Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2.

The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension.

Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1.

Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence.

Serum Activity Against G Protein-Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome.

Background Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein-coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell-based assay.

Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome.

Background: Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology.

Methods: We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283).

Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1β Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension.

Background And Objectives: Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via IL-1β activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, HIF-1α gene expression from whole blood and urine samples and IL-1βgene expression from whole blood were measured.

Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease.

Background: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested.

Methods: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study.

Proconvertase Furin Is Downregulated in Postural Orthostatic Tachycardia Syndrome.

Postural Orthostatic Tachycardia Syndrome (POTS) is a cardiovascular autonomic disorder characterized by orthostatic intolerance and high prevalence among young women. The etiology of POTS is uncertain, though autoimmunity and inflammation may play an important role. We aimed to identify novel inflammatory biomarkers associated with POTS.

Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease.

Introduction: Loss of renal function is associated with high mortality from cardiovascular disease (CVD). Patients with chronic kidney disease (CKD) have altered circulating adipokine and nonesterified fatty acid concentrations and insulin resistance, which are features of disturbed adipose tissue metabolism. Because dysfunctional adipose tissue contributes to the development of CVD, we hypothesize that adipose tissue dysfunctionality in patients with CKD could explain, at least in part, their high rates of CVD.

Proximal Tubular Expression Patterns of Megalin and Cubilin in Proteinuric Nephropathies.

Introduction: Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubules. For albumin this process involves at least 2 interacting receptors, megalin and cubilin. Albumin is not usually present in the urine, indicating a highly efficient tubular reuptake under physiological conditions.

The FGF23-Klotho axis and cardiac tissue Doppler imaging in pediatric chronic kidney disease-a prospective cohort study.

Background: Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD.

Methods: This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.

Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Currently, overt hypertension and increased renal volume are the best predictors of renal function. In this study, we assessed the usefulness of selected circulating microRNAs (miRs) to predict disease progress in a cohort with ADPKD.

Differential hemoglobin A sequestration between hemodialysis modalities.

This report evaluates plasma protein patterns, dialysates and protein analysis of used dialysis membranes from the same patient under hemodialysis in three separate modalities, using high-flux membranes in concentration-driven transport (HD), convection-driven hemofiltration (HF) and combined hemodialfiltration (HDF). The plasma protein changes induced by each of the three dialysis modalities showed small differences in proteins identified towards our previous plasma analyses of chronic kidney disease (CKD) patients. The used dialysate peptide concentrations likewise exhibited small differences among the modalities and varied in the same relative order as the plasma changes, with protein losses in the order HD>HDF>HF.

Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown.

Vasopressin-related copeptin is a novel predictor of early endothelial dysfunction in patients with adult polycystic kidney disease.

Background: In this study, we examined the relative usefulness of serum copeptin levels as a surrogate marker of vasopressin (AVP) in adult polycystic kidney disease (ADPKD) by correlating it with baseline and longitudinal changes in markers of both renal function and common CVD manifestations (hypertensive vascular disease, atherosclerosis and endothelial dysfunction) that accompany the progression of this disease.

Methods: We studied a cohort of young and otherwise healthy ADPKD patients (n = 235) and measured cardiovascular function using flow-mediation dilatation (FMD), carotid intima media thickness (cIMT) and pulse wave velocity (PWV), as well as serum copeptin (commercial ELISA, a stable marker of AVP activity). The same analyses were carried out at baseline and after 3 years of follow-up.

Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD.

Background And Objectives: The high risk of cardiovascular disease (CVD) and premature death in patients with CKD associates with a plethora of elevated circulating biomarkers that may reflect distinct signaling pathways or simply, are epiphenomena of CKD. We compared the predictive strength of 12 biomarkers analyzed concomitantly in patients with stage 5 CKD.

Design, Setting, Participants, & Measurements: From 1994 to 2014, 543 patients with stage 5 CKD (median age =56 years old; 63% men; 199 patients had CVD) took part in our study on malnutrition, inflammation, and CVD in incident dialysis patients.

Changes in gluconeogenesis and intracellular lipid accumulation characterize uremic human hepatocytes ex vivo.

It is well known that reduced glomerular filtration rate (GFR) leads to an increased risk of dyslipidemia, insulin resistance, and cardiovascular mortality. The liver is a central organ for metabolism, but its function in the uremic setting is still poorly characterized. We used human primary hepatocytes isolated from livers of nine donors with normal renal function to investigate perturbations in key metabolic pathways following exposure to uremic (n = 8) or healthy (n = 8) sera, and to serum-free control medium.

