Scholars@Duke
Steven Daniel Crowley

Steven Daniel Crowley

Professor of Medicine
Medicine, Nephrology
steven.d.crowley@duke.edu
Duke Box 103015, Durham, NC 27710
2nd Floor, Room 2018, MSRB II, 106 Research Drive, Durham, NC 27710

Selected Publications

Psychological Resilience and Physical Function in Veterans With Chronic Kidney Disease: A Brief Report.

Journal Article J Am Geriatr Soc · March 13, 2025 BACKGROUND: Psychological resilience has been characterized as the ability to recover from stressful life events. Not well studied is whether self-reported measures of psychological resilience are associated with physical function recovery. Therefore, we e ... Full text Link to item Cite

Transcription factor Twist1 drives fibroblast activation to promote kidney fibrosis via signaling proteins Prrx1/TNC.

Journal Article Kidney Int · November 2024 The transcription factor Twist1 plays a vital role in normal development in many tissue systems and continues to be important throughout life. However, inappropriate Twist1 activity has been associated with kidney injury and fibrosis, though the underlying ... Full text Link to item Cite

Identification of a Novel ECM Remodeling Macrophage Subset in AKI to CKD Transition by Integrative Spatial and Single-Cell Analysis.

Journal Article Adv Sci (Weinh) · October 2024 The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneit ... Full text Link to item Cite

Trajectories of Physical Resilience Among Older Veterans With Stage 4 CKD.

Journal Article Am J Kidney Dis · August 2024 RATIONALE & OBJECTIVE: Although functional impairment is common among older adults with chronic kidney disease (CKD), functional reserve before an acute health event and physical resilience after the event have not been characterized in this population. Th ... Full text Link to item Cite

Kidney Renin-Angiotensin System: Lost in a RAS Cascade.

Journal Article Hypertension · April 2024 Renin was discovered more than a century ago. Since then, the functions of the renin-angiotensin system in the kidney have been the focus of intensive research revealing its importance in regulation of renal physiology and in the pathogenesis of heart, vas ... Full text Link to item Cite

Interleukin-37: a new therapeutic target in autosomal dominant polycystic kidney disease.

Journal Article Kidney Int · April 2024 Autosomal dominant polycystic kidney disease (ADPKD) has long been considered a genetic renal disorder, but emerging evidence suggests that the immune microenvironment within the kidney plays a pivotal role in disease progression and severity. In recent ye ... Full text Link to item Cite

Swollen Feet: Considering the Paradoxical Roles of Interleukins in Nephrotic Syndrome.

Journal Article Biomedicines · March 26, 2024 Interleukins are a family of 40 bioactive peptides that act through cell surface receptors to induce a variety of intracellular responses. While interleukins are most commonly associated with destructive, pro-inflammatory signaling in cells, some also play ... Full text Link to item Cite

TNF- α from the Proximal Nephron Exacerbates Aristolochic Acid Nephropathy.

Journal Article Kidney360 · January 1, 2024 KEY POINTS: Proximal tubular TNF aggravates kidney injury and fibrogenesis in aristolochic acid nephropathy. Tubular TNF disrupts the cell cycle in injured tubular epithelial cells. TNF-mediated toxic renal injury is independent of systemic immune response ... Full text Link to item Cite

Novel anti-inflammatory effects of the IL-1 receptor in kidney myeloid cells following ischemic AKI.

Journal Article Front Mol Biosci · 2024 Introduction: Acute kidney injury (AKI) is one of the most common causes of organ failure in critically ill patients. Following AKI, the canonical pro-inflammatory cytokine interleukin-1β (IL-1β) is released predominantly from activated myeloid cells and b ... Full text Link to item Cite

Divergent Actions of Renal Tubular and Endothelial Type 1 IL-1 Receptor Signaling in Toxin-Induced AKI.

Journal Article J Am Soc Nephrol · October 1, 2023 SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney pro ... Full text Link to item Cite

Abstract P183: Porcupine Protects The Kidney By Suppressing Tubular Inflammation And Preserving Mitochondrial Integrity

Conference Hypertension · September 2023 Chronic Kidney Disease (CKD) progression may be slowed or stopped with early diagnosis and intervention, so developing novel therapies is paramount. The Wnt acyl transferase porcupine (PORCN) regulates the secretion of all 19 Wnt ligan ... Full text Cite

A macrophage-endothelial immunoregulatory axis ameliorates septic acute kidney injury.

