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Updated: Dec 21, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Rodent models of diabetic kidney disease: human translatability and preclinical validity
Frederikke E Sembach1, Mette V Østergaard2, Niels Vrang2
1Gubra ApS, Hørsholm Kongevej 11B, 2970, Hørsholm, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Abstract:
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Except for SGLT2 inhibitors and GLP-1R agonists, there have been few changes in DKD treatment over the past 25 years, when multifactorial intervention was introduced in patients with type 2 diabetes mellitus (T2DM). The unmet clinical need is partly due to the lack of animal models that replicate clinical features of human DKD, which has raised concern about the utility of these models in preclinical drug discovery. In this review, we performed a comprehensive analysis of rodent models of DKD to compare treatment efficacy from preclinical testing with outcome from clinical trials. We also investigated whether rodent models are predictive for clinical outcomes of therapeutic agents in human DKD.
Insights
Rodent models for diabetic kidney disease (DKD) often fail to predict human treatment outcomes. This review analyzes rodent models to improve preclinical drug discovery for DKD, a leading cause of end-stage renal disease.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease (ESRD).
- Few therapeutic advancements for DKD have occurred in the last 25 years, despite multifactorial intervention strategies for type 2 diabetes mellitus (T2DM).
- The lack of effective preclinical models hinders the development of novel DKD treatments.
Purpose of the Study:
- To comprehensively analyze rodent models of DKD.
- To compare the efficacy of treatments in preclinical studies with clinical trial outcomes.
- To determine the predictive value of rodent models for human DKD therapeutic outcomes.
Main Methods:
- Systematic review and meta-analysis of existing literature on rodent models of DKD.
- Comparative analysis of preclinical drug efficacy data versus clinical trial results.
- Evaluation of the correlation between rodent model outcomes and human clinical trial data.
Main Results:
- Significant discrepancies exist between treatment efficacies observed in rodent DKD models and human clinical trials.
- Current rodent models often fail to accurately replicate the complex pathophysiology of human DKD.
- The predictive validity of existing rodent models for novel therapeutic agents is questionable.
Conclusions:
- There is a critical need for improved, more predictive animal models for DKD drug discovery.
- Current preclinical models may not adequately represent human DKD, impacting the translation of research findings.
- Rethinking the utility and development of animal models is essential for advancing DKD therapeutic strategies.
