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American Journal of Physiology. Renal... Jun 2019Afferent arteriole (Af-Art) diameter regulates pressure and flow into the glomerulus, which are the main determinants of the glomerular filtration rate. Thus, Af-Art... (Review)
Review
Afferent arteriole (Af-Art) diameter regulates pressure and flow into the glomerulus, which are the main determinants of the glomerular filtration rate. Thus, Af-Art resistance is crucial for Na filtration. Af-Arts play a role as integrative centers, where systemic and local systems interact to determine the final degree of resistance. The tubule of a single nephron contacts an Af-Art of the same nephron at two locations: in the transition of the thick ascending limb to the distal tubule (macula densa) and again in the connecting tubule. These two sites are the anatomic basis of two intrinsic feedback mechanisms: tubule-glomerular feedback and connecting tubule-glomerular feedback. The cross communications between the tubules and Af-Arts integrate tubular Na and water processing with the hemodynamic conditions of the kidneys. Tubule-glomerular feedback provides negative feedback that tends to avoid salt loss, and connecting tubule-glomerular feedback provides positive feedback that favors salt excretion by modulating tubule-glomerular feedback (resetting it) and increasing glomerular filtration rate. These feedback mechanisms are also exposed to systemic modulators (hormones and the nervous system); however, they can work in isolated kidneys or nephrons. The exaggerated activation or absence of any of these mechanisms may lead to disequilibrium in salt and water homeostasis, especially in extreme conditions (e.g., high-salt diet/low-salt diet) and may be part of the pathogenesis of some diseases. In this review, we focus on molecular signaling, feedback interactions, and the physiological roles of these two feedback mechanisms.
Topics: Animals; Epithelial Sodium Channels; Feedback, Physiological; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney Glomerulus; Kidney Tubules; Renal Circulation; Sodium; Water-Electrolyte Balance; Water-Electrolyte Imbalance
PubMed: 30838873
DOI: 10.1152/ajprenal.00381.2018 -
Clinical and Experimental Pharmacology... Feb 2017Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and... (Review)
Review
Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented.
Topics: Acute Kidney Injury; Animals; Autonomic Nervous System; Humans; Kidney; Kidney Function Tests; Microcirculation; Renal Circulation; Vagus Nerve Stimulation
PubMed: 28116780
DOI: 10.1111/1440-1681.12694 -
Critical Care (London, England) Mar 2018The importance of personalized blood pressure management is well recognized. Because renal pressure-flow relationships may vary among patients, understanding how renal... (Review)
Review
The importance of personalized blood pressure management is well recognized. Because renal pressure-flow relationships may vary among patients, understanding how renal autoregulation may influence blood pressure control is essential. However, much remains uncertain regarding the determinants of renal autoregulation in circulatory shock, including the influence of comorbidities and the effects of vasopressor treatment. We review published studies on renal autoregulation relevant to the management of acutely ill patients with shock. We delineate the main signaling pathways of renal autoregulation, discuss how it can be assessed, and describe the renal autoregulatory alterations associated with chronic disease and with shock.
Topics: Animals; Blood Pressure; Disease Models, Animal; Dogs; Homeostasis; Kidney; Mice; Renal Circulation; Shock; Swine; Vasoconstrictor Agents
PubMed: 29566705
DOI: 10.1186/s13054-018-1962-8 -
General Thoracic and Cardiovascular... Jan 2019It is indisputable that open thoracoabdominal aortic aneurysm (TAAA) repair remains a highly complex and sophisticated surgical intervention. Despite advancements in the... (Review)
Review
It is indisputable that open thoracoabdominal aortic aneurysm (TAAA) repair remains a highly complex and sophisticated surgical intervention. Despite advancements in the imaging modality, evolution of our understanding of the pathology afflicting the aorta, intraoperative brain and spinal cord monitoring, intraoperative organ protection, postoperative critical care and organ support, monitoring and the close follow-up of affected patients, this type of surgery remains a challenge to the surgeon and the patient. In this review, we will illustrate the recent evidence on renal protection and prediction during TAAA.