Journal Article Kidney Int · March 2023 The most common cause of acute kidney injury (AKI) in critically ill patients is sepsis. Kidney macrophages consist of both F4/80hi and CD11bhi cells. The role of macrophage subpopulations in septic AKI pathogenesis remains unclear. As F4/80hi macrophages ... Full text Link to item Cite

Reserve and resilience in CKD: concept introduction and baseline results from the Physical REsilience Prediction in Advanced REnal Disease (PREPARED) study.

Journal Article BMC Nephrol · December 31, 2022 BACKGROUND: The purpose of this manuscript is to introduce reserve and resilience as novel concepts in chronic kidney disease (CKD) research and present baseline data from a unique prospective cohort study designed to characterize recovery from functional ... Full text Link to item Cite

Angiotensin II enhances bacterial clearance via myeloid signaling in a murine sepsis model.

Journal Article Proc Natl Acad Sci U S A · August 23, 2022 Sepsis, defined as organ dysfunction caused by a dysregulated host-response to infection, is characterized by immunosuppression. The vasopressor norepinephrine is widely used to treat low blood pressure in sepsis but exacerbates immunosuppression. An alter ... Full text Link to item Cite

Actions of Dendritic Cells in the Kidney during Hypertension.

Journal Article Compr Physiol · August 11, 2022 The immune response plays a critical role in the pathogenesis of hypertension, and immune cell populations can promote blood pressure elevation via actions in the kidney. Among these cell lineages, dendritic cells (DCs), the most potent antigen-presenting ... Full text Link to item Cite

The Immune System in Hypertension: a Lost Shaker of Salt 2021 Lewis K. Dahl Memorial Lecture.

Journal Article Hypertension · July 2022 The seminal observations of Dr Lewis Dahl regarding renal mechanisms of hypertension remain highly relevant in light of more recent experiments showing that immune system dysfunction contributes to hypertension pathogenesis. Dr Dahl established that inappr ... Full text Link to item Cite

Type 1 Angiotensin Receptors on CD11c-Expressing Cells Protect Against Hypertension by Regulating Dendritic Cell-Mediated T Cell Activation.

Journal Article Hypertension · June 2022 BACKGROUND: Type 1 angiotensin (AT1) receptors are expressed on immune cells, and we previously found that bone marrow-derived AT1 receptors protect against Ang (angiotensin) II-induced hypertension. CD11c is expressed on myeloid cells derived from the bon ... Full text Link to item Cite

IL-1 receptor signaling in podocytes limits susceptibility to glomerular damage.

Journal Article Am J Physiol Renal Physiol · February 1, 2022 Interleukin (IL)-1 receptor type 1 (IL-1R1) activation triggers a proinflammatory signaling cascade that can exacerbate kidney injury. However, the functions of podocyte IL-1R1 in glomerular disease remain unclear. To study the role of IL-1R1 signaling in ... Full text Link to item Cite

FIH-1-modulated HIF-1α C-TAD promotes acute kidney injury to chronic kidney disease progression via regulating KLF5 signaling.

Journal Article Acta Pharmacol Sin · December 2021 Incomplete recovery from episodes of acute kidney injury (AKI) can predispose patients to develop chronic kidney disease (CKD). Although hypoxia-inducible factor-1α (HIF-1α) is a master regulator of the response to hypoxia/ischemia, the role of HIF-1α in C ... Full text Link to item Cite

Polycystic kidney disease strikes a nerve.

Journal Article Physiological reports · October 2021 Full text Open Access Cite

Abstract MP31: A20 In Renal Tubular Cells Protects Against Hypertension

Conference Hypertension · September 2021 The ubiquitin-editing protein A20 suppresses NF-κB signaling, which contributes to hypertension and kidney inflammation. However, whether A20 generated directly in the kidney tubule regulates blood pressure requires elucidation. To exa ... Full text Cite

Twist1 in podocytes ameliorates podocyte injury and proteinuria by limiting CCL2-dependent macrophage infiltration.

Journal Article JCI Insight · August 9, 2021 The transcription factor Twist1 regulates several processes that could impact kidney disease progression, including epithelial cell differentiation and inflammatory cytokine induction. Podocytes are specialized epithelia that exhibit features of immune cel ... Full text Link to item Cite

Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair.

Journal Article Elife · July 19, 2021 Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, ... Full text Open Access Link to item Cite

Twist1 in T Lymphocytes Augments Kidney Fibrosis after Ureteral Obstruction.

Journal Article Kidney360 · May 27, 2021 BACKGROUND: Twist1 is a basic helix-loop-helix domain-containing transcription factor that participates in diverse cellular functions, including epithelial-mesenchymal transition and the cellular immune response. Although Twist1 plays critical roles in the ... Full text Link to item Cite

Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.

