A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion

Author(s):  
Ilias P. Doulamis ◽  
Alvise Guariento ◽  
Mossab Y. Saeed ◽  
Rio S. Nomoto ◽  
Thomas Duignan ◽  
...  
2020 ◽  
Vol 6 (6) ◽  
pp. 453-460
Author(s):  
Michael W. Dae ◽  
Kathleen D. Liu ◽  
Richard J. Solomon ◽  
Dong W. Gao ◽  
Carol A. Stillson

<b><i>Introduction:</i></b> Post-contrast acute kidney injury (PC-AKI) develops in a significant proportion of patients with CKD after invasive cardiology procedures and is strongly associated with adverse outcomes. <b><i>Objective:</i></b> We sought to determine whether increased intrarenal nitric oxide (NO) would prevent PC-AKI. <b><i>Methods:</i></b> To create a large animal model of CKD, we infused 250 micron particles into the renal arteries in 56 ± 8 kg pigs. We used a low-frequency therapeutic ultrasound device (LOTUS – 29 kHz, 0.4 W/cm<sup>2</sup>) to induce NO release. NO and laser Doppler probes were used to assess changes in NO content and blood flow. Glomerular filtration rate (GFR) was measured by technetium-diethylene-triamine-pentaacetic acid (Tc-99m-DTPA) radionuclide imaging. PC-AKI was induced by intravenous infusion of 7 cm<sup>3</sup>/kg diatrizoate. In patients with CKD, we measured GFR at baseline and during LOTUS using Tc-99m--DTPA radionuclide imaging. <b><i>Results:</i></b> In the pig model, CKD developed over 4 weeks (serum creatinine [Cr], mg/dL, 1.0 ± 0.2–2.6 ± 0.9, <i>p</i> &#x3c; 0.01, <i>n</i> = 12). NO and renal blood flow (RBF) increased in cortex and medulla during LOTUS. GFR increased 75 ± 24% (<i>p</i> = 0.016, <i>n</i> = 3). PC-AKI developed following diatrizoate i.v. infusion (Cr 2.6 ± 0.7 baseline to 3.4 ± 0.6 at 24 h, <i>p</i> &#x3c; 0.01, <i>n</i> = 3). LOTUS (starting 15 min prior to contrast and lasting for 90 min) prevented PC-AKI in the same animals 1 week later (Cr 2.5 ± 0.4 baseline to 2.6 ± 0.7 at 24 h, <i>p</i> = ns, <i>n</i> = 3). In patients with CKD (<i>n</i> = 10), there was an overall 25% increase in GFR in response to LOTUS (<i>p</i> &#x3c; 0.01). <b><i>Conclusions:</i></b> LOTUS increased intrarenal NO, RBF, and GFR and prevented PC-AKI in a large animal model of CKD, and significantly increased GFR in patients with CKD. This novel approach may provide a noninvasive nonpharmacological means to prevent PC-AKI in high-risk patients.


2014 ◽  
Vol 4 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Niina Koivuviita ◽  
Risto Tertti ◽  
Maija Heiro ◽  
Ilkka Manner ◽  
Kaj Metsärinne

2021 ◽  
pp. 153537022098175
Author(s):  
Si-Yang Wang ◽  
Chao-Yang Zhang ◽  
Guang-Yan Cai ◽  
Xiang-Mei Chen

Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.


Author(s):  
Tim Raine ◽  
James Dawson ◽  
Stephan Sanders ◽  
Simon Eccles

Acute kidney injuryChronic renal failureHaematuriaProteinuriaGlomerular diseaseUrological disordersLow urine outputIV fluidsPotassium emergenciesElectrolyte imbalanceAcute rise from baseline of serum urea and creatinine ±oliguria ( Table 12.1);1there are three basic mechanisms:•Prerenal hypoperfusion of kidney due to eg ↓BP, hypovolaemia, renal artery occlusion (mass, emboli)...


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Angela Castellanos Rieger ◽  
Bryon A Tompkins ◽  
Makoto Natsumeda ◽  
Victoria Florea ◽  
Kevin Collon ◽  
...  

Background: Chronic Kidney Disease (CKD) is an independent risk factor for cardiovascular morbidity and mortality. Left ventricular (LV) hypertrophy and heart failure with preserved ejection fraction (HFpEF) are the primary manifestations of the cardiorenal syndrome in 60 to 80% of CKD patients. Therapies that improve morbidity and mortality in HFpEF are lacking. Stem cell therapy reduces fibrosis, increases neovascularization, and promotes cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that stem cell treatment ameliorates HFpEF in a CKD model. Methods: Yorkshires pigs (n=27) underwent 5/6 nephrectomy via renal artery embolization and 4-weeks later received either: allogeneic (allo-) MSC (10х10 6 ), allo-kidney c-kit + cells (c-kit; 10х10 6 ), combination (MSC+c-kit; 1:1 ratio [5х10 6 each]), or placebo (each n=5). Cell therapy was delivered via the patent renal artery. Kidney function, renal and cardiac MRI, and PV loops were measured at baseline, and at 4- and 12-weeks (euthanasia) post-embolization. Results: The CKD model was confirmed by increased creatinine and BUN and decreased GFR. Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks (p=0.7). HFpEF was demonstrated at 4 weeks by increased LV mass (20.3%; p= 0.0001), wall thickening (p<0.008), EDP (p=0.01), EDPVR (p=0.005), and arterial elastance (p=0.03), with no change in EF. Diffuse intramyocardial fibrosis was evident in histological analysis and delayed enhancement MRI imaging. After 12 weeks, there was a significant difference in MAP between groups (p=0.04), with an increase in the placebo group (19.97± 8.65 mmHg, p=0.08). GFR significantly improved in the combination group (p=0.033). EDV increased in the placebo (p=0.009) and c-kit (p=0.004) groups. ESV increased most in the placebo group (7.14±1.62ml; p=0.022). EF, wall thickness, and LV mass did not differ between groups at 12 weeks. Conclusion: A CKD large animal model manifests the characteristics of HFpEF. Intra-renal artery allogeneic cell therapy was safe. A beneficial effect of cell therapy was observed in the combination and MSC groups. These findings have important implications on the use of cell therapy for HFpEF and cardiorenal syndrome.


Renal Failure ◽  
1998 ◽  
Vol 20 (1) ◽  
pp. 157-162 ◽  
Author(s):  
R. C. Abdulkader ◽  
M. O. Avila ◽  
L. B. Saldanha ◽  
A. M. Ab'saber ◽  
E. A. Burdman

2019 ◽  
Vol 11 (3) ◽  
pp. 468-480 ◽  
Author(s):  
Mohammed Salman Shazeeb ◽  
Robert M. King ◽  
Olivia W. Brooks ◽  
Ajit S. Puri ◽  
Nils Henninger ◽  
...  

2010 ◽  
Vol 51 (3) ◽  
pp. 720-724 ◽  
Author(s):  
Kaan Inan ◽  
Alper Ucak ◽  
Burak Onan ◽  
Veysel Temizkan ◽  
Murat Ugur ◽  
...  

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