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Physiological Reports Aug 2022Exercise is restricted for individuals with reduced renal function because exercising reduces blood flow to the kidneys. Safe and effective exercise programs for...
Exercise is restricted for individuals with reduced renal function because exercising reduces blood flow to the kidneys. Safe and effective exercise programs for individuals with reduced renal function have not yet been developed. We previously examined the relationship between exercise intensity and renal blood flow (RBF), revealing that moderate-intensity exercise did not reduce RBF. Determining the effects of exercise duration on RBF may have valuable clinical applications. The current study examined the effects of a single bout of continuous exercise at lactate threshold (LT) intensity on renal hemodynamics. Eight adult males participated in this study. Participants underwent 30 min of aerobic exercise at LT intensity using a cycle ergometer. Evaluation of renal hemodynamics was performed before and after exercise, in the recovery phase using ultrasound echo. Furthermore, blood and urine samplings were conducted before and after exercise, in the recovery phase. Compared with resting, RBF was not significantly changed immediately after continuous exercise (319 ± 102 vs. 308 ± 79 ml/min; p = 0.976) and exhibited no significant changes in the recovery phase. Moreover, urinary kidney injury molecule-1 (uKIM-1) level exhibited no significant change immediately after continuous exercise (0.52 ± 0.20 vs. 0.46 ± 0.27 μg/g creatinine; p = 0.447). In addition, the results revealed no significant change in urinary uKIM-1 in 60-min after exercise. Other renal injury biomarkers exhibited a similar pattern. These findings indicate that a single bout of moderate-intensity continuous exercise maintains RBF and does not induce renal injury.
Topics: Adult; Creatinine; Exercise; Hemodynamics; Humans; Kidney; Male; Renal Circulation
PubMed: 35924347
DOI: 10.14814/phy2.15420 -
Physiology (Bethesda, Md.) May 2015Occlusive renovascular disease caused by atherosclerotic renal artery stenosis (ARAS) elicits complex biological responses that eventually lead to loss of kidney... (Review)
Review
Occlusive renovascular disease caused by atherosclerotic renal artery stenosis (ARAS) elicits complex biological responses that eventually lead to loss of kidney function. Recent studies indicate a complex interplay of oxidative stress, endothelial dysfunction, and activation of fibrogenic and inflammatory cytokines as a result of atherosclerosis, hypoxia, and renal hypoperfusion in this disorder. Human studies emphasize the limits of the kidney adaptation to reduced blood flow, eventually leading to renal hypoxia with activation of inflammatory and fibrogenic pathways. Several randomized prospective clinical trials show that stent revascularization alone in patients with atherosclerotic renal artery stenosis provides little additional benefit to medical therapy once these processes have developed and solidified. Experimental data now support developing adjunctive cell-based measures to support angiogenesis and anti-inflammatory renal repair mechanisms. These data encourage the study of endothelial progenitor cells and/or mesenchymal stem/stromal cells for the repair of damaged kidney tissue.
Topics: Animals; Chronic Disease; Humans; Ischemia; Kidney; Mesenchymal Stem Cell Transplantation; Neovascularization, Physiologic; Regeneration; Renal Artery Obstruction; Renal Circulation; Reperfusion Injury; Treatment Outcome
PubMed: 25933818
DOI: 10.1152/physiol.00065.2013 -
Cells Sep 2022Autophagy eliminates excessive nutrients and maintains homeostasis. Obesity and metabolic syndrome (MetS) dysregulate autophagy, possibly partly due to mitochondria...