Journal Article Hypertension · February 2021 Activation of AT1 (type 1 Ang) receptors stimulates cardiomyocyte hypertrophy in vitro. Accordingly, it has been suggested that regression of cardiac hypertrophy associated with renin-Ang system blockade is due to inhibition of cellular actions of Ang II i ... Full text Link to item Cite

Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.

Conference Front Immunol · 2021 Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large inte ... Full text Link to item Cite

Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair

Journal Article · 2021 Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, ... Full text Cite

Annexin A1 Tripeptide Mimetic Increases Sirtuin-3 and Augments Mitochondrial Function to Limit Ischemic Kidney Injury.

Journal Article Front Physiol · 2021 Background: Acute kidney injury (AKI) is one of the most common organ failures following surgery. We have developed a tripeptide mimetic (ANXA1sp) of the parent annexin A1 molecule that shows promise as an organ protectant limiting cellular stress; however ... Full text Link to item Cite

Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System: Pressing Needs and Best Research Practices.

Journal Article Hypertension · November 2020 The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19-severe acute respiratory syndrome coronavi ... Full text Link to item Cite

Actions of immune cells in the hypertensive kidney.

Journal Article Curr Opin Nephrol Hypertens · September 2020 PURPOSE OF REVIEW: Inflammatory processes play a critical role in the pathogenesis of hypertension. Innate and adaptive immune responses participate in blood pressure (BP) elevation and end-organ damage. In this review, we discuss recent studies illustrati ... Full text Link to item Cite

Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI.

Journal Article Sci Adv · August 2020 Recently, extracellular vesicles (EVs) have been attracting strong research interest for use as natural drug delivery systems. We report an approach to manufacturing interleukin-10 (IL-10)-loaded EVs (IL-10+ EVs) by engineering macrophages for treating isc ... Full text Link to item Cite

Twist1: A Double-Edged Sword in Kidney Diseases.

Journal Article Kidney Dis (Basel) · July 2020 BACKGROUND: Twist1 is a basic helix-loop-helix domain containing transcription factor that regulates cell differentiation, migration, proliferation, survival, and inflammatory responses by transcriptionally regulating a wide range of downstream target gene ... Full text Link to item Cite

The varying roles of macrophages in kidney injury and repair.

Journal Article Curr Opin Nephrol Hypertens · May 2020 PURPOSE OF REVIEW: Macrophages play an important role in regulating homeostasis, kidney injury, repair, and tissue fibrogenesis. The present review will discuss recent advances that explore the novel subsets and functions of macrophage in the pathogenesis ... Full text Link to item Cite

Yolk-sac-derived macrophages progressively expand in the mouse kidney with age.

Journal Article Elife · April 17, 2020 Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, angiogenes ... Full text Link to item Cite

A complex role for Bcl10 in kidney injury.

Journal Article Cardiovasc Res · April 1, 2020 Full text Link to item Cite

Connecting cytokines and cellular signals in the nephron during CKD and hypertension.

Journal Article Kidney Int · April 2020 Chronic kidney disease features chronic inflammation and fibrosis, both of which contribute to and are exacerbated by arterial hypertension. The contribution of immune responses to renal sodium retention has received intense scrutiny. In this regard, the a ... Full text Link to item Cite

C-C Motif Chemokine Receptor 7 Exacerbates Hypertension Through Effects on T Lymphocyte Trafficking.

Journal Article Hypertension · March 2020 Activated T lymphocytes that infiltrate blood pressure control organs make a critical contribution to the pathogenesis of hypertension. Dendritic cells act as potent antigen-presenting cells to stimulate prohypertensive T cells. However, the mechanisms tha ... Full text Link to item Cite

The transcription factor Twist1 in the distal nephron but not in macrophages propagates aristolochic acid nephropathy.

Journal Article Kidney Int · January 2020 Tubulointerstitial disease in the kidney culminates in renal fibrosis that portents organ failure. Twist1, a basic helix-loop-helix protein 38 transcription factor, regulates several essential biological functions, but inappropriate Twist1 activity in the ... Full text Link to item Cite

TNF-α in T lymphocytes attenuates renal injury and fibrosis during nephrotoxic nephritis.

Journal Article Am J Physiol Renal Physiol · January 1, 2020 Nephrotoxic serum nephritis (NTN) models immune-mediated human glomerulonephritis and culminates in kidney inflammation and fibrosis, a process regulated by T lymphocytes. TNF-α is a key proinflammatory cytokine that contributes to diverse forms of renal i ... Full text Link to item Cite

Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention.