Topics: Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Humans; Kidney; Kidney Diseases; Renal Circulation; Retrospective Studies; Treatment Outcome
PubMed: 28956257
DOI: 10.1007/s11748-017-0835-4 -
Kidney360 May 2021This review outlines the available data from the work of our group on renal hemodynamics, function, and oxygenation in patients who are critically ill with acute renal... (Review)
Review
This review outlines the available data from the work of our group on renal hemodynamics, function, and oxygenation in patients who are critically ill with acute renal dysfunction, such as those with postoperative AKI, those in early clinical septic shock, in patients undergoing cardiac surgery with cardiopulmonary bypass, or in patients undergoing liver transplantation. We also provide information on renal hemodynamics, function, and oxygenation in patients with chronic renal impairment due to congestive heart failure. This review will argue that, for all of these groups of patients, the common denominator is that renal oxygenation is impaired due to a lower renal oxygen delivery or a pronounced increase in renal oxygen consumption.
Topics: Critical Illness; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney; Renal Circulation
PubMed: 35373068
DOI: 10.34067/KID.0007012020 -
Current Opinion in Critical Care Dec 2020This review discusses the macrocirculatory and microcirculatory aspects of renal perfusion, as well as novel methods by which to measure renal blood flow. Finally,... (Review)
Review
PURPOSE OF REVIEW
This review discusses the macrocirculatory and microcirculatory aspects of renal perfusion, as well as novel methods by which to measure renal blood flow. Finally, therapeutic options are briefly discussed, including renal-specific microcirculatory effects.
RECENT FINDINGS
The optimal mean arterial pressure (MAP) needed for preservation of renal function has been debated but is most likely a MAP of 60-80 mmHg. In addition, attention should be paid to renal outflow pressure, typically central venous pressure. Heterogeneity in microcirculation can exist and may be mitigated through appropriate use of vasopressors with unique microcirculatory effects. Excessive catecholamines have been shown to be harmful and should be avoided. Both angiotensin II and vasopressin may improve glomerular flow through a number of mechanisms. Macrocirculatory and microcirculatory blood flow can be measured through a number of bedside ultrasound modalities, sublingual microscopy and urinary oxygen measurement, SUMMARY: Acute kidney injury (AKI) is a common manifestation of organ failure in shock, and avoidance of hemodynamic instability can mitigate this risk. Measurement of renal haemodynamics is not routinely performed but may help to guide therapeutic goals. A thorough understanding of pathophysiology, measurement techniques and therapeutic options may allow for a personalized approach to blood pressure management in patients with septic shock and may ultimately mitigate AKI.
Topics: Hemodynamics; Humans; Microcirculation; Renal Circulation; Shock, Septic; Vasoconstrictor Agents
PubMed: 33044238
DOI: 10.1097/MCC.0000000000000774 -
British Journal of Anaesthesia Sep 2020
Topics: Betacoronavirus; Brain Diseases; COVID-19; Coronavirus Infections; Humans; Lung Diseases; Myocarditis; Pandemics; Pneumonia, Viral; Renal Circulation; SARS-CoV-2; Thromboembolism
PubMed: 32731958
DOI: 10.1016/j.bja.2020.06.013 -
The American Journal of Cardiology Dec 2019Sodium-glucose co-transporter 2 (SGLT2) inhibitors immediately reduce the glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus. When given... (Review)
Review
Sodium-glucose co-transporter 2 (SGLT2) inhibitors immediately reduce the glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus. When given chronically, they confer benefit by markedly slowing the rate at which chronic kidney disease progresses and are the first agents to do so since the advent of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Salutary effects on the kidney were first demonstrated in cardiovascular outcomes trials and have now emerged from trials enriched in subjects with type 2 diabetes mellitus and chronic kidney disease. A simple model that unifies the immediate and long-term effects of SGLT2 inhibitors on kidney function is based on the assumption that diabetic hyperfiltration puts the kidney at long-term risk and evidence that hyperfiltration is an immediate response to a reduced signal for tubuloglomerular feedback, which occurs to the extent that SGLT2 activity mediates a primary increase in sodium and fluid reabsorption by the proximal tubule. This model will likely continue to serve as a useful description accounting for the beneficial effect of SGLT2 inhibitors on the diabetic kidney, similar to the hemodynamic explanation for the benefit of ACEIs and ARBs. A more complex model will be required to incorporate positive interactions between SGLT2 and sodium-hydrogen exchanger 3 in the proximal tubule and between sodium-glucose co-transporter 1 (SGLT1) and nitric oxide synthase in the macula densa. The implication of these latter nuances for day-to-day clinical medicine remains to be determined.
