Cardiovascular-kidney-metabolic syndrome

Thema:
Efficient drug development

TNO advances preclinical drug development for cardiovascular-kidney-metabolic (CKM) syndrome using a highly translational mouse model that integrates obesity and type 2 diabetes with renal and cardiovascular dysfunction. This diet-induced, hypertension-accelerated KK-Ay mouse model develops progressive GFR decline, albuminuria, cardiac dysfunction and lung damage, recapitulating key features of CKM syndrome. Validated with standard-of-care treatments such as SGLT2 inhibitors and GLP-1 receptor agonists, the model enables robust evaluation of therapeutic efficacy in an integrated model of metabolic, renal and cardiovascular 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

Translational mouse model

The KK-Ay diet-induced hypertension-accelerated mouse model has a backbone of metabolic dysfunction demonstrated by obesity and type 2 diabetes, resulting in diabetic-to-chronic kidney disease and heart failure with preserved ejection fraction.

A characteristic renal feature of this model is the transition from transient hyperfiltration to progressive GFR decline, a clinically relevant feature that is rarely captured in mouse models. This allows studying therapeutic interventions across the early DKD spectrum to progressive CKD within the broader 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 efficacy across organs.

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.

  • In-life phase

    Step 2

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

  • Analysis

    Step 3

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

  • Reporting

    Step 4

    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 CKM research

TNO bridges the gap between preclinical research and clinical outcomes. Our CKM syndrome mouse 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 metabolic, renal and cardiovascular disease
  • Reproducible outcomes enabling confident comparison across studies
  • Careful animal handling and welfare optimisation for robust data generation

Ready to accelerate your CKM research?

Get in touch to explore how TNO’s CKM mouse 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