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British Journal of Hospital Medicine... May 2022Hypertension is a leading risk factor for cardiovascular disease and all-cause mortality globally. Hypertension and chronic kidney disease are closely intertwined... (Review)
Review
Hypertension is a leading risk factor for cardiovascular disease and all-cause mortality globally. Hypertension and chronic kidney disease are closely intertwined conditions as hypertension can lead to deteriorating renal function and progressive chronic kidney disease can contribute to worsening hypertension. In the setting of chronic kidney disease, the pathophysiology of hypertension is complex and involves the interplay of many factors including a reduced number of functioning nephrons, sodium retention and volume expansion, upregulation of the sympathetic nervous system, hormonal factors such as upregulation of the renin-angiotensin-aldosterone system, and endothelial dysfunction. Poorly controlled hypertension can accelerate the progression to end-stage kidney disease. This review discusses the pathophysiological mechanisms that contribute to hypertension, including sympathetic nervous system activity, the renin-angiotensin-aldosterone system and the role of sodium. In the setting of chronic kidney disease, the relationship with hypertension and renovascular disease as a potential cause and target for therapeutic intervention is briefly reviewed. Finally, treatment options, targets and the long-term cardiovascular benefits of optimal blood pressure control are discussed.
Topics: Humans; Hypertension; Kidney; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sodium
PubMed: 35653320
DOI: 10.12968/hmed.2021.0440 -
Annual Review of Physiology Feb 2021Renal sympathetic (efferent) nerves play an important role in the regulation of renal function, including glomerular filtration, sodium reabsorption, and renin release.... (Review)
Review
Renal sympathetic (efferent) nerves play an important role in the regulation of renal function, including glomerular filtration, sodium reabsorption, and renin release. The kidney is also innervated by sensory (afferent) nerves that relay information to the brain to modulate sympathetic outflow. Hypertension and other cardiometabolic diseases are linked to overactivity of renal sympathetic and sensory nerves, but our mechanistic understanding of these relationships is limited. Clinical trials of catheter-based renal nerve ablation to treat hypertension have yielded promising results. Therefore, a greater understanding of how renal nerves control the kidney under physiological and pathophysiological conditions is needed. In this review, we provide an overview of the current knowledge of the anatomy of efferent and afferent renal nerves and their functions in normal and pathophysiological conditions. We also suggest further avenues of research for development of novel therapies targeting the renal nerves.
Topics: Afferent Pathways; Animals; Catheter Ablation; Humans; Hypertension; Kidney
PubMed: 33566672
DOI: 10.1146/annurev-physiol-031620-091656 -
Nutrients May 2021Potassium (K), the main cation inside cells, plays roles in maintaining cellular osmolarity and acid-base equilibrium, as well as nerve stimulation transmission, and... (Review)
Review
Potassium (K), the main cation inside cells, plays roles in maintaining cellular osmolarity and acid-base equilibrium, as well as nerve stimulation transmission, and regulation of cardiac and muscle functions. It has also recently been shown that K has an antihypertensive effect by promoting sodium excretion, while it is also attracting attention as an important component that can suppress hypertension associated with excessive sodium intake. Since most ingested K is excreted through the kidneys, decreased renal function is a major factor in increased serum levels, and target values for its intake according to the degree of renal dysfunction have been established. In older individuals with impaired renal function, not only hyperkalemia but also hypokalemia due to anorexia, K loss by dialysis, and effects of various drugs are likely to develop. Thus, it is necessary to pay attention to K management tailored to individual conditions. Since abnormalities in K metabolism can also cause lethal arrhythmia or sudden cardiac death, it is extremely important to monitor patients with a high risk of hyper- or hypokalemia and attempt to provide early and appropriate intervention.