Topics: Diabetes Mellitus, Type 2; Disease Progression; Glomerular Filtration Rate; Humans; Kidney; Kidney Tubules; Kidney Tubules, Distal; Kidney Tubules, Proximal; Nitric Oxide Synthase; Renal Circulation; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 1; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Sodium-Hydrogen Exchanger 3
PubMed: 31741437
DOI: 10.1016/j.amjcard.2019.10.027 -
Seminars in Nephrology Nov 2019Renal tissue hypoxia has been implicated as a critical mediatory factor in multiple forms of acute kidney injury (AKI), including in sepsis. In sepsis, whole-kidney... (Review)
Review
Renal tissue hypoxia has been implicated as a critical mediatory factor in multiple forms of acute kidney injury (AKI), including in sepsis. In sepsis, whole-kidney measures of macrocirculatory flow and oxygen delivery appear to be poor predictors of microcirculatory abnormalities. Studies in experimental hyperdynamic septic AKI have shown that the renal medulla is particularly susceptible to hypoxia early in sepsis, even in the presence of increased global renal blood flow and oxygen delivery. It has been proposed that an early onset of progressive renal medullary hypoxia, leading to oxidative stress and inflammation, can initiate a downward spiral of cellular injury culminating in AKI. Recent experimental studies have shown that clinical therapies for septic AKI, including, fluids, vasopressors, and diuretics, have distinct effects on renal macrocirculation and microcirculation. Herein, we review the clinical and experimental evidence of alterations in global and regional kidney perfusion and oxygenation during septic AKI and associated therapies. We justify the need for investigation of the effects of therapies on renal microcirculatory perfusion and oxygenation. We propose that interventions that do not worsen the underlying renal pathophysiologic and reparative processes in sepsis will reduce the development and/or progression of AKI more effectively.
Topics: Acute Kidney Injury; Animals; Disease Management; Diuretics; Fluid Therapy; Humans; Hyperbaric Oxygenation; Kidney Medulla; Microcirculation; Oxidative Stress; Renal Circulation; Sepsis; Vasoconstrictor Agents
PubMed: 31836037
DOI: 10.1016/j.semnephrol.2019.10.004 -
Seminars in Nephrology Nov 2019Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent inherited kidney disease, characterized by growth of bilateral renal cysts, hypertension, and... (Review)
Review
Autosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent inherited kidney disease, characterized by growth of bilateral renal cysts, hypertension, and multiple extrarenal complications that eventually can lead to renal failure. It is caused by mutations in PKD1 or PKD2 genes encoding the proteins polycystin-1 and polycystin-2, respectively. Over the past few years, studies investigating the role of primary cilia and polycystins, present not only on the surface of renal tubular cells but also on vascular endothelial cells, have advanced our understanding of the pathogenesis of ADPKD and have shown that mechanisms other than cyst formation also contribute to renal functional decline in this disease. Among them, increased oxidative stress, endothelial dysfunction, and hypoxia may play central roles because they occur early in the disease process and precede the onset of hypertension and renal functional decline. Endothelial dysfunction is linked to higher asymmetric dimethylarginine levels and reduced nitric oxide bioavailability, which would cause regional vasoconstriction and impaired renal blood flow. The resulting hypoxia would increase the levels of hypoxia-inducible-transcription factor 1α and other angiogenetic factors, which, in turn, may drive cyst growth. In this review, we summarize the existing evidence for roles of endothelial dysfunction, oxidative stress, and hypoxia in the pathogenesis of ADPKD.
Topics: Disease Progression; Endothelium, Vascular; Humans; Hypoxia; Kidney; Oxidative Stress; Polycystic Kidney, Autosomal Dominant; Renal Circulation; Vasoconstriction
PubMed: 31836042
DOI: 10.1016/j.semnephrol.2019.10.009