Related Experiment Video
Updated: Apr 15, 2026
5/6 Nephrectomy Using Sharp Bipolectomy Via Midline Laparotomy in Rats
Published on: April 4, 2025
Translational value of animal models of kidney failure
Alberto Ortiz1, Maria D Sanchez-Niño2, Maria C Izquierdo2
1Nephrology, IIS-Fundacion Jimenez Diaz, Madrid, Spain; REDinREN, Madrid, Spain; Universidad Autonoma de Madrid, Madrid, Spain; IRSIN, Madrid, Spain.
Abstract:
Acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with decreased renal function and increased mortality risk, while the therapeutic armamentarium is unsatisfactory. The availability of adequate animal models may speed up the discovery of biomarkers for disease staging and therapy individualization as well as design and testing of novel therapeutic strategies. Some longstanding animal models have failed to result in therapeutic advances in the clinical setting, such as kidney ischemia-reperfusion injury and diabetic nephropathy models. In this regard, most models for diabetic nephropathy are unsatisfactory in that they do not evolve to renal failure. Satisfactory models for additional nephropathies are needed. These include anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, IgA nephropathy, anti-phospholipase-A2-receptor (PLA2R) membranous nephropathy and Fabry nephropathy. However, recent novel models hold promise for clinical translation. Thus, the AKI to CKD translation has been modeled, in some cases with toxins of interest for human CKD such as aristolochic acid. Genetically modified mice provide models for Alport syndrome evolving to renal failure that have resulted in clinical recommendations, polycystic kidney disease models that have provided clues for the development of tolvaptan, that was recently approved for the human disease in Japan; and animal models also contributed to target C5 with eculizumab in hemolytic uremic syndrome. Some ongoing trials explore novel concepts derived from models, such TWEAK targeting as tissue protection for lupus nephritis. We now review animal models reproducing diverse, genetic and acquired, causes of AKI and CKD evolving to kidney failure and discuss the contribution to clinical translation and prospects for the future.
Insights
Developing better animal models for kidney diseases like acute kidney injury (AKI) and chronic kidney disease (CKD) is crucial for discovering new therapies and biomarkers. Novel models show promise for clinical translation, advancing treatment strategies.
Area of Science:
- Nephrology and Translational Medicine
- Animal Models of Kidney Disease
Background:
- Acute kidney injury (AKI) and chronic kidney disease (CKD) significantly increase mortality, with limited therapeutic options.
- Existing animal models for kidney diseases have often failed to translate into clinical advances.
- There is a critical need for improved animal models that accurately replicate human nephropathies and disease progression.
Purpose of the Study:
- To review diverse animal models that replicate genetic and acquired causes of AKI and CKD.
- To discuss the contribution of these models to clinical translation and therapeutic development.
- To explore future prospects for utilizing animal models in kidney disease research.
Main Methods:
- Review of existing literature on animal models for various kidney diseases, including ischemia-reperfusion injury, diabetic nephropathy, ANCA-associated vasculitis, IgA nephropathy, and others.
- Analysis of genetically modified animal models (e.g., mice) for inherited kidney disorders like Alport syndrome and polycystic kidney disease.
- Examination of novel models for AKI to CKD transition and specific nephropathies, assessing their potential for clinical relevance.
Main Results:
- Traditional models for some kidney diseases have limitations in predicting clinical outcomes.
- Novel models, including those using toxins like aristolochic acid and genetically engineered animals, show promise.
- Specific models have contributed to the development of therapies like tolvaptan for polycystic kidney disease and eculizumab for hemolytic uremic syndrome.
Conclusions:
- Adequate animal models are essential for biomarker discovery, personalized therapy, and testing novel treatments for kidney diseases.
- Recent advancements in animal modeling, particularly genetically modified and toxin-induced models, offer significant potential for clinical translation.
- Continued development and validation of diverse animal models are critical for overcoming therapeutic challenges in AKI and CKD.
