Christopher S. Wilcox
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View article: The Paradox of Hypertonic Saline Infusion for Patients with Heart Failure
The Paradox of Hypertonic Saline Infusion for Patients with Heart Failure Open
Background: Fluid/sodium overload is the primary reason for hospital admission for patients with acute decompensated heart failure. Unfortunately, congestion often remains undertreated and is associated with significant adverse outcomes in…
View article: Potassium Dysregulation in Patients with CKD
Potassium Dysregulation in Patients with CKD Open
Hyperkalemia has long been the focus of potassium (K + ) dysregulation in patients with CKD. However, although the risks of hyperkalemia are well known and clearly important, there is growing evidence that hypokalemia occurs at least as fr…
View article: Examining Symptom Management and Quality of Life of Loop Diuretic-Induced Overactive Bladder Among Heart Failure Patients: Physician and Patient Perspectives
Examining Symptom Management and Quality of Life of Loop Diuretic-Induced Overactive Bladder Among Heart Failure Patients: Physician and Patient Perspectives Open
Loop diuretics are strongly recommended in patients with chronic congestive heart failure (HF) to alleviate signs and symptoms of fluid overload. Loop diuretics help relieve congestive symptoms and reduce mortality, but may have side effec…
View article: Bladder Symptoms Provoked by Short, Rapid-Acting Loop Diuretics: A Frequent but Often Overlooked Problem
Bladder Symptoms Provoked by Short, Rapid-Acting Loop Diuretics: A Frequent but Often Overlooked Problem Open
BACKGROUND Bladder dysfunction entails overactive bladder (OAB) defined as symptoms of urinary urgency, frequency, and/or nocturia with or without incontinence if there is no obvious pathology or infection or lower urinary tract symptoms t…
View article: Effects of Sotagliflozin on Health Status in Patients With Worsening Heart Failure
Effects of Sotagliflozin on Health Status in Patients With Worsening Heart Failure Open
Sotagliflozin improved symptoms, physical limitations, and quality of life within 4 months after worsening HF, with consistent benefits across baseline demographic and clinical characteristics. (Effect of Sotagliflozin on Cardiovascular Ev…
View article: Methods for the Assessment of Volume Overload and Congestion in Heart Failure
Methods for the Assessment of Volume Overload and Congestion in Heart Failure Open
Acute decompensated heart failure entails a dysregulation of renal and cardiac function, with fluid volume excess or congestion being a key component. We provide an overview of methods for its assessment in clinical practice. Evaluation of…
View article: Signals From Inflamed Perivascular Adipose Tissue Contribute to Small-Vessel Dysfunction in Women With Human Immunodeficiency Virus
Signals From Inflamed Perivascular Adipose Tissue Contribute to Small-Vessel Dysfunction in Women With Human Immunodeficiency Virus Open
Background People with the human immunodeficiency virus (PWH) have microvascular disease. Because perivascular adipose tissue (PVAT) regulates microvascular function and adipose tissue is inflamed in PWH, we tested the hypothesis that PWH …
View article: Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects
Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects Open
Significance Statement The effect of sodium–glucose cotransporter-2 inhibitors (SGLT2i) on regional tubular sodium handling is poorly understood in humans. In this study, empagliflozin substantially decreased lithium reabsorption in the pr…
View article: Effect of Sotagliflozin on Early Mortality and Heart Failure-Related Events
Effect of Sotagliflozin on Early Mortality and Heart Failure-Related Events Open
Starting sotagliflozin before discharge in patients with type 2 diabetes hospitalized for WHF significantly decreased cardiovascular deaths and HF events through 30 and 90 days after discharge, emphasizing the importance of beginning sodiu…
View article: Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes
Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes Open
SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in the early proximal renal tubule, but the magnitude and duration of any ensuing natriuretic or diuretic effect are the result of an i…
View article: A kidney-brain neural circuit drives progressive kidney damage and heart failure
