Diabetic kidney disease

Thema:
Efficient drug development

TNO advances preclinical drug development for diabetic (DKD) and chronic (CKD) kidney disease using a highly translational mouse model that integrates metabolic, renal and cardiovascular dysfunction. The obese and diabetic phenotype of KK-Ay mice combined with uninephrectomy, metabolic overload and hypertension leads to progressive GFR decline, albuminuria, structural kidney damage and cardiac dysfunction. Validated with standard-of-care treatments such as SGLT2 inhibitors and GLP-1 receptor agonists, this model enables robust evaluation of therapeutic efficacy across disease stages, from early diabetic kidney disease to more advanced chronic kidney disease.

Information

Study types

Preventive & therapeutic efficacy studies

Models

KK-Ay UNx-based CKM syndrome mice

Output

Renal function (GFR), albuminuria, histopathology and transcriptomics data

A translational model to evaluate kidney disease therapies

TNO supports pharmaceutical and biotech partners in evaluating compounds targeting diabetic and chronic kidney disease. Our KK-Ay-based model provides a controlled and reproducible system that recapitulates key clinical features, including hyperfiltration, progressive renal decline and tissue damage.

After introducing L-NNA, the model transitions from early hyperfiltration to sustained GFR decline, enabling assessment of treatment effects across both early and advanced disease stages. This allows benchmarking against standard-of-care therapies and generation of clinically relevant datasets to support decision-making in drug development.

30+

years of preclinical research expertise

200+

completed efficacy studies across disease indications

100+

pharma & biotech partners

Translational model platform

The KK-Ay UNx+HFD+L-NNA model combines metabolic dysfunction with renal disease progression in a single translational framework. Animals develop obesity and type 2 diabetes in combination with albuminuria and structural kidney damage.

A characteristic feature of this model is the transition from transient hyperfiltration to sustained GFR decline, a pattern rarely observed in mouse models but consistently seen in patients. This makes the model particularly suitable for studying therapeutic interventions across the DKD–CKD spectrum and within the broader cardiovascular–kidney–metabolic (CKM) syndrome context. In addition, the model develops a HFpEF-like phenotype, enabling integrated evaluation of cardiac dysfunction alongside metabolic and renal disease.

Use cases

Drug efficacy testing

Evaluate therapeutic interventions in both early DKD and advanced CKD stages.

Mechanism of action studies

Investigate pathways involved in metabolic, renal and cardiovascular dysfunction.

Biomarker & endpoint validation

Assess translational biomarkers such as albuminuria, GFR decline and transcriptomic signatures.

A tailored path to translational insights

  • Study design

    Step 1

    We collaborate to define a study tailored to your compound, research questions, and selected endpoints, ensuring a clear and relevant experimental setup.

  • Model selection

    Step 2

    A study design is tailored to achieve either a DKD-focused or CKD-focused phenotype.

  • In-life phase

    Step 3

    The study is executed with compound administration under controlled conditions, including monitoring of metabolic and renal parameters.

  • Analysis

    Step 4

    Comprehensive analysis including GFR, albuminuria, histology and optional transcriptomics.

  • Reporting

    Step 5

    Results are translated into precise and structured reports, including expert interpretation to support your decision-making and next steps in clinical development.

A reliable partner in translational kidney disease research

TNO bridges the gap between preclinical research and clinical outcomes. Our DKD/CKD model integrates metabolic, renal and cardiovascular dysfunction in a single model, allowing a broader and more realistic assessment of therapeutic efficacy.

  • High translational relevance through clinically representative disease features

  • Integrated disease modeling covering DKD, CKD and CKM syndrome

  • Reproducible outcomes enabling confident comparison across studies

  • Careful animal handling and welfare optimisation for robust data generation

Ready to accelerate your kidney disease research?

Get in touch to explore how TNO’s DKD/CKD model can support your preclinical program.

In an initial discussion, we:

  • align on your research objective
  • define a suitable study design
  • provide a first outline and indicative cost range