Renal circulatory occlusion and local cooling

A method was developed for local kidney cooling in vivo, evaluated in dogs and applied clinically. In dogs a reversible lesion was not obtained if renal ischemia lasted beyond 1 hour at 37℃. Application of local cooling (10±5℃) extended the tolerance time to 7 hours, with clamping of the entire renal pedicle, and to 12 hours with occlusion of the renal artery alone. Exposure of the same kidney to a second occlusion period (up to 9 hr.) resulted in a reversible lesion. Renal function studies (CU, CIn, CPAH and TmPAH) showed the same pattern (initial depression and course of recovery) as after renal ischemia at body temperature. Initial depression was roughly paralleling the duration of clamping. Preischemic function values were, in most instances, reached 3 months following the experimental procedure. Physiological aspects of ‘local cooling’ are discussed and the advantages over general hypothermia are pointed out. The technique used for clinical application is described. Submitted on April 25, 1958

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Successful Repair of Acute Type B and Retrograde Type A Aortic Dissection With Kidney Ischemia

Vascular and Endovascular Surgery ◽

10.1177/1538574417708133 ◽

2017 ◽

Vol 51 (5) ◽

pp. 342-345 ◽

Cited By ~ 1

Author(s):

Jeko M. Madjarov ◽

Michael G. Katz ◽

Hector Crespo-Soto ◽

Svetozar Madzharov ◽

Timothy Roush ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Aortic Dissection ◽

Renal Artery ◽

Kidney Injury ◽

Renal Ischemia ◽

Left Renal Artery ◽

Acute Type ◽

Type B ◽

Type A Aortic Dissection

Acute dissection of thoracic aorta carries a risk of renal ischemia followed by the development of a kidney failure. The optimal surgical and nonsurgical management of these patients, timing of intervention, and the factors predicting renal recovery are not well delineated and remain controversial. We present a case of acute type B thoracic aortic dissection with left kidney ischemia. Evaluation of renal function was performed by the means of internationally accepted Risk, Injury, Failure, Loss of kidney function, End stage kidney disease and Acute Kidney Injury Network classifications for acute kidney injury, renal duplex sonography, and intravascular ultrasound that demonstrated left renal artery dissection with a flap completely compressing the true lumen. The patient underwent thoracic endovascular aortic repair and left renal artery stent and recovered well. Six months later, at the follow-up visit, retrograde type A aortic dissection was found, which was successfully repaired. Reversal of renal ischemia after aortic dissection depends on the precise assessment of renal function and prompt intervention.

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A1 adenosine receptor knockout mice exhibit increased renal injury following ischemia and reperfusion

AJP Renal Physiology ◽

10.1152/ajprenal.00185.2003 ◽

2004 ◽

Vol 286 (2) ◽

pp. F298-F306 ◽

Cited By ~ 104

Author(s):

H. Thomas Lee ◽

Hua Xu ◽

Samih H. Nasr ◽

Jurgen Schnermann ◽

Charles W. Emala

Keyword(s):

Renal Function ◽

Knockout Mice ◽

Adenosine Receptor ◽

Renal Injury ◽

Renal Ischemia ◽

Myeloperoxidase Activity ◽

Ischemia And Reperfusion ◽

Wild Type Littermate ◽

Renal Histology

Controversy exists regarding the effect of A1 adenosine receptor (AR) activation in the kidney during ischemia and reperfusion (I/R) injury. We sought to further characterize the role of A1 ARs in modulating renal function after I/R renal injury using both pharmacological and gene deletion approaches in mice. A1 AR knockout mice (A1KO) or their wild-type littermate controls (A1WT) were subjected to 30 min of renal ischemia. Some A1WT mice were subjected to 30 min of renal ischemia with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) or 2-chrolo-cyclopentyladenosine (CCPA), selective A1 AR antagonist and agonist, respectively. Plasma creatinine and renal histology were compared 24 h after renal injury. A1KO mice exhibited significantly higher creatinines and worsened renal histology compared with A1WT controls following renal I/R injury. A1WT mice pretreated with the A1 AR antagonist or agonist demonstrated significantly worsened or improved renal function, respectively, after I/R injury. In addition, A1WT mice pretreated with DPCPX or CCPA showed significantly increased or reduced markers of renal inflammation, respectively (renal myeloperoxidase activity, renal tubular neutrophil infiltration, ICAM-1, TNF-α, and IL-1β mRNA expression), while demonstrating no differences in indicators of apoptosis. In conclusion, we demonstrate that endogenous or exogenous preischemic activation of A1 ARs protects against renal I/R injury in vivo via mechanisms leading to decreased necrosis and inflammation.