Autophagy eliminates excessive nutrients and maintains homeostasis. Obesity and metabolic syndrome (MetS) dysregulate autophagy, possibly partly due to mitochondria injury and inflammation. Elamipretide (ELAM) improves mitochondrial function. We hypothesized that MetS blunts kidney autophagy, which ELAM would restore. Domestic pigs were fed a control or MetS-inducing diet for 16 weeks. During the 4 last weeks, MetS pigs received subcutaneous injections of ELAM (0.1 mg/kg/day, MetS + ELAM) or vehicle (MetS), and kidneys were then harvested to measure protein expression of autophagy mediators and apoptosis. Systemic and renal venous levels of inflammatory cytokines were measured to calculate renal release. The function of isolated mitochondria was assessed by oxidative stress, energy production, and pro-apoptotic activity. MetS slightly downregulated renal expression of autophagy mediators including p62, ATG5-12, mTOR, and AMPK vs. control. Increased mitochondrial HO production accompanied decreased ATP production, elevated apoptosis, and renal fibrosis. In MetS + ELAM, mito-protection restored autophagic protein expression, improved mitochondrial energetics, and blunted renal cytokine release and fibrosis. In vitro, mitoprotection restored mitochondrial membrane potential and reduced oxidative stress in injured proximal tubular epithelial cells. Our study suggests that swine MetS mildly affects renal autophagy, possibly secondary to mitochondrial damage, and may contribute to kidney structural damage in MetS.
Topics: AMP-Activated Protein Kinases; Adenosine Triphosphate; Animals; Autophagy; Cytokines; Epithelial Cells; Fibrosis; Hydrogen Peroxide; Kidney; Metabolic Syndrome; Oligopeptides; Renal Circulation; Sus scrofa; Swine; TOR Serine-Threonine Kinases
PubMed: 36139466
DOI: 10.3390/cells11182891 -
European Review For Medical and... Dec 2020This study aimed to explore the significance of renal Doppler ultrasound in evaluating systemic and renal perfusion in sepsis patients before and after fluid...
OBJECTIVE
This study aimed to explore the significance of renal Doppler ultrasound in evaluating systemic and renal perfusion in sepsis patients before and after fluid resuscitation.
PATIENTS AND METHODS
Forty sepsis patients admitted to the Department of Intensive Medicine and intensive care unit (ICU) of the Fourth Hospital of Hebei Medical University from June 2014 to December 2014 were enrolled in this study, and 35 patients were included in the final analysis. These patients were divided into positive and negative fluid responsiveness groups. They were also divided into an acute kidney injury (AKI) group and a non-AKI group according to changes in creatinine and urine volume. The correlations of the changes in hemodynamics before and after fluid resuscitation in each group with the changes in renal resistance index (RRI) and renal blood flow (RBF) grades were evaluated.
RESULTS
Before and after fluid resuscitation, the heart rate (HR), blood creatinine (Cre), and lactate (Lac) levels of all patients, including the patients in the positive fluid responsiveness group decreased, and the stroke volume (SV) and central venous pressure (CVP) increased. Only HR decreased in the negative fluid responsiveness group. In the AKI group, HR, Cre, and Lac decreased, while in the non-AKI group, HR decreased, but CVP and SV increased. There were differences between HR, Lac, and change rate of Lac (Lac%) after fluid resuscitation for the positive and negative fluid responsiveness groups. There was no statistical difference between the RRI values of each group before and after fluid resuscitation. The RRI values of the AKI group were higher than those of the non-AKI group, while the AKI group's RBF grades were lower than those of the non-AKI group. The change rate of RRI (RRI%) was higher in the AKI group than in the non-AKI group. Except for the negative fluid responsiveness group, the RBF grade of each group increased.
CONCLUSIONS
The approach of RBF classification based on Doppler ultrasound can be used to evaluate the systemic and renal perfusion of patients with severe sepsis before and after fluid resuscitation, while the RRI value cannot be used for evaluation. However, the RRI value can be used as a dynamic index for the evaluation of renal perfusion in patients with AKI.
Topics: Acute Kidney Injury; Aged; Female; Fluid Therapy; Hemodynamics; Humans; Intensive Care Units; Kidney Function Tests; Male; Middle Aged; Perfusion; Renal Circulation; Sepsis; Ultrasonography, Doppler; Vascular Resistance
PubMed: 33336787
DOI: 10.26355/eurrev_202012_24040 -
Methods in Molecular Biology (Clifton,... 2021Dynamic contrast-enhanced (DCE) MRI monitors the transit of contrast agents, typically gadolinium chelates, through the intrarenal regions, the renal cortex, the...