Journal Article Hypertension · January 2020 FLT3L (Fms-like tyrosine kinase 3 ligand) stimulates the development of classical dendritic cells (DCs). Here we tested the hypothesis that classical DCs drive blood pressure elevation by promoting renal fluid retention. FLT3L-deficient (FLT3L-/-) mice tha ... Full text Link to item Cite

A20 in Myeloid Cells Protects Against Hypertension by Inhibiting Dendritic Cell-Mediated T-Cell Activation.

Journal Article Circ Res · December 6, 2019 RATIONALE: The ubiquitin-editing protein A20 in dendritic cells (DCs) suppresses NF-κB (nuclear factor-κB) signaling and constrains DC-mediated T-cell stimulation, but the role of A20 in modulating the hypertensive response requires elucidation. OBJECTIVE: ... Full text Link to item Cite

Opposing actions of renal tubular- and myeloid-derived porcupine in obstruction-induced kidney fibrosis.

Journal Article Kidney Int · December 2019 Wnt/β-catenin signaling is essential in the pathogenesis of renal fibrosis. We previously reported inhibition of the Wnt O-acyl transferase porcupine, required for Wnt secretion, dramatically attenuates kidney fibrosis in the murine unilateral ureteral obs ... Full text Link to item Cite

KLF4 in Macrophages Attenuates TNFα-Mediated Kidney Injury and Fibrosis.

Journal Article J Am Soc Nephrol · October 2019 BACKGROUND: Polarized macrophage populations can orchestrate both inflammation of the kidney and tissue repair during CKD. Proinflammatory M1 macrophages initiate kidney injury, but mechanisms through which persistent M1-dependent kidney damage culminates ... Full text Link to item Cite

Twist1 in Infiltrating Macrophages Attenuates Kidney Fibrosis via Matrix Metallopeptidase 13-Mediated Matrix Degradation.

Journal Article J Am Soc Nephrol · September 2019 BACKGROUND: Following an acute insult, macrophages regulate renal fibrogenesis through the release of various factors that either encourage the synthesis of extracellular matrix synthesis or the degradation of matrix via endocytosis, proteolysis, or both. ... Full text Link to item Cite

Interleukin-1 receptor activation aggravates autosomal dominant polycystic kidney disease by modulating regulated necrosis.

Journal Article Am J Physiol Renal Physiol · August 1, 2019 Autosomal dominant polycystic kidney disease (ADPKD) is associated with increased chemokines, cytokines, and growth factors in the diseased kidney. We found that both isoforms of IL-1, IL-1α and IL-1β, were upregulated in ADPKD tissues. Here, we used a uni ... Full text Link to item Cite

Role of T-cell activation in salt-sensitive hypertension.

Journal Article Am J Physiol Heart Circ Physiol · June 1, 2019 The contributions of T lymphocytes to the pathogenesis of salt-sensitive hypertension has been well established. Under hypertensive stimuli, naive T cells develop into different subsets, including Th1, Th2, Th17, Treg, and cytotoxic CD8+ T cells, depending ... Full text Link to item Cite

Animal Models of Hypertension: A Scientific Statement From the American Heart Association.

Journal Article Hypertension · June 2019 Hypertension is the most common chronic disease in the world, yet the precise cause of elevated blood pressure often cannot be determined. Animal models have been useful for unraveling the pathogenesis of hypertension and for testing novel therapeutic stra ... Full text Link to item Cite

Stimulating Type 1 Angiotensin Receptors on T Lymphocytes Attenuates Renal Fibrosis.

Journal Article Am J Pathol · May 2019 Most forms of chronic kidney disease culminate in renal fibrosis that heralds organ failure. In contrast to the protective effects of globally blocking type 1 angiotensin (AT1) receptors throughout the body, activating AT1 receptors directly on immune cell ... Full text Link to item Cite

Corrigendum

Journal Article American Journal of Physiology-Renal Physiology · May 1, 2019 Full text Cite

Dynamic contrast-enhanced MRI promotes early detection of toxin-induced acute kidney injury.

Journal Article Am J Physiol Renal Physiol · February 1, 2019 Acute kidney injury (AKI) is a common cause of morbidity and mortality in hospitalized patients. Nevertheless, there is limited ability to diagnose AKI in its earliest stages through the collection of structural and functional information. Magnetic resonan ... Full text Link to item Cite

HIF-1α inducing exosomal microRNA-23a expression mediates the cross-talk between tubular epithelial cells and macrophages in tubulointerstitial inflammation.

Journal Article Kidney Int · February 2019 Hypoxia promotes tubulointerstitial inflammation in the kidney. Although hypoxia inducible factor-1α (HIF-1α) is a master regulator of the response to hypoxia, the exact mechanisms through which HIF-1α modulates the induction of tubulointerstitial inflamma ... Full text Link to item Cite

Employing Macrophage-Derived Microvesicle for Kidney-Targeted Delivery of Dexamethasone: An Efficient Therapeutic Strategy against Renal Inflammation and Fibrosis.

