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Transformative Research in Diabetic Nephropathy 2.0

ConditionsDiabetic NephropathiesKidney DiseasesRenal Insufficiency, ChronicDiabetes Mellitus, Type 2
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity of Pennsylvania

About this trial

The goal of this observational study is to learn more about kidney health in adults with diabetic kidney disease and other groups. Researchers will study kidney tissue and other samples. They want to learn how sodium-glucose cotransporter-2 (SGLT2) inhibitors, a type of diabetes medicine, may affect the kidneys. People can join only if they are already having a kidney biopsy or kidney surgery as part of their regular medical care.

The main questions this study aims to answer are:

* Do people who take SGLT2 inhibitors show different biological patterns in kidney tissue than similar people who do not take them? * Are these kidney tissue patterns linked with how kidney health changes over time?

Researchers will compare participants who take SGLT2 inhibitors with similar participants who do not take these medicines.

Participants will:

Let researchers use one stored slide of kidney tissue from their regular care (no extra research biopsy) Give a blood sample and a urine sample Let researchers review medical record information over time

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial population

TRIDENT 2.0 will enroll approximately 200 participants across multiple sites. Eligible participants include: * Patients with diabetic kidney disease (DKD) confirmed by clinically indicated biopsy. * Patients with other kidney diseases (disease controls). * Living kidney donors (donor biopsy tissue). * Patients undergoing nephrectomy (non-tumor, adjacent normal tissue when available). All participants must provide informed consent for release of one H\&E slide from their clinical biopsy or surgical specimen and for abstraction of relevant clinical data.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i)

    Drug

    Standard-of-care exposure to sodium-glucose cotransporter 2 inhibitors documented from medication history. Participants are not assigned therapy. Exposure status is used for observational comparisons of kidney tissue molecular and histopathologic features.

  • Renin-angiotensin-aldosterone system blockade

    Drug

    Standard-of-care exposure to renin-angiotensin-aldosterone system blockade documented from medication history for observational comparisons.

  • Glucagon-like peptide-1 receptor agonists (GLP 1 RA)

    Drug

    Standard-of-care exposure documented from medication history for observational comparisons.

  • Mineralocorticoid Receptor Antagonists(MRAs)

    Drug

    Standard-of-care exposure documented from medication history for observational comparisons.

Treatment groups

200 Participants
are divided into 4 treatment groups
Group A: Biopsy-confirmed Diabetic Kidney Disease Cohort4 interventions
Group B: Disease Control Kidney Disease Cohort4 interventions
Group C: Living Kidney Donor Cohort4 interventions
Group D: Nephrectomy Control Cohort4 interventions

Trial outcomes

Primary outcomes

1

Change in Kidney Tissue molecular fingerprint

Change/differences in kidney tissue molecular "fingerprint" (molecular pathways / spatial gene expression signatures derived from archived kidney tissue) comparing participants exposed to sodium-glucose cotransporter 2 inhibitors versus controls and participants on other therapies. Tissue profiling includes single-cell spatial transcriptomics with differential expression and pathway analyses stratified by therapy exposure.

Time frame
Baseline enrollment to 18 months.

Secondary outcomes

1

Change in estimated glomerular filtration rate (eGFR)

Change in eGFR calculated using the 2021 race-free CKD-EPI equation.

Time frame
Baseline to 18 months
2

Change in urine protein/creatinine ratio

Change in urine protein/creatinine ratio over follow-up.

Time frame
Baseline to 6 months.
3

Descriptive histopathology features and spatial gene expression patterns across cohorts

Descriptive histopathological features (fibrosis, sclerosis, inflammation, vascular changes) and spatial gene expression patterns evaluated across diabetic kidney disease, disease controls, donor, and nephrectomy cohorts.

Time frame
At enrollment/baseline (Single assessment on the archived clinical specimen slide)
4

Associations between histopathological features and clinical outcomes

Associations between histopathological features and clinical outcomes including eGFR slope, proteinuria, kidney failure, and transplant.

Time frame
Up to 3 years (longitudinal outcome abstraction, including dialysis/transplant/kidney failure/mortality as captured).

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Pennsylvania

Lead sponsor

GlaxoSmithKline

Collaborator

Boehringer Ingelheim

Collaborator

Regeneron Pharmaceuticals

Collaborator

Novo Nordisk A/S

Collaborator

AstraZeneca

Collaborator

Genentech, Inc.

Collaborator

Source ClinicalTrials.gov
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