title: Translational value of animal models of kidney failure.
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.
authors: Nephrology, IIS-Fundacion Jimenez Diaz, Madrid, Spain; REDinREN, Madrid, Spain; Universidad Autonoma de Madrid, Madrid, Spain; IRSIN, Madrid, Spain.
authors: Alberto
authors: A
authors: Ortiz
authors: Nephrology, IIS-Fundacion Jimenez Diaz, Madrid, Spain; REDinREN, Madrid, Spain.
authors: Maria D
authors: MD
authors: Sanchez-Niño
authors: Nephrology, IIS-Fundacion Jimenez Diaz, Madrid, Spain; REDinREN, Madrid, Spain.
authors: Maria C
authors: MC
authors: Izquierdo
authors: Nephrology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
authors: Catalina
authors: C
authors: Martin-Cleary
authors: REDinREN, Madrid, Spain; Dpt. of Pathology, Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS, Madrid, Spain.
authors: Laura
authors: L
authors: Garcia-Bermejo
authors: Nephrology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
authors: Juan A
authors: JA
authors: Moreno
authors: Nephrology, IIS-Fundacion Jimenez Diaz, Madrid, Spain; REDinREN, Madrid, Spain; Universidad Autonoma de Madrid, Madrid, Spain.
authors: Marta
authors: M
authors: Ruiz-Ortega
authors: REDinREN, Madrid, Spain; Nephrology Department, Hospital Universitari de Bellvitge, IDIBELL, L׳Hospitalet de Llobregat, Barcelona, Spain.
authors: Juliana
authors: J
authors: Draibe
authors: REDinREN, Madrid, Spain; Nephrology Department, Hospital Universitari de Bellvitge, IDIBELL, L׳Hospitalet de Llobregat, Barcelona, Spain.
authors: Josep M
authors: JM
authors: Cruzado
authors: REDinREN, Madrid, Spain; Laboratorio de Nefrología, Complexo Hospitalario de Santiago de Compostela (CHUS), Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain.
authors: Miguel A
authors: MA
authors: Garcia-Gonzalez
authors: REDinREN, Madrid, Spain; Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamnca, Spain.
authors: Jose M
authors: JM
authors: Lopez-Novoa
authors: REDinREN, Madrid, Spain; Nephrology Department, Hospital del Mar, Barcelona, Spain.
authors: Maria J
authors: MJ
authors: Soler
authors: Nephrology, IIS-Fundacion Jimenez Diaz, Madrid, Spain; REDinREN, Madrid, Spain. Electronic address: asanz@fjd.es.
authors: Ana B
authors: AB
authors: Sanz
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D006801:Humans; D008957:Models, Genetic; D051437:Renal Insufficiency / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D013045:Species Specificity; D057170:Translational Research, Biomedical / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: Acute kidney injury; Chronic kidney disease; Experimental model; Glomerulonephritis; Hereditary kidney disease; Polycystic kidney disease; Preclinical