Journal Article Theranostics · 2019 Although glucocorticoids are the mainstays in the treatment of renal diseases for decades, the dose dependent side effects have largely restricted their clinical use. Microvesicles (MVs) are small lipid-based membrane-bound particles generated by virtually ... Full text Link to item Cite

Renal Effects of Cytokines in Hypertension.

Journal Article Adv Exp Med Biol · 2019 Preclinical studies point to a key role for immune cells in hypertension via augmenting renal injury and/or hypertensive responses. Blood pressure elevation in rheumatologic patients is attenuated by anti-inflammatory therapies. Both the innate and adaptiv ... Full text Link to item Cite

Drebrin regulates angiotensin II-induced aortic remodelling.

Journal Article Cardiovasc Res · November 1, 2018 AIMS: The actin-binding protein Drebrin is up-regulated in response to arterial injury and reduces smooth muscle cell (SMC) migration and proliferation through its interaction with the actin cytoskeleton. We, therefore, tested the hypothesis that SMC Drebr ... Full text Open Access Link to item Cite

Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy.

Journal Article Am J Pathol · November 2018 IgA nephropathy (IgAN) features variable renal pathology and a heterogeneous clinical course. Our aim was to search noninvasive biomarkers from urinary exosomes for IgAN patients; membrane nephropathy and minimal change disease were included as other glome ... Full text Link to item Cite

ATAC-ing the mechanisms of renin regulation.

Journal Article J Clin Invest · November 1, 2018 Renin-expressing cells have been conserved through evolution and maintain blood pressure and fluid homeostasis. Lack of availability of tools to study the specifics of renin regulation has limited advances in this field. In the current issue of the Journal ... Full text Link to item Cite

Inflammation in Salt-Sensitive Hypertension and Renal Damage.

Journal Article Curr Hypertens Rep · October 30, 2018 PURPOSE OF REVIEW: Low-grade inflammation drives elevations in blood pressure (BP) and consequent target organ damage in diverse experimental models of hypertension. Here, we discuss recent advances elucidating immune-mediated mechanisms of BP elevation an ... Full text Link to item Cite

Interleukin 1 receptor (IL-1R1) activation exacerbates toxin-induced acute kidney injury.

Journal Article Am J Physiol Renal Physiol · September 1, 2018 Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Drug-induced/toxic AKI can be caused by a number of therapeutic agents. Cisplatin is an effective chemotherapeutic agent whose administration is limited by significant nephrotoxicity. ... Full text Link to item Cite

Hydroxychloroquine attenuates renal ischemia/reperfusion injury by inhibiting cathepsin mediated NLRP3 inflammasome activation.

Journal Article Cell Death Dis · March 2, 2018 Inflammation is a major contributor to the pathogenesis of ischemic acute kidney injury (AKI), which complicates the post-operative outcomes of large numbers of hospitalized surgical patients. Hydroxychloroquine (HCQ), a well-known anti-malarial drug, is c ... Full text Link to item Cite

Renal effects of cytokines in hypertension.

Journal Article Curr Opin Nephrol Hypertens · March 2018 PURPOSE OF REVIEW: Inflammatory cytokines contribute to the pathogenesis of hypertension through effects on renal blood flow and sodium handling. This review will update recent advances that explore the renal actions of immune cells and cytokines in the pa ... Full text Link to item Cite

Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial Inflammation.

Journal Article J Am Soc Nephrol · March 2018 Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released f ... Full text Link to item Cite

Salt, Hypertension, and Immunity.

Journal Article Annu Rev Physiol · February 10, 2018 The link between inappropriate salt retention in the kidney and hypertension is well recognized. However, growing evidence suggests that the immune system can play surprising roles in sodium homeostasis, such that the study of inflammatory cells and their ... Full text Link to item Cite

A novel role for renal epithelial cells and the medullary sodium gradient in the local immune response.

Journal Article Kidney Int · December 2017 The extreme hypertonicity of the renal medulla plays a central role in regulating volume status. A recent publication in Cell has identified a novel role for the high sodium environment and the local epithelial cells in the recruitment of mononuclear phago ... Full text Link to item Cite

Immunologic Effects of the Renin-Angiotensin System.

Journal Article J Am Soc Nephrol · May 2017 Inappropriate activation of the renin-angiotensin system (RAS) exacerbates renal and vascular injury. Accordingly, treatment with global RAS antagonists attenuates cardiovascular risk and slows the progression of proteinuric kidney disease. By reducing BP, ... Full text Open Access Link to item Cite

The role of chemokines in hypertension and consequent target organ damage.