A kidney-brain neural circuit drives progressive kidney damage and heart failure Open
Chronic kidney disease (CKD) and heart failure (HF) are highly prevalent, aggravate each other, and account for substantial mortality. However, the mechanisms underlying cardiorenal interaction and the role of kidney afferent nerves and th…
View article: Corrigendum to Cao W, Shi M, Wu L, et al. “A renal-cerebral-peripheral sympathetic reflex mediates insulin resistance in chronic kidney disease” EBioMedicine. 2018 Nov;37:281–293
Corrigendum to Cao W, Shi M, Wu L, et al. “A renal-cerebral-peripheral sympathetic reflex mediates insulin resistance in chronic kidney disease” EBioMedicine. 2018 Nov;37:281–293 Open
In the above-stated article, the authors inadvertently placed a duplicated image of angiotensin II staining in SFO for the 5/6Nx+HS Epi RTX group in Fig. 4a. This unfortunate mistake was made during the final assembly of the images from di…
View article: Activation of Nrf2 in Mice Causes Early Microvascular Cyclooxygenase-Dependent Oxidative Stress and Enhanced Contractility
Activation of Nrf2 in Mice Causes Early Microvascular Cyclooxygenase-Dependent Oxidative Stress and Enhanced Contractility Open
Nuclear factor erythroid factor E2-related factor 2 (Nrf2) transcribes antioxidant genes that reduce the blood pressure (BP), yet its activation with tert-butylhydroquinone (tBHQ) in mice infused with angiotensin II (Ang II) increased mean…
View article: Development and Validation of Prediction Models for Hypertensive Nephropathy, the PANDORA Study
Development and Validation of Prediction Models for Hypertensive Nephropathy, the PANDORA Study Open
Importance Hypertension is a leading cause of end-stage renal disease (ESRD), but currently, those at risk are poorly identified. Objective To develop and validate a prediction model for the development of hypertensive nephropathy (HN). De…
View article: Low Dose Chronic Angiotensin II Induces Selective Senescence of Kidney Endothelial Cells
Low Dose Chronic Angiotensin II Induces Selective Senescence of Kidney Endothelial Cells Open
Angiotensin II can cause oxidative stress and increased blood pressure that result in long term cardiovascular pathologies. Here we evaluated the contribution of cellular senescence to the effect of chronic exposure to low dose angiotensin…
View article: Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure
Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure Open
Aims In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to…
View article: Renal negative pressure treatment as a novel therapy for heart failure-induced renal dysfunction
Renal negative pressure treatment as a novel therapy for heart failure-induced renal dysfunction Open
Congestion is the primary pathophysiological lesion in most heart failure (HF) hospitalizations. Renal congestion increases renal tubular pressure, reducing glomerular filtration rate (GFR) and diuresis. Because each nephron is a fluid-fil…
View article: Diuretic Resistance Treated with Low-Dose Hydralazine: A Case Report and Review of the Literature
Diuretic Resistance Treated with Low-Dose Hydralazine: A Case Report and Review of the Literature Open
We present a case of severe diuretic resistance and edema from acute cardiorenal syndrome complicating heart failure with preserved ejection fraction (HFpEF) and mild alcoholic liver disease. High doses of intravenous (iv) furosemide plus …
View article: Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure
Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure Open
Sanofi at initiation and Lexicon Pharmaceuticals at completion.
View article: When Off Target Effects Are On Target: The Role Of Spironolactone In Patients With COVID-19
When Off Target Effects Are On Target: The Role Of Spironolactone In Patients With COVID-19 Open
Aims: Spironolactone is a steroidal mineralocoricosteroid receptor antagonist (MRA) used for treatment of resistant hypertension, heart failure and edema. It exerts class specific adverse effects that are shared by other MRAs. Additionally…
View article: Pathophysiology of Hypertension
Pathophysiology of Hypertension Open
Dr Irvine Page proposed the Mosaic Theory of Hypertension in the 1940s advocating that hypertension is the result of many factors that interact to raise blood pressure and cause end-organ damage. Over the years, Dr Page modified his paradi…
View article: Is Spironolactone the Preferred Renin–Angiotensin–Aldosterone Inhibitor for Protection Against COVID-19?
