scholarly journals Animal Models of Renal Pathophysiology and Disease

Author(s):  
Adam Hosszu ◽  
Tamas Kaucsar ◽  
Erdmann Seeliger ◽  
Andrea Fekete

AbstractRenal diseases remain devastating illnesses with unacceptably high rates of mortality and morbidity worldwide. Animal models are essential tools to better understand the pathomechanisms of kidney-related illnesses and to develop new, successful therapeutic strategies. Magnetic resonance imaging (MRI) has been actively explored in the last decades for assessing renal function, perfusion, tissue oxygenation as well as the degree of fibrosis and inflammation. This chapter aims to provide a comprehensive overview of animal models of acute and chronic kidney diseases, highlighting MRI-specific considerations, advantages, and pitfalls, and thus assisting the researcher in experiment planning.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.

Author(s):  
Tamas Kaucsar ◽  
Adam Hosszu ◽  
Erdmann Seeliger ◽  
Henning M. Reimann ◽  
Andrea Fekete

AbstractRenal diseases remain devastating illnesses with unacceptably high rates of mortality and morbidity worldwide. Animal models are essential tools to better understand the pathomechanism of kidney-related illnesses and to develop new, successful therapeutic strategies. Magnetic resonance imaging (MRI) has been actively explored in the last decades for assessing renal function, perfusion, tissue oxygenation as well as the degree of fibrosis and inflammation. This chapter aims to provide an overview of the preparation and monitoring of small animals before, during, and after surgical interventions or MR imaging. Standardization of experimental settings such as body temperature or hydration of animals and minimizing pain and distress are essential for diminishing nonexperimental variables as well as for conducting ethical research.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.


Author(s):  
James T. Grist ◽  
Esben Søvsø Hansen ◽  
Frank G. Zöllner ◽  
Christoffer Laustsen

AbstractThe handling of sodium by the renal system is a key indicator of renal function. Alterations in the corticomedullary distribution of sodium are considered important indicators of pathology in renal diseases. The derangement of sodium handling can be noninvasively imaged using sodium magnetic resonance imaging (23Na MRI), with data analysis allowing for the assessment of the corticomedullary sodium gradient. Here we introduce sodium imaging, describe the existing methods, and give an overview of preclinical sodium imaging applications to illustrate the utility and applicability of this technique for measuring renal sodium handling.This chapter 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 chapter is complemented by two separate chapters describing the experimental procedure and data analysis.


Author(s):  
Andreas Pohlmann ◽  
João S. Periquito ◽  
Thoralf Niendorf

AbstractMagnetic resonance imaging (MRI) is an emerging method to obtain valuable functional and structural information about the kidney noninvasively. Before performing specialized MR measurements for probing tissue structure and function, some essential practical steps are needed, which are common for most applications. Here we describe in a step-by-step manner how to (1) achieve the double-oblique slice orientation coronal-to-the-kidney, (2) adapt the scan protocol for avoiding aortic flow artifacts and covering both kidneys, (3) perform localized shimming on the kidney, and (4) check perfusion in the large renal blood vessels using time-of-flight (TOF) angiography. The procedures are tailored to preclinical MRI but conceptionally are also applicable to human MRI.This chapter 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 experimental protocol chapter explains the initial and essential MRI steps that precede specific functional and structural MR imaging techniques (T1- and T2*-mapping, DWI, ASL, etc.), which are described in separate chapters.


Author(s):  
Paula Ramos Delgado ◽  
Ekkehard Küstermann ◽  
André Kühne ◽  
Jason M. Millward ◽  
Thoralf Niendorf ◽  
...  

AbstractMagnetic resonance imaging (MRI) is a noninvasive imaging technology that offers unparalleled anatomical and functional detail, along with diagnostic sensitivity. MRI is suitable for longitudinal studies due to the lack of exposure to ionizing radiation. Before undertaking preclinical MRI investigations of the kidney, the appropriate MRI hardware should be carefully chosen to balance the competing demands of image quality, spatial resolution, and imaging speed, tailored to the specific scientific objectives of the investigation. Here we describe the equipment needed to perform renal MRI in rodents, with the aim to guide the appropriate hardware selection to meet the needs of renal MRI applications.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 chapter on hardware considerations for renal MRI in small animals is complemented by two separate publications describing the experimental procedure and data analysis.


Author(s):  
Kai-Hsiang Chuang ◽  
Frank Kober ◽  
Min-Chi Ku

AbstractThe signal intensity differences measured by an arterial-spin-labelling (ASL) magnetic resonance imaging (MRI) experiment are proportional to the local perfusion, which can be quantified with kinetic modeling. Here we present a step-by-step tutorial for the data post-processing needed to calculate an ASL perfusion map. The process of developing an analysis software is described with the essential program code, which involves nonlinear fitting a tracer kinetic model to the ASL data. Key parameters for the quantification are the arterial transit time (ATT), which is the time the labeled blood takes to flow from the labeling area to the tissue, and the tissue T1. As ATT varies with vasculature, physiology, anesthesia and pathology, it is recommended to measure it using multiple delay times. The tutorial explains how to analyze ASL data with multiple delay times and a T1 map for quantification.This chapter 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 analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Domonkos Pap ◽  
Apor Veres-Székely ◽  
Beáta Szebeni ◽  
Réka Rokonay ◽  
Anna Ónody ◽  
...  

