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Toxins
Special Issues
Analysis and Applications of Uremic Animal Models
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Analysis and Applications of Uremic Animal Models

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: closed (1 December 2022) | Viewed by 5198

Special Issue Editors

Prof. Dr. Karin G.F. Gerritsen

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Guest Editor
Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands
Interests: home dialysis; artificial kidney; sorbent dialysis; portable dialysis; uremic large animal models; uremic toxins
Prof. Dr. Jaap A. Joles

E-Mail Website
Guest Editor
Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands
Interests: cardiorenal syndrome; uremic animal models; regenerative nephrology; renal hypoxia; gasotransmitters; developmental renal programming; diabetic kidney disease; portable dialysis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Uremic animal models are crucial for biomedical research into acute and chronic kidney disease as an intermediate between in vitro studies and human trials, since they may offer valuable information about pathophysiological mechanisms and are indispensable for assessing the efficacy and safety of novel drugs, biomaterials, and medical devices for kidney disease. Selecting a suitable model is essential to obtain data that can be extrapolated to the human situation. While mouse models are pivotal for genetically engineered models for elucidating gene function in kidney failure, large uremic animal models are required for preclinical testing of novel dialysis technologies. For the selection of the best model, it is important to be aware of the possibilities, challenges, and limitations of the various small and large uremic animal models, the strategies for inducing acute or chronic uremia (by invasive procedures (surgical ablation, vascular or ureteral ligation, radiographic embolization) or non-invasive methods (drugs, genetic models)), the characteristics of induced kidney failure (glomerular or tubulointerstitial injury or just reduction in the number of nephrons), and the resulting uremic plasma profile. The aim of this Special Issue is to offer a platform, both for clinicians and basic researchers, to present and discuss novel aspects of uremic animal models. We do hope that all published papers will significantly improve knowledge on uremic animal models and will help in selecting the best model for a certain purpose which will contribute to replacement, reduction, and refinement in animal use.

Prof. Dr. Karin G.F. Gerritsen
Prof. Dr. Jaap A. Joles
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • uremic animal model
  • experimental chronic kidney disease
  • in vivo models
  • translational nephrology

Published Papers (2 papers)

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Research

13 pages, 3810 KiB  
Article
Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers
by Jarrett Moyer, Mark W. Wilson, Thomas A. Sorrentino, Ana Santandreu, Caressa Chen, Dean Hu, Amy Kerdok, Edward Porock, Nathan Wright, Jimmy Ly, Charles Blaha, Lynda A. Frassetto, William H. Fissell, Shant M. Vartanian and Shuvo Roy
Toxins 2023, 15(9), 547; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins15090547 - 04 Sep 2023
Viewed by 2437
Abstract
Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to [...] Read more.
Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76–105 mL/min/m2 and 140–165 mL/min/m2, respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices. Full article
(This article belongs to the Special Issue Analysis and Applications of Uremic Animal Models)
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18 pages, 5014 KiB  
Article
A Uremic Pig Model for Peritoneal Dialysis
by Joost C. de Vries, Maaike K. van Gelder, Anneke S. Monninkhof, Sabbir Ahmed, Diënty H. M. Hazenbrink, Tri Q. Nguyen, Gèrard A. P. de Kort, Evert-Jan P. A. Vonken, Koen R. D. Vaessen, Jaap A. Joles, Marianne C. Verhaar and Karin G. F. Gerritsen
Toxins 2022, 14(9), 635; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins14090635 - 14 Sep 2022
Cited by 3 | Viewed by 2157
Abstract
With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a porcine model with kidney failure. Stable chronic kidney injury was induced by [...] Read more.
With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a porcine model with kidney failure. Stable chronic kidney injury was induced by bilateral subtotal renal artery embolization. Before applying PD, temporary aggravation of uremia was induced by administration of gentamicin (10 mg/kg i.v. twice daily for 7 days), to obtain uremic solute levels within the range of those of dialysis patients. Peritoneal transport was assessed using a standard peritoneal permeability assessment (SPA). After embolization, urea and creatinine concentrations transiently increased from 1.6 ± 0.3 to 7.5 ± 1.2 mM and from 103 ± 14 to 338 ± 67 µM, respectively, followed by stabilization within 1–2 weeks to 2.5 ± 1.1 mM and 174 ± 28 µM, respectively. Gentamicin induced temporary acute-on-chronic kidney injury with peak urea and creatinine concentrations of 16.7 ± 5.3 mM and 932 ± 470 µM respectively. PD was successfully applied, although frequently complicated by peritonitis. SPA showed a low transport status (D/P creatinine at 4 h of 0.41 (0.36–0.53)) with a mass transfer area coefficient of 9.6 ± 3.1, 4.6 ± 2.6, 3.4 ± 2.3 mL/min for urea, creatinine, and phosphate respectively. In conclusion, this porcine model with on-demand aggravation of uremia is suitable for PD albeit with peritoneal transport characterized by a low transport status. Full article
(This article belongs to the Special Issue Analysis and Applications of Uremic Animal Models)
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