Method used to establish a large animal model of drug-induced acute kidney injury

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.

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

Journal of Visualized Experiments ◽

10.3791/62230 ◽

2021 ◽

Author(s):

Ilias P. Doulamis ◽

Alvise Guariento ◽

Mossab Y. Saeed ◽

Rio S. Nomoto ◽

Thomas Duignan ◽

...

Keyword(s):

Acute Kidney Injury ◽

Animal Model ◽

Renal Artery ◽

Kidney Injury ◽

Artery Occlusion ◽

Large Animal Model ◽

Large Animal ◽

Renal Artery Occlusion ◽

Bilateral Renal Artery

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Effect of Low-Frequency Therapeutic Ultrasound on Induction of Nitric Oxide in CKD: Potential to Prevent Acute Kidney Injury

Kidney Diseases ◽

10.1159/000509819 ◽

2020 ◽

Vol 6 (6) ◽

pp. 453-460

Author(s):

Michael W. Dae ◽

Kathleen D. Liu ◽

Richard J. Solomon ◽

Dong W. Gao ◽

Carol A. Stillson

Keyword(s):

Nitric Oxide ◽

Acute Kidney Injury ◽

Animal Model ◽

Blood Flow ◽

Radionuclide Imaging ◽

Therapeutic Ultrasound ◽

Low Frequency ◽

Kidney Injury ◽

Large Animal Model ◽

Large Animal

Introduction: 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. Objective: We sought to determine whether increased intrarenal nitric oxide (NO) would prevent PC-AKI. Methods: 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/cm2) 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 cm3/kg diatrizoate. In patients with CKD, we measured GFR at baseline and during LOTUS using Tc-99m--DTPA radionuclide imaging. Results: In the pig model, CKD developed over 4 weeks (serum creatinine [Cr], mg/dL, 1.0 ± 0.2–2.6 ± 0.9, p < 0.01, n = 12). NO and renal blood flow (RBF) increased in cortex and medulla during LOTUS. GFR increased 75 ± 24% (p = 0.016, n = 3). PC-AKI developed following diatrizoate i.v. infusion (Cr 2.6 ± 0.7 baseline to 3.4 ± 0.6 at 24 h, p < 0.01, n = 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, p = ns, n = 3). In patients with CKD (n = 10), there was an overall 25% increase in GFR in response to LOTUS (p < 0.01). Conclusions: 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.

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Spontaneous Partial Recovery of Striatal Dopaminergic Uptake Despite Nigral Cell Loss in Asymptomatic MPTP-Lesioned Minipigs

10.21203/rs.3.rs-620635/v1 ◽

2021 ◽

Author(s):

Anne M. Landau ◽

Thea P. Lillethorup ◽

Ove Noer ◽

Aage Kristian Olsen Alstrup ◽

Kathrine Stokholm ◽

...

Keyword(s):

Animal Model ◽

Spontaneous Recovery ◽

Ethical Issues ◽

Cell Loss ◽

Large Animal Model ◽

Large Animal ◽

Partial Recovery ◽

Behavioral Deficits ◽

Large Animal Models ◽

Human Primate

Abstract The gold standard animal model of Parkinson’s disease is the non-human primate rendered parkinsonian with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin. Low availability, ethical issues, and primate-specific biohazards make alternative large animal models necessary. Here, we investigate the temporal evolution of presynaptic dopaminergic function after MPTP in another large animal model, the Göttingen minipig. We subcutaneously injected seven sedated minipigs with 1–2 mg/kg of MPTP, and two minipigs with saline, three times a week over 4 weeks. We monitored behavioral deficits using a validated motor scale and a Gait4Dog® walking mat. Minipig brains were imaged with (+)-⍺-[11C]-dihydrotetrabenazine ([11C]-DTBZ) and [18F]-fluorodopa ([18F]-FDOPA) PET at baseline and 1, 3, 9 and 12 months after the final MPTP injection. Immunohistochemical tyrosine hydroxylase (TH) staining was used to assay nigral TH + area loss post-mortem. The minipigs showed only mild bradykinesia and impaired coordination at early timepoints after MPTP. PET revealed decreases of striatal [11C]-DTBZ and [18F]-FDOPA uptake post-MPTP with a partial spontaneous recovery of [18F]-FDOPA after 9 months. Postmortem histological analysis showed a loss of 71% TH-immunopositive area in the substantia nigra. When testing the efficacy of putative neuroprotective agents, partial spontaneous recovery of dopamine terminal function must be taken into account in the MPTP minipig model of parkinsonism.