Dynamic contrast-enhanced (DCE) MRI monitors the transit of contrast agents, typically gadolinium chelates, through the intrarenal regions, the renal cortex, the medulla, and the collecting system. In this way, DCE-MRI reveals the renal uptake and excretion of the contrast agent. An optimal DCE-MRI acquisition protocol involves finding a good compromise between whole-kidney coverage (i.e., 3D imaging), spatial and temporal resolution, and contrast resolution. By analyzing the enhancement of the renal tissues as a function of time, one can determine indirect measures of clinically important single-kidney parameters as the renal blood flow, glomerular filtration rate, and intrarenal blood volumes. Gadolinium-containing contrast agents may be nephrotoxic in patients suffering from severe renal dysfunction, but otherwise DCE-MRI is clearly useful for diagnosis of renal functions and for assessing treatment response and posttransplant rejection.Here we introduce the concept of renal DCE-MRI, describe the existing methods, and provide an overview of preclinical DCE-MRI applications to illustrate the utility of this technique to measure renal perfusion and glomerular filtration rate in animal models.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction is complemented by two separate publications describing the experimental procedure and data analysis.
Topics: Animals; Biomarkers; Contrast Media; Diffusion Magnetic Resonance Imaging; Glomerular Filtration Rate; Humans; Image Enhancement; Image Processing, Computer-Assisted; Kidney; Monitoring, Physiologic; Perfusion; Renal Circulation; Software
PubMed: 33476002
DOI: 10.1007/978-1-0716-0978-1_12 -
Hypertension (Dallas, Tex. : 1979) Apr 2022The collateral circulation can adapt to bypass major arteries with limited flow and serves a crucial protective role in coronary, cerebral, and peripheral arterial... (Review)
Review
The collateral circulation can adapt to bypass major arteries with limited flow and serves a crucial protective role in coronary, cerebral, and peripheral arterial disease. Emerging evidence indicates that the renal collateral circulation can similarly adapt and thereby limit kidney ischemia in atherosclerotic renovascular disease. These adaptations predominantly include recruitment of preexisting microvessels for arteriogenesis, with de novo vessel formation playing a limited role. Yet, adaptations of the renal collateral circulation in renovascular disease are often insufficient to fully compensate for the limited flow within an obstructed renal artery and may be hampered by the severity of obstruction or patient comorbidities. Experimental strategies have attempted to circumvent limitations of collateral formation and improve the prognosis of patients with various ischemic vascular territories. These have included pharmacological approaches such as endothelial growth factors, renin-angiotensin-aldosterone system blockade, and I channel-blockers, as well as interventions like preconditioning, exercise, enhanced external counter-pulsation, and low-energy shock-wave therapy. However, few of these strategies have been implemented in atherosclerotic renovascular disease. This review summarizes current understanding regarding the development of renal collateral circulation in atherosclerotic renovascular disease. Studies are needed to apply lessons learned in other vascular beds in the setting of atherosclerotic renovascular disease to develop new treatment regimens for this patient group.
Topics: Atherosclerosis; Collateral Circulation; Female; Humans; Hypertension, Renovascular; Ischemia; Kidney; Kidney Diseases; Male; Renal Artery; Renal Artery Obstruction; Renal Circulation
PubMed: 35135307
DOI: 10.1161/HYPERTENSIONAHA.121.17960 -
Critical Care (London, England) Apr 2017Acute kidney injury (AKI) occurs frequently after liver transplantation and is associated with the development of chronic kidney disease and increased mortality. There... (Clinical Trial)
Clinical Trial
BACKGROUND
Acute kidney injury (AKI) occurs frequently after liver transplantation and is associated with the development of chronic kidney disease and increased mortality. There is a lack of data on renal blood flow (RBF), oxygen consumption, glomerular filtration rate (GFR) and renal oxygenation, i.e. the renal oxygen supply/demand relationship, early after liver transplantation. Increased insight into the renal pathophysiology after liver transplantation is needed to improve the prevention and treatment of postoperative AKI. We have therefore studied renal hemodynamics, function and oxygenation early after liver transplantation in humans.