Topics: Adult; Aged; Blood Pressure; Female; Humans; Hyperkalemia; Hypokalemia; Kidney; Male; Middle Aged; Nutritional Status; Potassium; Recommended Dietary Allowances; Renal Insufficiency, Chronic
PubMed: 34063969
DOI: 10.3390/nu13061751 -
Nefrologia 2020Cell death is a finely regulated process occurring through different pathways. Regulated cell death, either through apoptosis or regulated necrosis offers the... (Review)
Review
Cell death is a finely regulated process occurring through different pathways. Regulated cell death, either through apoptosis or regulated necrosis offers the possibility of therapeutic intervention. Necroptosis and ferroptosis are among the best studied forms of regulated necrosis in the context of kidney disease. We now review the current evidence supporting a role for ferroptosis in kidney disease and the implications of this knowledge for the design of novel therapeutic strategies. Ferroptosis is defined functionally, as a cell modality characterized by peroxidation of certain lipids, constitutively suppressed by GPX4 and inhibited by iron chelators and lipophilic antioxidants. There is functional evidence of the involvement of ferroptosis in diverse forms of kidneys disease. In a well characterized nephrotoxic acute kidney injury model, ferroptosis caused an initial wave of death, triggering an inflammatory response that in turn promoted necroptotic cell death that perpetuated kidney dysfunction. This suggests that ferroptosis inhibitors may be explored as prophylactic agents in clinical nephrotoxicity or ischemia-reperfusion injury such as during kidney transplantation. Transplantation offers the unique opportunity of using anti-ferroptosis agent ex vivo, thus avoiding bioavailability and in vivo pharmacokinetics and pharmacodynamics issues.
Topics: Ferroptosis; Humans; Kidney Diseases
PubMed: 32624210
DOI: 10.1016/j.nefro.2020.03.005 -
Circulation Research Apr 2023Arterial and venous thrombosis constitute a major source of morbidity and mortality worldwide. Association between thrombotic complications and cardiovascular and other... (Review)
Review
Arterial and venous thrombosis constitute a major source of morbidity and mortality worldwide. Association between thrombotic complications and cardiovascular and other chronic inflammatory diseases are well described. Inflammation and subsequent initiation of thrombotic events, termed immunothrombosis, also receive growing attention but are still incompletely understood. Nevertheless, the clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is evident by an increased risk of thrombosis and cardiovascular events in patients with inflammatory or infectious diseases. Proinflammatory mediators released from platelets, complement activation, and the formation of NETs (neutrophil extracellular traps) initiate and foster immunothrombosis. In this review, we highlight and discuss prominent and emerging interrelationships and functions between NETs and other mediators in immunothrombosis in cardiovascular disease. Also, with patients with chronic kidney disease suffering from increased cardiovascular and thrombotic risk, we summarize current knowledge on neutrophil phenotype, function, and NET formation in chronic kidney disease. In addition, we elaborate on therapeutic targeting of NETs-induced immunothrombosis. A better understanding of the functional relevance of antithrombotic mediators which do not increase bleeding risk may provide opportunities for successful therapeutic interventions to reduce thrombotic risk beyond current treatment options.
Topics: Humans; Extracellular Traps; Thrombosis; Inflammation; Thromboinflammation; Neutrophils; Renal Insufficiency, Chronic
PubMed: 37053273
DOI: 10.1161/CIRCRESAHA.123.321750 -
American Journal of Physiology. Renal... Dec 2020
Topics: Blood Pressure; Databases, Bibliographic; Humans; Hypertension; Information Dissemination; Internet; Kidney; Kidney Diseases; Periodicals as Topic; Physiology; United States
PubMed: 33166184
DOI: 10.1152/ajprenal.00572.2020 -
Diabetes Care Jan 2023The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the... (Review)
Review
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Topics: Humans; Standard of Care; Diabetes Mellitus; Renal Insufficiency, Chronic; Societies, Medical; Reference Standards; Endocrinology
PubMed: 36507634
DOI: 10.2337/dc23-S011 -
Cell Death & Disease Sep 2019Acute kidney injury (AKI) is a syndrome of abrupt loss of renal functions. The underlying pathological mechanisms of AKI remain largely unknown. BCL2-interacting protein...