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Trehalose attenuates renal ischemia-reperfusion injury by enhancing autophagy and inhibiting oxidative stress and inflammation

AJP Renal Physiology ◽

10.1152/ajprenal.00568.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. F994-F1005

Author(s):

Suwen Liu ◽

Yunwen Yang ◽

Huiping Gao ◽

Ning Zhou ◽

Peipei Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Renal Function ◽

Renal Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Renal Ischemia ◽

Renal Histology ◽

Hypoxia Reoxygenation

Renal ischemia-reperfusion (IR) injury is one of the most common acute kidney injuries, but there is still a lack of effective treatment in the clinical setting. Trehalose (Tre), a natural disaccharide, has been demonstrated to protect against oxidative stress, inflammation, and apoptosis. However, whether it could protect against IR-induced renal injury needs to be investigated. In an in vivo experiment, C57BL/6J mice were pretreated with or without Tre (2 g/kg) through a daily single intraperitoneal injection from 3 days before renal IR surgery. Renal function, apoptosis, oxidative stress, and inflammation were analyzed to evaluate kidney injury. In an in vitro experiment, mouse proximal tubular cells were treated with or without Tre under a hypoxia/reoxygenation condition. Western blot analysis, autophagy flux detection, and apoptosis assay were performed to evaluate the level of autophagy and antiapoptotic effect of Tre. The in vivo results showed that the renal damage induced by IR was ameliorated by Tre treatment, as renal histology and renal function were improved and the enhanced protein levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were blocked. Moreover, autophagy was activated by Tre pretreatment along with inhibition of the IR injury-induced apoptosis, oxidative stress, and inflammation. The in vitro results showed that Tre treatment activated autophagy and protected against hypoxia/reoxygenation-induced tubular cell apoptosis and oxidative stress. Our results demonstrated that Tre protects against IR-induced renal injury, possibly by enhancing autophagy and blocking oxidative stress, inflammation, and apoptosis, suggesting its potential use for the clinical treatment of renal IR injury.

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Biopolymer-delivered vascular endothelial growth factor improves renal outcomes following revascularization

AJP Renal Physiology ◽

10.1152/ajprenal.00607.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. F1016-F1025 ◽

Cited By ~ 4

Author(s):

Erika Guise ◽

Jason E. Engel ◽

Maxx L. Williams ◽

Fakhri Mahdi ◽

Gene L. Bidwell ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Renal Function ◽

Growth Factor ◽

Renal Artery ◽

Renal Artery Stenosis ◽

Artery Stenosis ◽

Renal Recovery ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Renal angioplasty and stenting (PTRAs) resolves renal artery stenosis, but inconsistently improves renal function, possibly due to persistent parenchymal damage. We developed a bioengineered fusion of a drug delivery vector (elastin-like polypeptide, ELP) with vascular endothelial growth factor (VEGF), and showed its therapeutic efficacy. We tested the hypothesis that combined ELP-VEGF therapy with PTRAs improves renal recovery more efficiently than PTRAs alone, by protecting the stenotic renal parenchyma. Unilateral renovascular disease (RVD) was induced by renal artery stenosis in 14 pigs. Six weeks later, stenotic kidney blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo using multidetector CT. Blood and urine were collected during in vivo studies. All pigs underwent PTRAs and then were randomized into single intrarenal ELP-VEGF administration or placebo ( n = 7 each) groups. Pigs were observed for four additional weeks, in vivo CT studies were repeated, and then pigs were euthanized for ex vivo studies to quantify renal microvascular (MV) density, angiogenic factor expression, and morphometric analysis. Renal hemodynamics were similarly blunted in all RVD pigs. PTRAs resolved stenosis but modestly improved RBF and GFR. However, combined PTRAs+ ELP-VEGF improved RBF, GFR, regional perfusion, plasma creatinine, asymmetric dimethlyarginine (ADMA), and albuminuria compared with PTRAs alone, accompanied by improved angiogenic signaling, MV density, and renal fibrosis. Greater improvement of renal function via coadjuvant ELP-VEGF therapy may be driven by enhanced MV proliferation and repair, which ameliorates MV rarefaction and fibrogenic activity that PTRAs alone cannot offset. Thus, our study supports a novel strategy to boost renal recovery in RVD after PTRAs.

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Chronic Renal Changes After a Single Ischemic Event in an Experimental Model of Feline Chronic Kidney Disease

Veterinary Pathology ◽

10.1177/0300985819837721 ◽

2019 ◽

Vol 56 (4) ◽

pp. 536-543 ◽

Cited By ~ 4

Author(s):

Cathy A. Brown ◽

Daniel R. Rissi ◽

Vanna M. Dickerson ◽

Anastacia M. Davis ◽

Scott A. Brown ◽

...