Abstract Background Recently, the role of IL-19, IL-20 and IL-24 has been reported in renal disorders. However, still little is known about their biological role. Methods Localization of IL-20RB was determined in human biopsies and in the kidneys of mice that underwent unilateral ureteral obstruction (UUO). Renal Il19, Il20 and Il24 expression was determined in ischemia/reperfusion, lipopolysaccharide, streptozotocin, or UUO induced animal models of kidney diseases. The effects of H2O2, LPS, TGF-β1, PDGF-B and IL-1β on IL19, IL20 and IL24 expression was determined in peripheral blood mononuclear cells (PBMCs). The extents of extracellular matrix (ECM) and α-SMA, Tgfb1, Pdgfb, and Ctgf expression were determined in the kidneys of Il20rb knockout (KO) and wild type (WT) mice following UUO. The effect of IL-24 was also examined on HK-2 tubular epithelial cells and NRK49F renal fibroblasts. Results IL-20RB was present in the renal biopsies of patients with lupus nephritis, IgA and diabetic nephropathy. Amount of IL-20RB increased in the kidneys of mice underwent UUO. The expression of Il19, Il20 and Il24 increased in the animal models of various kidney diseases. IL-1β, H2O2 and LPS induced the IL19, IL20 and IL24 expression of PBMCs. The extent of ECM, α-SMA, fibronectin, Tgfb1, Pdgfb, and Ctgf expression was lower in the kidney of Il20rb KO compared to WT mice following UUO. IL-24 treatment induced the apoptosis and TGF-β1, PDGF-B, CTGF expression of HK-2 cells. Conclusions Our data confirmed the significance of IL-19, IL-20 and IL-24 in the pathomechanism of renal diseases. Furthermore, we were the first to demonstrate the pro-fibrotic effect of IL-24.


Author(s):  
Kathleen Cantow ◽  
Roger G. Evans ◽  
Dirk Grosenick ◽  
Thomas Gladytz ◽  
Thoralf Niendorf ◽  
...  

AbstractRenal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe basic principles of methodology to quantify renal hemodynamics and tissue oxygenation by means of invasive probes in experimental animals. Advantages and disadvantages of the various methods are discussed in the context of the heterogeneity of renal tissue perfusion and oxygenation.This chapter 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 chapter is complemented by a separate chapter describing the experimental procedure and data analysis.


Author(s):  
Andreas Pohlmann ◽  
Susan J. Back ◽  
Andrea Fekete ◽  
Iris Friedli ◽  
Stefanie Hectors ◽  
...  

AbstractRenal MRI holds incredible promise for making a quantum leap in improving diagnosis and care of patients with a multitude of diseases, by moving beyond the limitations and restrictions of current routine clinical practice. Clinical and preclinical renal MRI is advancing with ever increasing rapidity, and yet, aside from a few examples of renal MRI in routine use, it is still not good enough. Several roadblocks are still delaying the pace of progress, particularly inefficient education of renal MR researchers, and lack of harmonization of approaches that limits the sharing of results among multiple research groups.Here we aim to address these limitations for preclinical renal MRI (predominantly in small animals), by providing a comprehensive collection of more than 40 publications that will serve as a foundational resource for preclinical renal MRI studies. This includes chapters describing the fundamental principles underlying a variety of renal MRI methods, step-by-step protocols for executing renal MRI studies, and detailed guides for data analysis. This collection will serve as a crucial part of a roadmap toward conducting renal MRI studies in a robust and reproducible way, that will promote the standardization and sharing of data.This chapter 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.


Author(s):  
Philippe Garteiser ◽  
Octavia Bane ◽  
Sabrina Doblas ◽  
Iris Friedli ◽  
Stefanie Hectors ◽  
...  

AbstractThe water proton longitudinal relaxation time, T1, is a common and useful MR parameter in nephrology research. Here we provide three step-by-step T1-mapping protocols suitable for different types of nephrology research. Firstly, we provide a single-slice 2D saturation recovery protocol suitable for studies of global pathology, where whole-kidney coverage is unnecessary. Secondly, we provide an inversion recovery type imaging protocol that may be optimized for specific kidney disease applications. Finally, we also provide imaging protocol for small animal kidney imaging in a clinical scanner.This chapter 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 analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.


Author(s):  
Sandra Meyer ◽  
Dieter Fuchs ◽  
Martin Meier

AbstractNoninvasive, robust, and reproducible methods to image kidneys are provided by different imaging modalities. A combination of modalities (multimodality) can give better insight into structure and function and to understand the physiology of the kidney. Magnetic resonance imaging can be complemented by a multimodal imaging approach to obtain additional information or include interventional procedures. In the clinic, renal ultrasound has been essential for the diagnosis and management of kidney disease and for the guidance of invasive procedures for a long time. Adapting ultrasound to preclinical requirements and for translational research, the combination with photoacoustic imaging expands the capabilities to obtain anatomical, functional, and molecular information from animal models. This chapter describes the basic concepts of how to image kidneys using different and most appropriate modalities.This chapter 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 chapter is complemented by two separate chapters describing the experimental procedure and data analysis.


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