Acute kidney injury (AKI) is a syndrome of abrupt loss of renal functions. The underlying pathological mechanisms of AKI remain largely unknown. BCL2-interacting protein 3 (BNIP3) has dual functions of regulating cell death and mitophagy, but its pathophysiological role in AKI remains unclear. Here, we demonstrated an increase of BNIP3 expression in cultured renal proximal tubular epithelial cells following oxygen-glucose deprivation-reperfusion (OGD-R) and in renal tubules after renal ischemia-reperfusion (IR)-induced injury in mice. Functionally, silencing Bnip3 by specific short hairpin RNAs in cultured renal tubular cells reduced OGD-R-induced mitophagy, and potentiated OGD-R-induced cell death. In vivo, Bnip3 knockout worsened renal IR injury, as manifested by more severe renal dysfunction and tissue injury. We further showed that Bnip3 knockout reduced mitophagy, which resulted in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and enhanced cell death and inflammatory response in kidneys following renal IR. Taken together, these findings suggest that BNIP3-mediated mitophagy has a critical role in mitochondrial quality control and tubular cell survival during AKI.
Topics: Acute Kidney Injury; Animals; Apoptosis; Kidney; Kidney Tubules; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Mitophagy; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction
PubMed: 31515472
DOI: 10.1038/s41419-019-1899-0 -
Physiological Reviews Jan 2024Aging is a chronic yet natural physiological decline of the body. Throughout life, humans are continuously exposed to a variety of exogenous and endogenous stresses,... (Review)
Review
Aging is a chronic yet natural physiological decline of the body. Throughout life, humans are continuously exposed to a variety of exogenous and endogenous stresses, which engender various counteractive responses at the cellular, tissue, organ, as well as organismal levels. The compromised cellular and tissue functions that occur because of genetic factors or prolonged stress (or even the stress response) may accelerate aging. Over the last two decades, the sirtuin (SIRT) family of lysine deacylases has emerged as a key regulator of longevity in a variety of organisms. SIRT7, the most recently identified member of the SIRTs, maintains physiological homeostasis and provides protection against aging by functioning as a watchdog of genomic integrity, a dynamic sensor and modulator of stresses. SIRT7 decline disrupts metabolic homeostasis, accelerates aging, and increases the risk of age-related pathologies including cardiovascular and neurodegenerative diseases, pulmonary and renal disorders, inflammatory diseases, and cancer, etc. Here, we present SIRT7 as the seventh key to unlock the mystery of aging, and its specific manipulation holds great potential to ensure healthiness and longevity.
Topics: Humans; Aging; Sirtuins
PubMed: 37676263
DOI: 10.1152/physrev.00044.2022 -
Cell Metabolism Mar 2024The glucagon receptor (GCGR) in the kidney is expressed in nephron tubules. In humans and animal models with chronic kidney disease, renal GCGR expression is reduced....
The glucagon receptor (GCGR) in the kidney is expressed in nephron tubules. In humans and animal models with chronic kidney disease, renal GCGR expression is reduced. However, the role of kidney GCGR in normal renal function and in disease development has not been addressed. Here, we examined its role by analyzing mice with constitutive or conditional kidney-specific loss of the Gcgr. Adult renal Gcgr knockout mice exhibit metabolic dysregulation and a functional impairment of the kidneys. These mice exhibit hyperaminoacidemia associated with reduced kidney glucose output, oxidative stress, enhanced inflammasome activity, and excess lipid accumulation in the kidney. Upon a lipid challenge, they display maladaptive responses with acute hypertriglyceridemia and chronic proinflammatory and profibrotic activation. In aged mice, kidney Gcgr ablation elicits widespread renal deposition of collagen and fibronectin, indicative of fibrosis. Taken together, our findings demonstrate an essential role of the renal GCGR in normal kidney metabolic and homeostatic functions. Importantly, mice deficient for kidney Gcgr recapitulate some of the key pathophysiological features of chronic kidney disease.
Topics: Humans; Animals; Mice; Receptors, Glucagon; Down-Regulation; Mice, Knockout; Kidney; Renal Insufficiency, Chronic; Homeostasis; Lipids
PubMed: 38237602
DOI: 10.1016/j.cmet.2023.12.024