Keyword(s):

Renal Function ◽

Structural Changes ◽

Interstitial Fibrosis ◽

Renal Ischemia ◽

Loss Of Function ◽

Tubular Atrophy ◽

Ischemic Event ◽

Tubulointerstitial Lesions ◽

Atubular Glomeruli

Previous work demonstrated renal fibrosis 70 days after a single unilateral in vivo renal ischemic event, but changes associated with a single episode of renal ischemia past this time are unknown. In this study, we evaluated renal function and structural changes 6 months after a 90-minute in vivo unilateral renal ischemic event. Six adult female cats underwent unilateral renal ischemia and renal function was followed for 6 months, at which time the kidneys were evaluated by histology and histomorphometry. Over time, there was a significant reduction in the glomerular filtration rate and an elevation of serum creatinine of 31% and 42%, respectively. All cats had tubulointerstitial lesions characterized by segmental interstitial inflammation, tubular atrophy, and interstitial fibrosis. Unlike short-term studies, ischemic kidneys had variable numbers of obsolescent glomeruli, consistent with the development of atubular glomeruli and subsequent ischemic glomerulosclerosis. Chronic changes associated with acute renal ischemia may include loss of function and glomerulosclerosis.

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Increased progression to kidney fibrosis after erythropoietin is used as a treatment for acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00241.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. F681-F692 ◽

Cited By ~ 24

Author(s):

Glenda C. Gobe ◽

Nigel C. Bennett ◽

Malcolm West ◽

Paul Colditz ◽

Lindsay Brown ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Renal Function ◽

Kidney Disease ◽

Kidney Injury ◽

Renal Ischemia ◽

Acute Injury

Treatment of renal ischemia-reperfusion (IR) injury with recombinant human erythropoietin (rhEPO) reduces acute kidney injury and improves function. We aimed to investigate whether progression to chronic kidney disease associated with acute injury was also reduced by rhEPO treatment, using in vivo and in vitro models. Rats were subjected to bilateral 40-min renal ischemia, and kidneys were studied at 4, 7, and 28 days postreperfusion for renal function, tubular injury and repair, inflammation, and fibrosis. Acute injury was modulated using rhEPO (1,000 or 5,000 IU/kg, intraperitoneally) at the time of reperfusion. Renal tubular epithelial cells or fibroblasts in culture were subjected to hypoxia or oxidative stress, with or without rhEPO (200 IU/ml), and fibrogenesis was studied. The results of the in vivo model confirmed functional and structural improvement with rhEPO at 4 days post-IR ( P < 0.05). At 7 days post-IR, fibrosis and myofibroblast stimulation were increased with IR with and without rhEPO ( P < 0.01). However, at 28 days post-IR, renal fibrosis and myofibroblast numbers were significantly greater with IR plus rhEPO ( P < 0.01) compared with IR only. Mechanistically, rhEPO stimulated profibrotic transforming growth factor-β, oxidative stress (marker 8-hydroxy-deoxyguanosine), and phosphorylation of the signal transduction protein extracellular signal-regulated kinase. In vitro, rhEPO protected tubular epithelium from apoptosis but stimulated epithelial-to-mesenchymal transition and also protected and activated fibroblasts, particularly with oxidative stress. In summary, although rhEPO was protective of renal function and structure in acute kidney injury, the supraphysiological dose needed for renoprotection contributed to fibrogenesis and stimulated chronic kidney disease in the long term.

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Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.5.h1542 ◽

1998 ◽

Vol 275 (5) ◽

pp. H1542-H1547 ◽

Cited By ~ 28

Author(s):

Theresa J. Pell ◽

Gary F. Baxter ◽

Derek M. Yellon ◽

G. Michael Drew

Keyword(s):

Renal Artery ◽

Risk Ratio ◽

Adenosine Receptors ◽

Ischemia Reperfusion ◽

Rabbit Model ◽

Renal Ischemia ◽

Left Renal Artery ◽

Adenosine Receptor Antagonist ◽

Underlying Mechanisms

Brief renal ischemia-reperfusion is reported to precondition the myocardium; however, the underlying mechanisms are unknown. This phenomenon was, therefore, investigated using an in vivo rabbit model of acute myocardial infarction. Characterization of the mechanisms involved was performed using the nonselective adenosine receptor antagonist 8-( p-sulfophenyl)theophylline (8-SPT) and the ATP-sensitive potassium (KATP) channel blocker sodium 5-hydroxydecanoate (5-HD). Pentobarbital-anesthetized rabbits underwent a left thoracotomy and pericardiotomy. A laparotomy was then performed to expose the left renal artery. Animals were either preconditioned with a 10-min occlusion of the renal artery followed by 10 min of reperfusion or underwent a 20-min sham period of anesthesia. Subsequently, the left coronary artery was then occluded for 30 min and reperfused for 2 h. Infarct-to-risk ratio was limited from 32.7 ± 4.0% ( n = 12) in controls to 17.8 ± 3.0% ( n = 9; P = 0.002) in preconditioned hearts. Protection was abolished by 7.5 mg/kg iv 8-SPT (36.7 ± 3.7%; n = 6) or 5 mg/kg iv 5-HD (33.1 ± 4.4%; n = 6) administered before preconditioning. 8-SPT (40.0 ± 4.4%; n = 6) or 5-HD (40.5 ± 4.2%; n = 6) did not affect infarct-to-risk ratio in sham controls. Thus activation of both adenosine receptors and KATP channels appears to be involved in acute renal preconditioning of the myocardium.

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