Journal Article Pharmacol Res · May 2017 Immune cells infiltrate the kidney, vasculature, and central nervous system during hypertension, consequently amplifying tissue damage and/or blood pressure elevation. Mononuclear cell motility depends partly on chemokines, which are small cytokines that g ... Full text Open Access Link to item Cite

The role of macrophages in hypertension and its complications.

Journal Article Pflugers Arch · April 2017 Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension, a highly prevalent disease associated with catastrophic cardiovascular morbidity. In the vasculature and kidney, macrophage-derived reactive oxygen species ... Full text Open Access Link to item Cite

Elevated PTH induces endothelial-to-chondrogenic transition in aortic endothelial cells.

Journal Article Am J Physiol Renal Physiol · March 1, 2017 Previous studies have shown that increased parathyroid hormone (PTH) attributable to secondary hyperparathyroidism in chronic kidney disease accelerates the arteriosclerotic fibrosis and calcification. Although the underlying mechanisms remain largely unkn ... Full text Open Access Link to item Cite

Characterization and Functional Phenotyping of Renal Immune Cells via Flow Cytometry.

Journal Article Methods Mol Biol · 2017 A variety of immune cell subsets contribute to the pathogenesis of hypertension and associated kidney damage following inappropriate activation of the renin-angiotensin system (RAS). These immune cell subsets often express common surface markers, which com ... Full text Link to item Cite

Targeting cytokine signaling in salt-sensitive hypertension.

Journal Article Am J Physiol Renal Physiol · December 1, 2016 Activated immune cell populations contribute to hypertension in part through inciting damage to the kidney and by provoking inappropriate sodium reabsorption in the nephron. Inflammatory mediators called cytokines produced by T lymphocytes and macrophages ... Full text Open Access Link to item Cite

C-C Motif Chemokine 5 Attenuates Angiotensin II-Dependent Kidney Injury by Limiting Renal Macrophage Infiltration.

Journal Article Am J Pathol · November 2016 Inappropriate activation of the renin angiotensin system (RAS) is a key contributor to the pathogenesis of essential hypertension. During RAS activation, infiltration of immune cells into the kidney exacerbates hypertension and renal injury. However, the m ... Full text Open Access Link to item Cite

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI.

Journal Article J Am Soc Nephrol · August 2016 Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulatin ... Full text Open Access Link to item Cite

Experimental inhibition of porcupine-mediated Wnt O-acylation attenuates kidney fibrosis.

Journal Article Kidney Int · May 2016 Activated Wnt signaling is critical in the pathogenesis of renal fibrosis, a final common pathway for most forms of chronic kidney disease. Therapeutic intervention by inhibition of individual Wnts or downstream Wnt/β-catenin signaling has been proposed, b ... Full text Open Access Link to item Cite

Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron.

Journal Article Cell Metab · February 9, 2016 Hypertension is among the most prevalent and catastrophic chronic diseases worldwide. While the efficacy of renin angiotensin system (RAS) blockade in lowering blood pressure illustrates that the RAS is broadly activated in human hypertension, the frequent ... Full text Link to item Cite

Megalin/Cubulin-Lysosome-mediated Albumin Reabsorption Is Involved in the Tubular Cell Activation of NLRP3 Inflammasome and Tubulointerstitial Inflammation.

Journal Article J Biol Chem · July 17, 2015 Albuminuria contributes to the development and progression of chronic kidney disease by inducing tubulointerstitial inflammation (TI) and fibrosis. However, the exact mechanisms of TI in response to albuminuria are unresolved. We previously demonstrated th ... Full text Link to item Cite

Role of T lymphocytes in hypertension.

Journal Article Curr Opin Pharmacol · April 2015 Accumulating evidence indicates that the immune system plays a critical role in the pathogenesis of cardiovascular diseases including hypertension. Mice lacking T lymphocytes are resistant to blood pressure elevation, suggesting a key contribution of T lym ... Full text Link to item Cite

Tumor necrosis factor-α produced in the kidney contributes to angiotensin II-dependent hypertension.

Journal Article Hypertension · December 2014 Immune system activation contributes to the pathogenesis of hypertension and the resulting progression of chronic kidney disease. In this regard, we recently identified a role for proinflammatory Th1 T-lymphocyte responses in hypertensive kidney injury. Be ... Full text Link to item Cite

Activation of the Nlrp3 inflammasome by mitochondrial reactive oxygen species: a novel mechanism of albumin-induced tubulointerstitial inflammation.