Assessing longitudinal trends in cardiac function among pediatric patients with chronic kidney disease.

Background: Left ventricular diastolic dysfunction (LVDD) is an early marker of cardiac disease in pediatric chronic kidney disease (CKD), but few studies have analyzed longitudinal trends. We conducted a prospective 3-year follow-up study in pediatric CKD and kidney transplant (CKD-T) patients.

Methods: The patient cohort comprised 30 CKD and 42 CKD-T patients.

Complementary LC-MS/MS Proteomic Analysis of Uremic Plasma Proteins.

Objective: To complement an earlier analysis of protein alterations in plasma from uremic versus healthy subjects by addition of further LC-MS/MS analysis to the previously used MALDI-TOF mass analyses.

Methodology: Sequence identifications of tryptic peptides from SDS gel electrophoretic fractions of immunodepleted and HPLC-fractionated plasma was performed from seven chronic kidney disease stage 5 patients (age 55 ± 14 years, glomerular filtration rate 6.9 ±2.

In vitro affinity reduction of biologic response modifiers from production buffy coat platelets exposed to recombinant protein receptors.

Background: Recent studies link biologic response modifiers found in donor platelet (PLT) concentrates to transfusion reactions. We tested a novel method to deplete BRMs from PLT concentrates using apheresis.

Study Design And Methods: Whole blood from 25 donors was treated to yield PLTs for in vitro measurements on Days 2, 5, and 7.

Selection of genetic and phenotypic features associated with inflammatory status of patients on dialysis using relaxed linear separability method.

Identification of risk factors in patients with a particular disease can be analyzed in clinical data sets by using feature selection procedures of pattern recognition and data mining methods. The applicability of the relaxed linear separability (RLS) method of feature subset selection was checked for high-dimensional and mixed type (genetic and phenotypic) clinical data of patients with end-stage renal disease. The RLS method allowed for substantial reduction of the dimensionality through omitting redundant features while maintaining the linear separability of data sets of patients with high and low levels of an inflammatory biomarker.

Impaired postprandial fibroblast growth factor (FGF)-19 response in patients with stage 5 chronic kidney diseases is ameliorated following antioxidative therapy.

Background: While dysmetabolism is common in patients with chronic kidney disease (CKD) and associated with mortality, the mechanisms mediating these changes are unclear. New data implicate fibroblast growth factor (FGF)-19 as a possible entero-hepatic modulator of lipid metabolism.

Methods: Using samples previously gathered as part of a randomized placebo-controlled study of antioxidative therapy for postprandial dysmetabolism, we investigated short-term (4 h) postprandial changes in circulating FGF-19 (ELISA) and the relationship to metabolic markers in six haemodialysis (HD) patients and nine matched healthy subjects (HS), with each participant assessed on four separate occasions.

Serum hepatocyte growth factor is associated with truncal fat mass and increased mortality in chronic kidney disease stage 5 patients with protein-energy wasting.

Background: Obese sarcopenia characterized by increased fat mass and protein-energy wasting (PEW) is not uncommon in chronic kidney disease (CKD) stage 5 patients in whom it is associated with worse outcomes. Serum hepatocyte growth factor (HGF) is associated with obesity in the general population and is increased in CKD patients in whom its association with body composition is not known. We studied the associations between HGF, PEW and body composition, and between HGF and mortality, in CKD stage 5 patients starting dialysis.

Serum uric acid levels and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease.

Background/aims: Patients with autosomal dominant polycystic kidney disease (ADPKD) exhibit endothelial dysfunction (ED) despite normal levels of renal function. Hyperuricemia occurs in these patients and has been postulated to affect ED through the generation of oxidative stress. We therefore investigated the prevalence of ED and its association with serum uric acid levels in early-stage ADPKD.

Left ventricular diastolic dysfunction by tissue Doppler echocardiography in pediatric chronic kidney disease.

Background: Myocardial dysfunction is common in chronic kidney disease (CKD) and related to poor outcomes. New non-invasive methods to assess cardiac function have been introduced, but comparative studies evaluating their clinical usefulness in pediatric CKD are lacking. We studied left ventricular (LV) function in pediatric CKD and renal transplant patients, comparing conventional pulse-wave Doppler echocardiography (cPWD) with newer tissue Doppler imaging (TDI) and relating the results to known cardiovascular risk factors.

Differences in acute metabolism of fructose between hemodialysis patients and healthy subjects.

The consumption of fructose has increased dramatically during the last few decades and parallels the epidemics of obesity, metabolic syndrome, diabetes and chronic kidney disease (CKD). Fructose occurs naturally e.g.