Is Spironolactone the Preferred Renin–Angiotensin–Aldosterone Inhibitor for Protection Against COVID-19? Open
The high mortality of specific groups from COVID-19 highlights the importance of host–viral interactions and the potential benefits from enhancing host defenses. SARS-CoV-2 requires angiotensin-converting enzyme (ACE) 2 as a receptor for c…
View article: Long-Term Predialysis Systolic Blood Pressure Variability and Intradialytic Cardiac Hemodynamics in Hemodialysis Patients
Long-Term Predialysis Systolic Blood Pressure Variability and Intradialytic Cardiac Hemodynamics in Hemodialysis Patients Open
The association in hemodialysis patients between long-term predialysis blood pressure variability and intradialytic cardiac hemodynamics was assessed prospectively in 1070 patients receiving maintenance hemodialysis for more than 3 months.…
View article: Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure
Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure Open
In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and …
View article: Acute Kidney Injury Sensitizes the Brain Vasculature to Ang II (Angiotensin II) Constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1)
Acute Kidney Injury Sensitizes the Brain Vasculature to Ang II (Angiotensin II) Constriction via FGFBP1 (Fibroblast Growth Factor Binding Protein 1) Open
Acute kidney injury (AKI) causes multiple organ dysfunction. Here, we identify a possible mechanism that can drive brain vessel injury after AKI. We induced 30-minute bilateral renal ischemia-reperfusion injury in C57Bl/6 mice and isolated…
View article: Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure
Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure Open
Diuretic resistance implies a failure to increase fluid and sodium (Na + ) output sufficiently to relieve volume overload, edema, or congestion, despite escalating doses of a loop diuretic to a ceiling level (80 mg of furosemide once or tw…
View article: Sympathetic Overactivity in CKD Disrupts Buffering of Neurotransmission by Endothelium-Derived Hyperpolarizing Factor and Enhances Vasoconstriction
Sympathetic Overactivity in CKD Disrupts Buffering of Neurotransmission by Endothelium-Derived Hyperpolarizing Factor and Enhances Vasoconstriction Open
Significance Statement Vascular smooth muscle cells (VSMCs) of resistance arteries receive sympathetic nerve signals, and subsequently elicit an endothelium-dependent anticontractile response to modulate vasoconstriction, but the specific …
View article: Renal Nerve Deafferentation Attenuates the Fall in GFR during Intravenous Infusion of Furosemide in Anesthetized Rats
Renal Nerve Deafferentation Attenuates the Fall in GFR during Intravenous Infusion of Furosemide in Anesthetized Rats Open
Introduction: Furosemide reduces the glomerular filtration rate (GFR) and increases the renal vascular resistance (RVR) despite inhibiting tubuloglomerular feedback but increases proximal tubule pressure, renin release, and renal nerve act…
View article: NaHCO <sub>3</sub> Dilates Mouse Afferent Arteriole Via Na <sup>+</sup> /HCO <sub>3</sub> <sup>−</sup> Cotransporters NBCs
NaHCO <sub>3</sub> Dilates Mouse Afferent Arteriole Via Na <sup>+</sup> /HCO <sub>3</sub> <sup>−</sup> Cotransporters NBCs Open
Sodium bicarbonate has long been used to treat chronic kidney disease. It has been demonstrated to slow the decline in glomerular filtration rate in chronic kidney disease patient; however, the mechanisms are not completely understood. We …
View article: Endothelin-1-Induced Microvascular ROS and Contractility in Angiotensin-II-Infused Mice Depend on COX and TP Receptors
Endothelin-1-Induced Microvascular ROS and Contractility in Angiotensin-II-Infused Mice Depend on COX and TP Receptors Open
(1) Background: Angiotensin II (Ang II) and endothelin 1 (ET-1) generate reactive oxygen species (ROS) that can activate cyclooxygenase (COX). However, thromboxane prostanoid receptors (TPRs) are required to increase systemic markers of RO…