Journal Article Int J Biochem Cell Biol · December 2014 Albuminuria is not only an important marker of chronic kidney disease but also a crucial contributor to tubulointerstitial inflammation (TIF). In this study, we determined whether activation of the Nlrp3 inflammasome is involved in albuminuria induced-TIF ... Full text Link to item Cite

Classical Renin-Angiotensin system in kidney physiology.

Journal Article Compr Physiol · July 2014 The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardiovascular system and the central nervous system. Along with its impact o ... Full text Link to item Cite

The inextricable role of the kidney in hypertension.

Journal Article J Clin Invest · June 2014 Featured Publication An essential link between the kidney and blood pressure control has long been known. Here, we review evidence supporting the premise that an impaired capacity of the kidney to excrete sodium in response to elevated blood pressure is a major contributor to ... Full text Link to item Cite

Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis.

Journal Article J Clin Invest · May 2014 Featured Publication In a wide array of kidney diseases, type 1 angiotensin (AT1) receptors are present on the immune cells that infiltrate the renal interstitium. Here, we examined the actions of AT1 receptors on macrophages in progressive renal fibrosis and found that macrop ... Full text Link to item Cite

Endothelial cell autoantibodies in predicting declining renal function, end-stage renal disease, or death in adult type 2 diabetic nephropathy

Journal Article Frontiers in Endocrinology · January 1, 2014 Albuminuria is a strong predictor of diabetic nephropathy chronic kidney disease outcomes. Yet, therapeutic albuminuria-lowering has not consistently translated into a reduction in clinical events suggesting the involvement of additional pathogenic factors ... Full text Cite

The cooperative roles of inflammation and oxidative stress in the pathogenesis of hypertension.

Journal Article Antioxid Redox Signal · January 1, 2014 Featured Publication SIGNIFICANCE: Innate and adaptive immunity play fundamental roles in the development of hypertension and its complications. As effectors of the cell-mediated immune response, myeloid cells and T lymphocytes protect the host organism from infection by attac ... Full text Link to item Cite

The Renin-Angiotensin System

Journal Article · September 12, 2013 Full text Cite

The role of type 1 angiotensin receptors on T lymphocytes in cardiovascular and renal diseases.

Journal Article Curr Hypertens Rep · February 2013 The renin-angiotensin system plays a critical role in the pathogenesis of several cardiovascular diseases, largely through activation of type I angiotensin (AT(1)) receptors by angiotensin II. Treatment with AT(1) receptor blockers (ARBs) is a proven succe ... Full text Link to item Cite

The Renin-Angiotensin System

Chapter · December 31, 2012 Full text Cite

Taking a sound approach to acute kidney injury.

Journal Article Am J Physiol Renal Physiol · December 1, 2012 Full text Link to item Cite

A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension.

Journal Article Circ Res · June 8, 2012 Featured Publication RATIONALE: Human clinical trials using type 1 angiotensin (AT(1)) receptor antagonists indicate that angiotensin II is a critical mediator of cardiovascular and renal disease. However, recent studies have suggested that individual tissue pools of AT(1) rec ... Full text Link to item Cite

Recent advances involving the renin-angiotensin system.

Journal Article Exp Cell Res · May 15, 2012 The renin-angiotensin system (RAS) exercises fundamental control over sodium and water handling in the kidney. Accordingly, dysregulation of the RAS leads to blood pressure elevation with ensuing renal and cardiovascular damage. Recent studies have reveale ... Full text Link to item Cite

Prehypertension and chronic kidney disease: the ox or the plow?

Journal Article Kidney Int · February 2012 Nearly ten years ago, practice recommendations supported use of the clinical classification of 'prehypertension' for people with systolic blood pressure of 120-139 mm Hg or diastolic pressure of 80-89 mm Hg. This recommendation was based on observations th ... Full text Link to item Cite

Role of AT₁ receptor-mediated salt retention in angiotensin II-dependent hypertension.

Journal Article Am J Physiol Renal Physiol · November 2011 Activation of type 1 angiotensin II (AT(1)) receptors in the kidney promotes blood pressure elevation and target organ damage, but whether renal AT(1) receptors influence the level of hypertension by stimulating sodium retention or by raising systemic vasc ... Full text Link to item Cite

Gene expression profiles linked to AT1 angiotensin receptors in the kidney.

Journal Article Physiol Genomics · November 15, 2010 To characterize gene expression networks linked to AT(1) angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT(1A) receptor-deficient mice (KOs) at baseline and after 2 days of ... Full text Link to item Cite

Lymphocyte responses exacerbate angiotensin II-dependent hypertension.

