TMAO reductase, a biomarker for gut permeability defect induced inflammation, in mouse model of chronic kidney disease and dextran sulfate solution-induced mucositis.

BACKGROUND: The excretion of trimethylamine N-oxide (TMAO) (uremic toxin) into the intestine might be enhanced, due to the limited renal elimination in chronic kidney disease (CKD), possibly induced TMAO reductase (a TMAO-neutralizing enzyme) in gut bacteria. Detection of TMAO reductase in serum could be used as a biomarker of gut permeability defect. OBJECTIVE: To explore the correlation between serum TMAO reductase, gut leakage, and systemic inflammation in CKD. METHODS: Mouse models of gut leakage; including 5/6 nephrectomy-induced chronic kidney disease (CKD), a model without colitis, and 1.5% dextran sulfate solution (DSS), a colitis model, were performed. In parallel, serum samples from patients with chronic hemodialysis (n = 48) and the healthy control (n = 20) were analyzed. RESULTS: Gut-leakage (FITC-dextran, endotoxemia, and reduced intestinal tight junction protein) was detected in both CKD and DSS models. While TMAO reductase and TMAO were elevated in the serum of both mouse models and patients, TMAO reductase correlated with TMAO, gut- leakage, and serum IL-6 only in mice but not in patients. Notably, endotoxemia was used as a surrogate marker of gut leakage in patients. In patients, TMAO reductase and TMAO did not correlate with serum IL-6 and vascular complications using the ankle-brachial index and cardio-ankle vascular index. CONCLUSIONS: Serum TMAO reductase was elevated in CKD mice and patients with CKD. Serum TMAO reductase was correlated with TMAO and gut-leakage only in mice but not in patients. Further studies in patients are needed to determine the benefit of serum TMAO reductase in patients with CKD.

3D Intracardiac Echocardiography in Mitral Transcatheter Edge-to-Edge Repair: When TEE Is Hard to Stomach.

Intracardiac echocardiography (ICE) has historically had limited utility in complex structural interventions. Newer 3-dimensional ICE catheters have enhanced imaging and real-time functionality. We present a novel case of mitral valve transcatheter edge-to-edge repair where transesophageal imaging was limited by massive hiatal hernia and where complementary 3D ICE imaging enabled procedural success. (Level of Difficulty: Intermediate.).

Association Between Indoxyl Sulfate and Dialysis Initiation and Cardiac Outcomes in Chronic Kidney Disease Patients.

Introduction: Indoxyl sulfate, a protein-bound uremic toxin, has been reported as an atherosclerosis and fibrosis accelerator. This study aimed to determine whether serum indoxyl sulfate is associated with cardiac abnormalities, cardiovascular events, and renal progression to dialysis in patients with chronic kidney disease (CKD). Methods: The prospective study enrolled 89 patients with CKD stage 3 to 5 patients. Serum biochemistry data and indoxyl sulfate were measured. All patients underwent echocardiographic examination. Global longitudinal strain (GLS) was calculated using two-dimensional speckle tracking. The clinical outcomes including cardiovascular event and dialysis initiation were recorded during a 2-year follow-up. Results: Patients were divided into 2 groups based on the median value of serum indoxyl sulfate (low and high indoxyl sulfate groups). Kaplan-Meier analysis revealed that patients with higher indoxyl sulfate (≥6.124 mg/L) were significantly associated with renal progression to dialysis (p < 0.001). There was no significant difference in cardiovascular events between 2 groups (p = 0.082). In addition, serum indoxyl sulfate level was independently associated with GLS (r = 0.62; p = 0.01). The risk of cardiovascular events was significantly higher in patients with impaired GLS (>-16%) (p = 0.015). Conclusion: Serum indoxyl sulfate level was a significant predictor for CKD progression to dialysis and was correlated with GLS, a speckle tracking echocardiography parameter representing early LV systolic dysfunction. Furthermore, GLS was associated with cardiovascular events in CKD patients. Serum indoxyl sulfate measurement may help to identify the high dialysis and cardiovascular risk CKD patients beyond traditional risk factors.

Idiopathic pericardial effusion in patients with hypertrophic cardiomyopathy.

The aims of this study were to examine the prevalence of moderate to large (moderate-large) idiopathic pericardial effusion (i-PEF) in patients with hypertrophic cardiomyopathy (HCM) and to identify clinical and echocardiographic hemodynamic profiles associated with pericardial effusion. A total of 292 adult patients with HCM were studied. Fifteen patients with a history of factors associated with pericardial effusion including myocardial infarction, heart surgery or cardiac procedure within the last 12 months, autoimmune disease, hydralazine use, chronic kidney disease stage 3-4, tuberculosis, and malignancy were excluded. Of 277 eligible patients with HCM, 11 patients (4%) with moderate-large i-PEF were identified. Clinical tamponade was present in 1 patient. Compared to patients with HCM who had no or small pericardial effusion, patients with moderate-large i-PEF were younger and more likely to have right ventricular (RV) hypertrophy and reverse septal curvature. These patients also exhibited a greater maximal septal thickness, mean and systolic pulmonary pressure, and right atrial pressure (p < 0.05 for all). Pericardial fluid analysis and histopathological exams were performed in 7 and 3 patients, respectively. All examinations revealed transudative and nonspecific etiology of pericardial effusion. Idiopathic pericardial effusion and cardiac tamponade in patients with HCM was uncommon. The pathophysiology involved in pericardial effusion remains undetermined. Patients with moderate-large i-PEF frequently exhibited a phenotype of pulmonary hypertension and RV pressure overload.