METHODS
Systemic hemodynamic and renal variables were measured during two 30-min periods in liver transplant recipients (n = 12) and post-cardiac surgery patients (controls, n = 73). RBF and GFR were measured by the renal vein retrograde thermodilution technique and by renal extraction of Cr-EDTA (= filtration fraction), respectively. Renal oxygenation was estimated from the renal oxygen extraction.
RESULTS
In the liver transplant group, GFR decreased by 40% (p < 0.05), compared to the preoperative value. Cardiac index and systemic vascular resistance index were 65% higher (p < 0.001) and 36% lower (p < 0.001), respectively, in the liver transplant recipients compared to the control group. GFR was 27% (p < 0.05) and filtration fraction 40% (p < 0.01) lower in the liver transplant group. Renal vascular resistance was 15% lower (p < 0.05) and RBF was 18% higher (p < 0.05) in liver transplant recipients, but the ratio between RBF and cardiac index was 27% lower (p < 0.001) among the liver-transplanted patients compared to the control group. Renal oxygen consumption and extraction were both higher in the liver transplants, 44% (p < 0.01) and 24% (p < 0.05) respectively.
CONCLUSIONS
Despite the hyperdynamic systemic circulation and renal vasodilation, there is a severe decline in renal function directly after liver transplantation. This decline is accompanied by an impaired renal oxygenation, as the pronounced elevation of renal oxygen consumption is not met by a proportional increase in renal oxygen delivery. This information may provide new insights into renal pathophysiology as a basis for future strategies to prevent/treat AKI after liver transplantation.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02455115 . Registered on 23 April 2015.
Topics: Acute Kidney Injury; Aged; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney; Linear Models; Liver Transplantation; Male; Middle Aged; Oxygen Consumption; Renal Circulation; Statistics, Nonparametric; Vascular Resistance
PubMed: 28395663
DOI: 10.1186/s13054-017-1675-4 -
American Journal of Physiology. Renal... Jul 2015This article reviews the pioneering and visionary contributions of the Catalan surgeon Josep Trueta (1897–1977) to the changes in renal circulation that contribute to... (Review)
Review
This article reviews the pioneering and visionary contributions of the Catalan surgeon Josep Trueta (1897–1977) to the changes in renal circulation that contribute to the pathogenesis of acute renal failure (ARF). An erudite scientist with eclectic interests in physiology, orthopedics, politics, and medical history, Trueta's initial involvement in wound healing as a trauma surgeon during the Spanish Civil War and the London Blitz is what prompted him to postulate that a trauma-induced “neural effect” on the renal vasculature, with resultant renal arterial constriction could cause ARF. To test his hypothesis, Trueta assembled an experienced radiologist, a renowned physiologist, and a renal pathologist to study ARF in Oxford. They investigated the renal circulation of rabbits in response to diverse traumatic conditions by injecting a radio-opaque substance, using cine-radiography to visualize the flow of blood through the renal vasculature. Trueta's suggestion of renal cortical ischemia and diversion of blood to the less resistant medullary circulation (Trueta shunt) was criticized by Homer Smith and coworkers. In contrast to Homer Smith's data, which were derived from clearance studies and renal arteriovenous oxygen, Trueta used the diametrical opposite method of “direct” observation of the renal circulation. Their differing methodologies, direct visualization of the renal circulation as opposed to inferred computations from clearance studies, accounts for some of their conflicting theories. Nevertheless, the proposal of disparate renal flow compartments focused attention on intrarenal hemodynamics. Trueta's focus on renal cortical ischemia was ultimately validated by the studies of Barger in the dog and Hollenberg and Epstein in human subjects.
