompared to acyanotic congenital heart disease (CHD), cyanotic CHD has an increased risk of lifelong mortality and morbidity. These adverse outcomes may be attributed to delayed cardiomyocyte maturation, since the transition from a hypoxic fetal milieu to oxygen rich postnatal environment is disrupted. We established a rodent model to replicate hypoxic myocardial conditions spanning perinatal development, and tested the hypothesis that chronic hypoxia impairs cardiac development.MethodsMouse dams were housed in hypoxia beginning at embryonic day 16. Pups stayed in hypoxia until postnatal day (P)8 when cardiac development is nearly complete. Global gene expression was quantified at P8 and at P30, after recovering in normoxia. Phenotypic testing included electrocardiogram, echocardiogram, and ex-vivo electrophysiology study.ResultsHypoxic animals were 48% smaller than controls. Gene expression was grossly altered by hypoxia at P8 (1427 genes affected), but normalized after recovery (P30). Electrocardiograms revealed bradycardia and slowed conduction velocity in hypoxic animals at P8, which resolved after recovery (P30). Notable differences that persisted after recovery (P30) included a 65% prolongation in ventricular effective refractory period, sinus node dysfunction, and a 24% reduction in contractile function in animals exposed to hypoxia.ConclusionsWe investigated the impact of chronic hypoxia on the developing heart. Perinatal hypoxia was associated with changes in gene expression and cardiac function. Persistent changes to the electrophysiologic substrate and contractile function warrant further investigation, and may contribute to adverse outcomes observed in the cyanotic CHD population.

A Nomogram to Predict the Probability of Relapse during Hospitalization after Minor Ischemic Stroke in Chinese Patients.

2020 ◽  
Author(s):  
Yu xianfeng ◽  
Yin wenwen ◽  
Huang chaojuan ◽  
Yuan xin ◽  
Xia yu ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Stroke ◽  
Total Bilirubin ◽  
Individual Characteristics ◽  
Adverse Outcomes ◽  
Unfavorable Outcome ◽  
Chinese Patients ◽  
Serum Total Bilirubin ◽  
Risk Of Recurrence ◽  
Minor Ischemic Stroke

Abstract Background: Predicting the risk of recurrence during hospitalization in patients with minor ischemic stroke (MIS) is of great significance for clinical and treatment. Compared with early models and prognostic scores, nomogram is a better visualization tool for predicting clinical outcomes. It combines different factors to develop a graphical continuous scoring system, and accurately calculates the risk probability of adverse outcomes based on individual characteristics. Our goal is to develop and validate a nomogram for individualized prediction of hospitalization recurrence in patients with mild ischemic stroke in the Chinese population.Methods: Based on retrospective collection, a single center study was conducted in the first affiliated Hospital of Anhui Medical University from January 2014 to December 2019. The subjects were stroke patients with NIHSS≤5.In order to generate the nomogram, age, systolic blood pressure,previous heart disease, serum total bilirubin, ferritin and smoking were integrated into the model. The predictive accuracy of the nomogram model to predict the probability of unfavorable outcome was assessed by calculation of the area under the receiver operating characteristic curve (AUC–ROC). Calibration of the risk prediction model was assessed by the plot comparing the observed probability of unfavorable outcome against the predicted, and by using the Hosmer–Lemeshow test.Results: Age at admission (OR,0.946; 95% CI,-0.002 to 0.048), SBP (OR,0.012,95%CI,0.000 to 0.024), previous heart disease (OR,0.867,95%CI, 0.084 to 1.651), UA (OR,-0.003,95%CI,-0.006 to 0.001), serum total bilirubin (OR,-0.022,95%CI,-0.036 to -0.008), ferritin (OR,0.004,95%CI, 0.002 to 0.005), smoking (OR,0.494,95%CI,-0.115 to 1.103) are significant predictors of in-hospital recurrence in Chinese patients with minor ischemic stroke.The model shows good discrimination, the AUC-ROC value is 0.737 (95%CI:0.676-0.798), and has perfect calibration performance. Calibration was good (p=0.1457 for the Hosmer-Lemesshow test), which could predict the risk of recurrence of MIS patients during hospitalization.Conclusion: The nomogram developed and validated in this study can provide individualized, intuitive and accurate prediction of recurrence in Chinese patients with minor ischemic stroke during hospitalization.

scholarly journals The Association between Gut Microbiota and Uremia of Chronic Kidney Disease

2020 ◽  
Vol 8 (6) ◽  
pp. 907 ◽  
Author(s):  
Ji Eun Kim ◽  
Hyo-Eun Kim ◽  
Ji In Park ◽  
Hyunjeong Cho ◽  
Min-Jung Kwak ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Kidney Function ◽  
Kidney Diseases ◽  
Toxin Production ◽  
Positive Interactions ◽  
Uremic Toxin ◽  
Serum Concentrations ◽  
Pyruvate Metabolism

Chronic kidney disease (CKD)-associated uremia aggravates—and is aggravated by—gut dysbiosis. However, the correlation between CKD severity and gut microbiota and/or their uremic metabolites is unclear. We enrolled 103 CKD patients with stage 1 to 5 and 46 healthy controls. We analyzed patients’ gut microbiota by MiSeq system and measured the serum concentrations of four uremic metabolites (p-cresyl sulfate, indoxyl sulfate, p-cresyl glucuronide, and trimethylamine N-oxide) by liquid chromatography–tandem mass spectrometry. Serum concentrations of the uremic metabolites increased with kidney function deterioration. Gut microbial diversity did not differ among the examined patient and control groups. In moderate or higher stage CKD groups, Oscillibacter showed positive interactions with other microbiota, and the proportions of Oscillibacter were positively correlated with those of the uremic metabolites. The gut microbiota, particularly Oscillibacter, was predicted to contribute to pyruvate metabolism which increased with CKD progression. Relative abundance of Oscillibacter was significantly associated with both serum uremic metabolite levels and kidney function. Predicted functional analysis suggested that kidney-function-associated changes in the contribution of Oscillibacter to pyruvate metabolism in CKD may greatly affect the gut environment according to kidney function, resulting in dysbiosis concomitant with uremic toxin production. The gut microbiota could be associated with uremia progression in CKD. These results may provide basis for further metagenomics analysis of kidney diseases.

scholarly journals Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chih-Huang Li ◽  
Xiaolei Tang ◽  
Samiksha Wasnik ◽  
Xiaohua Wang ◽  
Jintao Zhang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Vitamin D ◽  
Growth Factor ◽  
Kidney Failure ◽  
Mechanistic Study ◽  
Blood Levels ◽  
Biological Functions ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Fgf 23

Abstract Background Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. Methods We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. Results We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. Conclusions Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

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