Transformative 2.0 for diabetic kidney disease

Transformative Research in Diabetic Nephropathy 2.0: A Proof of Principle Study of SGLT2 Inhibitors (TRIDENT 2.0)

Observational University of Pennsylvania · NCT07444203

This project will try to see if adults with diabetic kidney disease who take SGLT2 diabetes medicines have different biological patterns in archived kidney tissue than similar people who do not take these medicines.

Quick facts

Study typeObservational
Enrollment200 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity of Pennsylvania Academic / other
Locations1 site (Philadelphia, Pennsylvania)
Trial IDNCT07444203 on ClinicalTrials.gov

What this trial studies

TRIDENT 2.0 is a multicenter observational translational effort that uses archived clinical kidney biopsy and surgical tissue to map molecular and histologic features, with a focus on exposure to SGLT2 inhibitors and other kidney-protective therapies. Researchers will transfer one coded slide of formalin-fixed, paraffin-embedded kidney tissue to a central repository and perform spatial transcriptomics and other molecular assays while preserving tissue architecture. Harmonized clinical data, blood and urine samples, and standardized quality-control pipelines will be integrated to relate tissue-level signatures to medication exposure and longitudinal kidney outcomes. The study compares participants who have documented SGLT2 inhibitor exposure with matched participants who do not, without requiring any additional research biopsy.

Who should consider this trial

Good fit: Adults (≥18 years) with diabetic kidney disease or related kidney conditions who are undergoing or have archived clinically indicated kidney biopsy, living-donor biopsy, or nephrectomy and can consent to release one pathology slide and provide clinical data and blood/urine samples are ideal candidates.

Not a fit: People who are not having a clinically indicated biopsy or nephrectomy, cannot consent, or whose archived tissue slides are unavailable or restricted by local policy are not likely to be eligible or to benefit from participation.

Why it matters

Potential benefit: If successful, this work could identify tissue-level signatures linked to SGLT2 use that help explain how these drugs protect kidneys and guide future targeted therapies or biomarkers.

How similar studies have performed: Large randomized trials have shown SGLT2 inhibitors protect kidney function, but applying spatial transcriptomics to link drug exposure to specific tissue signatures is a novel translational approach with limited prior large-scale data.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Age ≥18 years
* eGFR ≥10 ml/min/1.73 m2 based on the 2021 race-free CKD-EPI equation13
* Underwent a clinically indicated kidney biopsy, living donor biopsy, or nephrectomy (non-tumor adjacent tissue available).
* Able and willing to provide informed consent for release of one pathology and clinical data abstraction.

Exclusion Criteria:

* Inability to provide informed consent.
* Archived biopsy or surgical tissue unavailable for slide preparation.
* Any local institutional policy that prohibits release of H\&E slides for research.

Where this trial is running

Philadelphia, Pennsylvania

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Diabetic NephropathiesKidney DiseasesRenal Insufficiency, ChronicDiabetes Mellitus, Type 2Diabetic nephropathyChronic kidney diseaseDiabetic kidney diseaseSodium-glucose cotransporter 2 inhibitors
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.