Journal Article Am J Physiol Regul Integr Comp Physiol · April 2010 Featured Publication Activation of the immune system by ANG II contributes to the pathogenesis of hypertension, and pharmacological suppression of lymphocyte responses can ameliorate hypertensive end-organ damage. Therefore, to examine the mechanisms through which lymphocytes ... Full text Link to item Cite

A role for angiotensin II type 1 receptors on bone marrow-derived cells in the pathogenesis of angiotensin II-dependent hypertension.

Journal Article Hypertension · January 2010 Featured Publication Activation of type 1 angiotensin (AT(1)) receptors causes hypertension, leading to progressive kidney injury. AT(1) receptors are expressed on immune cells, and previous studies have identified a role for immune cells in angiotensin II-dependent hypertensi ... Full text Link to item Cite

Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis.

Journal Article J Clin Invest · April 2009 Featured Publication Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we genera ... Full text Link to item Cite

The Renin-Angiotensin System

Journal Article · December 1, 2008 Full text Cite

In hypertension, the kidney breaks your heart.

Journal Article Curr Cardiol Rep · November 2008 The renin-angiotensin system (RAS) is a master regulator of blood pressure and fluid homeostasis. Because RAS components are expressed in several tissues that may influence blood pressure, studies using conventional gene targeting to globally interrupt the ... Full text Link to item Cite

Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension.

Journal Article Am J Physiol Renal Physiol · August 2008 Featured Publication Activation of the renin-angiotensin system contributes to the progression of chronic kidney disease. Based on the known cellular effects of ANG II to promote inflammation, we posited that stimulation of lymphocyte responses by ANG II might contribute to th ... Full text Link to item Cite

Kidney in hypertension: guyton redux.

Journal Article Hypertension · April 2008 Full text Link to item Cite

In hypertension, the kidney rules.

Journal Article Curr Hypertens Rep · April 2007 Featured Publication The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Components of the RAS, including renin, angiotensin-converting enzyme (ACE), and angiotensin type 1 (AT1) receptors, are expressed throughout the body in ti ... Full text Link to item Cite

AT(1) receptors and control of blood pressure: the kidney and more..

Journal Article Trends Cardiovasc Med · January 2007 The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. The components of the RAS including renin, angiotensin-converting enzyme, and angiotensin receptors are expressed throughout the body in tissues that may im ... Full text Link to item Cite

Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney.

Journal Article Proc Natl Acad Sci U S A · November 21, 2006 Featured Publication Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenge ... Full text Link to item Cite

Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system.

Journal Article J Clin Invest · April 2005 Featured Publication Angiotensin II, acting through type 1 angiotensin (AT(1)) receptors, has potent effects that alter renal excretory mechanisms. Control of sodium excretion by the kidney has been suggested to be the critical mechanism for blood pressure regulation by the re ... Full text Link to item Cite

Exploring type I angiotensin (AT1) receptor functions through gene targeting.

Journal Article Acta Physiol Scand · August 2004 The renin-angiotensin system (RAS) modulates a diverse set of physiological processes including development, blood pressure, renal function and inflammation. The principal effector molecule of this system, angiotensin II, mediates most of these actions. Th ... Full text Link to item Cite

Effector mechanisms in transplant rejection.

Journal Article Immunol Rev · December 2003 Antigens, provided by the allograft, trigger the activation and proliferation of allospecific T cells. As a consequence of this response, effector elements are generated that mediate graft injury and are responsible for the clinical manifestations of allog ... Full text Link to item Cite

Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells.

Journal Article J Immunol · July 1, 2003 Coordinated rearrangements of the actin-myosin cytoskeleton facilitate early and late events in T cell activation and signal transduction. As many important features of cell shape rearrangement involve small GTP-binding proteins, we examined the contributi ... Full text Link to item Cite

A Web-based compendium of clinical questions and medical evidence to educate internal medicine residents.

Journal Article Acad Med · March 2003 Featured Publication The authors designed an electronic database of clinical questions (CQs) and medical evidence and implemented it in 2001-02 at Duke University Medical Center and the Veterans Administration Medical Center in Durham, North Carolina. This Web-based data colle ... Full text Link to item Cite

Coronary steal from a left internal mammary artery coronary bypass graft by a left upper extremity arteriovenous hemodialysis fistula.

Journal Article Am J Kidney Dis · October 2002 In patients with end-stage renal disease undergoing hemodialysis, the upper extremity arteriovenous (AV) fistula is the dialysis access recommended by the DOQI guidelines for patients with appropriate vasculature. Upper extremity AV fistulae have long peri ... Full text Link to item Cite

Immunological properties of bacterial DNA.

Journal Article Annals of the New York Academy of Sciences · November 1995 Full text Cite