Topics: Acute Kidney Injury; Animals; Biomedical Research; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Nephrology; Renal Circulation
PubMed: 25995107
DOI: 10.1152/ajprenal.00075.2015 -
Journal of the American Society of... Sep 2015Results of recent clinical trials and experimental studies indicate that whereas atherosclerotic renovascular disease can accelerate both systemic hypertension and... (Review)
Review
Results of recent clinical trials and experimental studies indicate that whereas atherosclerotic renovascular disease can accelerate both systemic hypertension and tissue injury in the poststenotic kidney, restoring vessel patency alone is insufficient to recover kidney function for most subjects. Kidney injury in atherosclerotic renovascular disease reflects complex interactions among vascular rarefication, oxidative stress injury, and recruitment of inflammatory cellular elements that ultimately produce fibrosis. Classic paradigms for simply restoring blood flow are shifting to implementation of therapy targeting mitochondria and cell-based functions to allow regeneration of vascular, glomerular, and tubular structures sufficient to recover, or at least stabilize, renal function. These developments offer exciting possibilities of repair and regeneration of kidney tissue that may limit progressive CKD in atherosclerotic renovascular disease and may apply to other conditions in which inflammatory injury is a major common pathway.
Topics: Atherosclerosis; Hemodynamics; Humans; Ischemia; Kidney; Mitochondria; Nephritis; Oxidative Stress; Renal Artery Obstruction; Renal Circulation; Renal Insufficiency, Chronic
PubMed: 25868641
DOI: 10.1681/ASN.2014121274 -
American Journal of Physiology. Renal... Mar 2021Renal autoregulation is critical in maintaining stable renal blood flow (RBF) and glomerular filtration rate (GFR). Renal ischemia-reperfusion (IR)-induced kidney injury...
Renal autoregulation is critical in maintaining stable renal blood flow (RBF) and glomerular filtration rate (GFR). Renal ischemia-reperfusion (IR)-induced kidney injury is characterized by reduced RBF and GFR. The mechanisms contributing to renal microvascular dysfunction in IR have not been fully determined. We hypothesized that increased reactive oxygen species (ROS) contributed to impaired renal autoregulatory capability in IR rats. Afferent arteriolar autoregulatory behavior was assessed using the blood-perfused juxtamedullary nephron preparation. IR was induced by 60 min of bilateral renal artery occlusion followed by 24 h of reperfusion. Afferent arterioles from sham rats exhibited normal autoregulatory behavior. Stepwise increases in perfusion pressure caused pressure-dependent vasoconstriction to 65 ± 3% of baseline diameter (13.2 ± 0.4 μm) at 170 mmHg. In contrast, pressure-mediated vasoconstriction was markedly attenuated in IR rats. Baseline diameter averaged 11.7 ± 0.5 µm and remained between 90% and 101% of baseline over 65-170 mmHg, indicating impaired autoregulatory function. Acute antioxidant administration (tempol or apocynin) to IR kidneys for 20 min increased baseline diameter and improved autoregulatory capability, such that the pressure-diameter profiles were indistinguishable from those of sham kidneys. Furthermore, the addition of polyethylene glycol superoxide dismutase or polyethylene glycol-catalase to the perfusate blood also restored afferent arteriolar autoregulatory responsiveness in IR rats, indicating the involvement of superoxide and/or hydrogen peroxide. IR elevated mRNA expression of NADPH oxidase subunits and monocyte chemoattractant protein-1 in renal tissue homogenates, and this was prevented by tempol pretreatment. These results suggest that ROS accumulation, likely involving superoxide and/or hydrogen peroxide, impairs renal autoregulation in IR rats in a reversible fashion. Renal ischemia-reperfusion (IR) leads to renal microvascular dysfunction manifested by impaired afferent arteriolar autoregulatory efficiency. Acute administration of scavengers of reactive oxygen species, polyethylene glycol-superoxide dismutase, or polyethylene glycol-catalase following renal IR restored afferent arteriolar autoregulatory capability in IR rats, indicating that renal IR led to reversible impairment of afferent arteriolar autoregulatory capability. Intervention with antioxidant treatment following IR may improve outcomes in patients by preserving renovascular autoregulatory function and potentially preventing the progression to chronic kidney disease after acute kidney injury.
Topics: Animals; Arterioles; Blood Pressure; Glomerular Filtration Rate; Homeostasis; NADPH Oxidases; Rats; Reactive Oxygen Species; Renal Circulation; Renal Insufficiency, Chronic; Reperfusion Injury
PubMed: 33491564
DOI: 10.1152/ajprenal.00500.2020