-
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 -
Nature Reviews. Nephrology Oct 2017The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive... (Review)
Review
The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these important functions and can adapt to different metabolic conditions through a number of signalling pathways (for example, mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways) that activate the transcriptional co-activator peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and by balancing mitochondrial dynamics and energetics to maintain mitochondrial homeostasis. Mitochondrial dysfunction leads to a decrease in ATP production, alterations in cellular functions and structure, and the loss of renal function. Persistent mitochondrial dysfunction has a role in the early stages and progression of renal diseases, such as acute kidney injury (AKI) and diabetic nephropathy, as it disrupts mitochondrial homeostasis and thus normal kidney function. Improving mitochondrial homeostasis and function has the potential to restore renal function, and administering compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus. Furthermore, inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.
Topics: Animals; Disease Progression; Homeostasis; Humans; Kidney; Kidney Diseases; Mitochondria; Mitochondrial Diseases; Signal Transduction
PubMed: 28804120
DOI: 10.1038/nrneph.2017.107 -
Advances in Chronic Kidney Disease Jan 2016Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The... (Review)
Review
Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.
Topics: Aged; Aged, 80 and over; Aging; Glomerular Filtration Rate; Humans; Kidney; Renal Insufficiency
PubMed: 26709059
DOI: 10.1053/j.ackd.2015.08.004 -
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 -
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 -
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 -
The Journal of Clinical Endocrinology... Oct 2014Asymptomatic primary hyperparathyroidism (PHPT) is routinely encountered in clinical practices of endocrinology throughout the world. This report distills an update of...
OBJECTIVE
Asymptomatic primary hyperparathyroidism (PHPT) is routinely encountered in clinical practices of endocrinology throughout the world. This report distills an update of current information about diagnostics, clinical features, and management of this disease into a set of revised guidelines.
PARTICIPANTS
Participants, representing an international constituency, with interest and expertise in various facets of asymptomatic PHPT constituted four Workshop Panels that developed key questions to be addressed. They then convened in an open 3-day conference September 19-21, 2013, in Florence, Italy, when a series of presentations and discussions addressed these questions. A smaller subcommittee, the Expert Panel, then met in closed session to reach an evidence-based consensus on how to address the questions and data that were aired in the open forum.
EVIDENCE
Preceding the conference, each question was addressed by a relevant, extensive literature search. All presentations and deliberations of the Workshop Panels and the Expert Panel were based upon the latest information gleaned from this literature search.
CONSENSUS PROCESS
The expert panel considered all the evidence provided by the individual Workshop Panels and then came to consensus.
CONCLUSION
In view of new findings since the last International Workshop on the Management of Asymptomatic PHPT, guidelines for management have been revised. The revised guidelines include: 1) recommendations for more extensive evaluation of the skeletal and renal systems; 2) skeletal and/or renal involvement as determined by further evaluation to become part of the guidelines for surgery; and 3) more specific guidelines for monitoring those who do not meet guidelines for parathyroid surgery. These guidelines should help endocrinologists and surgeons caring for patients with PHPT. A blueprint for future research is proposed to foster additional investigation into issues that remain uncertain or controversial.
Topics: Asymptomatic Diseases; Education; Endocrinology; Evidence-Based Medicine; Humans; Hyperparathyroidism, Primary; Practice Guidelines as Topic
PubMed: 25162665
DOI: 10.1210/jc.2014-1413 -
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