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial.

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups -5.61 mg/L; 95% CI -11.01 to -0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.

Non-Vitamin K Antagonist Oral Anticoagulants Provide Less Adverse Renal Outcomes Than Warfarin In Non-Valvular Atrial Fibrillation: A Systematic Review and MetaAnalysis.

Background Non-vitamin K antagonist oral anticoagulants (NOACs) have better pharmacologic properties than warfarin and are recommended in preference to warfarin in most patients with non-valvular atrial fibrillation. Besides lower bleeding complications, other advantages of NOACs over warfarin particularly renal outcomes remain inconclusive. Methods and Results Electronic searches were conducted through Medline, Scopus, Cochrane Library databases, and ClinicalTrial.gov. Randomized controlled trials and observational cohort studies reporting incidence rates and hazard ratio (HR) of renal outcomes (including acute kidney injury, worsening renal function, doubling serum creatinine, and end-stage renal disease) were selected. The random-effects model was used to calculate pooled incidence and HR with 95% CI. Eighteen studies were included. A total of 285 201 patients were enrolled, 118 863 patients with warfarin and 166 338 patients with NOACs. The NOACs group yielded lower incidence rates of all renal outcomes when compared with the warfarin group. Patients treated with NOACs showed significantly lower HR of risk of acute kidney injury (HR, 0.70, 95% CI, 0.64-0.76; P<0.001), worsening renal function (HR, 0.83; 95% CI, 0.73-0.95; P=0.006), doubling serum creatinine (HR, 0.58; 95% CI, 0.41-0.82; P=0.002), and end-stage renal disease (HR, 0.82; 95% CI, 0.78-0.86; P<0.001). Conclusions In non-valvular atrial fibrillation, patients treated with NOACs have a lower risk of both acute kidney injury and end-stage renal disease when compared with warfarin.

Echocardiographic Findings Among Virally Suppressed HIV-Infected Aging Asians Compared with HIV-Negative Individuals.

OBJECTIVES: Prevalence of cardiovascular disease increases with age. Little is known about the prevalence and risk factors for echocardiographic abnormalities among older people living with HIV (PLHIV) from Asia. DESIGN: A cross-sectional study was conducted among PLHIV aged >50 years (N = 298) on antiretroviral treatment (ART) and HIV-negative controls (N = 100) frequency matched by sex and age in Thailand. METHODS: All participants underwent standard 2-dimensional transthoracic echocardiography performed by trained cardiologists who were blinded to the participant's care and HIV status. Logistic regression was used to examine the association between cardiac abnormalities and risk factors. RESULTS: The median age was 54.7 years (60.8% men) with 37.2% having hypertension and 16.6% having diabetes mellitus. PLHIV was on ART for a median of 16.2 years with current CD4 cell counts of 616 cells per cubic millimeter. Echocardiogram abnormalities did not differ among PLHIV (55%) and the controls (60%). The major abnormalities in PLHIV were following: left ventricular (LV) hypertrophy: 37% men and 42.2% women, LV systolic dysfunction (0.7%), diastolic dysfunction (24.2%), and pulmonary hypertension (3.9%). From the multivariate analyses in PLHIV, being aged >60 years was independently associated with diastolic dysfunction, whereas female sex and left atrial volume index of >34 mL/m were associated with pulmonary hypertension (P < 0.05). None of the ART was significantly associated with any major echocardiographic abnormalities. CONCLUSIONS: In this long-term, well-suppressed, older, Asian PLHIV cohort, the prevalence of asymptomatic LV systolic dysfunction and pulmonary hypertension were relatively low, whereas the diastolic dysfunction and LV hypertrophy were common. Echocardiographic findings did not differ between PLHIV and HIV-uninfected controls.

Current practice of diagnosis and management of acute kidney injury in intensive care unit in resource limited settings.

PURPOSE: In a resource limited settings, there is sparse information about the management of acute kidney injury (AKI) based on systemic data collection. This survey aimed to described the current management of AKI in intensive care units (ICUs) across Thailand. MATERIALS AND METHODS: Questionnaires were distributed to 160 physicians involved in the intensive care between January and December 2014 across Thailand. Distribution was done through an online survey platform or telephone interview. RESULTS: The response rate was 80.6% (129 physicians). AKI diagnosis was mostly made by using KDIGO criteria (36.7%). A common diagnostic investigation of AKI was urinalysis (86%). Nephrologists had a major role (86.4%) in deciding the initiation and selection of renal replacement therapy (RRT) modality. Intermittent hemodialysis is the preferable mode of RRT (72.0%), followed by continuous renal replacement therapy (CRRT, 12%), sustained low efficiency dialysis (10.0%) and peritoneal dialysis (6.0%). Catheter insertion was predominantly performed by nephrologist (51.1%) with ultrasound guidance. The right internal jugular vein was the most common site of insertion (70.4%). The most common indication for CRRT was hemodynamic instability. CONCLUSIONS: Amid increasing concern of AKI in the ICU, our study provides the insight into the management of AKI in resource limited settings.