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Brazilian minipig as a large-animal model for basic research and stem cell-based tissue engineering. Characterization and in vitro differentiation of bone marrow-derived mesenchymal stem cells

Journal of Applied Oral Science ◽

10.1590/1678-775720130526 ◽

2014 ◽

Vol 22 (3) ◽

pp. 218-227 ◽

Cited By ~ 8

Author(s):

Roberta Targa STRAMANDINOLI-ZANICOTTI ◽

André Lopes CARVALHO ◽

Carmen Lúcia Kuniyoshi REBELATTO ◽

Laurindo Moacir SASSI ◽

Maria Fernanda TORRES ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Marrow ◽

Animal Model ◽

Mesenchymal Stem Cells ◽

Basic Research ◽

Large Animal Model ◽

Large Animal ◽

In Vitro Differentiation

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Collagenase-Induced Patellar Tendinopathy with Neovascularization: First Results towards a Piglet Model of Musculoskeletal Embolization

Biomedicines ◽

10.3390/biomedicines10010002 ◽

2021 ◽

Vol 10 (1) ◽

pp. 2

Author(s):

Julien Ghelfi ◽

Marylène Bacle ◽

Olivier Stephanov ◽

Hélène de Forges ◽

Ian Soulairol ◽

...

Keyword(s):

Animal Model ◽

Histological Analysis ◽

Patellar Tendinopathy ◽

Large Animal Model ◽

Large Animal ◽

Test Results ◽

Collagenase Injection ◽

First Results ◽

Endovascular Approach ◽

New Treatments

Background: Therapeutic strategies targeting neovessels responsible for musculoskeletal chronic pain have emerged, including neovessels embolization. Our study aimed to develop a large animal model of patellar tendinopathy with neovascularization. Methods: Nine 3-month-old male piglets (18 patellar tendons) received percutaneous injections of increasing doses of collagenase (0 to 50 mg) at day 0 (D0). Tendinopathy was evaluated by ultrasound (D7 and D14). Neovascularization was evaluated visually and on angiographies. Bonar score was used for histological analysis (D14). Correlations were evaluated using Spearman’s rank (Rs) test. Results: Research protocol was well tolerated. All tendons were enlarged with a median increase of 31.58% [25–40.28] at D7 (p = 0.244) at D7 and 57.52% [48.41–91.45] at D14 (p = 0.065). Tendons with collagenase injection had more hypoechoic changes, with one tendon rupture (p = 0.012). Neovascularization was reported above 5 mg collagenase (p < 0.01) at D7 and D14 with dose-related neovessels induction (Rs = 0.8, p < 0.001). The Bonar score increased above 5 mg collagenase, correlated with the dose (Rs = 0.666, p = 0.003). Conclusions: The study shows the feasibility, safety and reproducibility of this new large animal model of patellar tendinopathy with neovascularization after collagenase injection. It will allow studying new treatments on direct embolization of neovessels by endovascular approach.

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Large animal models for translational research in acute kidney injury

Renal Failure ◽

10.1080/0886022x.2020.1830108 ◽

2020 ◽

Vol 42 (1) ◽

pp. 1042-1058

Author(s):

Balamurugan Packialakshmi ◽

Ian J. Stewart ◽

David M. Burmeister ◽

Kevin K. Chung ◽

Xiaoming Zhou

Keyword(s):

Acute Kidney Injury ◽

Animal Models ◽

Translational Research ◽

Kidney Injury ◽

Large Animal ◽

Large Animal Models

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Ischaemic conditioning reduces kidney injury in an experimental large-animal model of warm renal ischaemia

British Journal of Surgery ◽

10.1002/bjs.9909 ◽

2015 ◽

Vol 102 (12) ◽

pp. 1517-1525 ◽

Cited By ~ 1

Author(s):

J. P. Hunter ◽

S. A. Hosgood ◽

A. D. Barlow ◽

M. L. Nicholson

Keyword(s):

Animal Model ◽

Kidney Injury ◽

Large Animal Model ◽

Large Animal ◽

Renal Ischaemia ◽

Ischaemic Conditioning

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Safety and Tolerability of the Adeno-Associated Virus Vector, AAV6.2FF, Expressing a Monoclonal Antibody in Murine and Ovine Animal Models

Biomedicines ◽

10.3390/biomedicines9091186 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1186

Author(s):

Amira D. Rghei ◽

Laura P. van Lieshout ◽

Benjamin M. McLeod ◽

Yanlong Pei ◽

Jordyn A. Lopes ◽

...

Keyword(s):

Monoclonal Antibody ◽

Animal Model ◽

Animal Models ◽

Human Monoclonal Antibody ◽

Scale Up ◽

Large Animal Model ◽

Large Animal ◽

Aav Vector ◽

Adeno Associated Virus ◽

Large Animal Models

Adeno-associated virus (AAV) vector mediated expression of therapeutic monoclonal antibodies is an alternative strategy to traditional vaccination to generate immunity in immunosuppressed or immunosenescent individuals. In this study, we vectorized a human monoclonal antibody (31C2) directed against the spike protein of SARS-CoV-2 and determined the safety profile of this AAV vector in mice and sheep as a large animal model. In both studies, plasma biochemical parameters and hematology were comparable to untreated controls. Except for mild myositis at the site of injection, none of the major organs revealed any signs of toxicity. AAV-mediated human IgG expression increased steadily throughout the 28-day study in sheep, resulting in peak concentrations of 21.4–46.7 µg/ mL, demonstrating practical scale up from rodent to large animal models. This alternative approach to immunity is worth further exploration after this demonstration of safety, tolerability, and scalability in a large animal model.

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