Transformative Research in Diabetic Nephropathy 2.0

NCT07444203 | Recruiting DMC

• 1 other identifier: 849580
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diabetic Nephropathies; Kidney Diseases; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2

Keywords

Diabetic nephropathy; Chronic kidney disease; Diabetic kidney disease; Sodium-glucose cotransporter 2 inhibitors; Spatial transcriptomics; Kidney-protective therapy

Outcome Measures

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.

  Baseline enrollment to 18 months.

Secondary Outcomes (6)

• Change in estimated glomerular filtration rate (eGFR)

  Baseline to 18 months

• Change in urine protein/creatinine ratio

  Baseline to 6 months.

• Descriptive histopathology features and spatial gene expression patterns across cohorts

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

• Associations between histopathological features and clinical outcomes

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

• Associations between histopathological features and prior medication exposures

  Baseline (prior/current medication exposure history at enrollment).

Study Arms (4)

Biopsy-confirmed Diabetic Kidney Disease Cohort

Adults with diabetic kidney disease confirmed by a clinically indicated kidney biopsy. This cohort is used to evaluate kidney molecular and histopathologic features in relation to medication exposure history. Interventions/exposures of interest (observational): Primary exposure is sodium-glucose cotransporter 2 inhibitors; additional therapy exposures of interest include renin-angiotensin-aldosterone system blockade, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and other therapies.

Drug: Sodium-glucose cotransporter 2 inhibitors (SGLT2i); Drug: Renin-angiotensin-aldosterone system blockade; Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA); Drug: Mineralocorticoid Receptor Antagonists(MRAs)

Disease Control Kidney Disease Cohort

Adults with other forms of kidney disease (non-DKD), included as disease controls for cross-disease comparisons of molecular and histologic patterns. Interventions/exposures of interest (observational): Medication exposure history is captured to support comparisons across therapy classes, including SGLT2 inhibitors and other disease-modifying therapies.

Drug: Sodium-glucose cotransporter 2 inhibitors (SGLT2i); Drug: Renin-angiotensin-aldosterone system blockade; Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA); Drug: Mineralocorticoid Receptor Antagonists(MRAs)

Living Kidney Donor Cohort

Living kidney donors with available donor biopsy tissue, included as a comparator group to provide reference kidney tissue profiles. Interventions/exposures of interest (observational): Medication exposure history (including kidney-protective therapies where applicable) may be used in descriptive and comparative analyses; donors primarily serve as a reference/control tissue cohort.

Drug: Sodium-glucose cotransporter 2 inhibitors (SGLT2i); Drug: Renin-angiotensin-aldosterone system blockade; Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA); Drug: Mineralocorticoid Receptor Antagonists(MRAs)

Nephrectomy Control Cohort

Adults undergoing nephrectomy with non-tumor, adjacent normal kidney tissue available, included as a control/reference tissue cohort. Interventions/exposures of interest (observational): Medication exposure history (including SGLT2 inhibitors and other kidney-protective therapies) may be incorporated in comparative analyses across cohorts.

Drug: Sodium-glucose cotransporter 2 inhibitors (SGLT2i); Drug: Renin-angiotensin-aldosterone system blockade; Drug: Glucagon-like peptide-1 receptor agonists (GLP 1 RA); Drug: Mineralocorticoid Receptor Antagonists(MRAs)

Interventions

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.

Also known as: SGLT2 inhibitors

Biopsy-confirmed Diabetic Kidney Disease Cohort; Disease Control Kidney Disease Cohort; Living Kidney Donor Cohort; Nephrectomy Control Cohort

Renin-angiotensin-aldosterone system blockade DRUG

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

Biopsy-confirmed Diabetic Kidney Disease Cohort; Disease Control Kidney Disease Cohort; Living Kidney Donor Cohort; Nephrectomy Control Cohort

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

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

Also known as: GLP-1 receptor agonists

Biopsy-confirmed Diabetic Kidney Disease Cohort; Disease Control Kidney Disease Cohort; Living Kidney Donor Cohort; Nephrectomy Control Cohort

Mineralocorticoid Receptor Antagonists(MRAs) DRUG

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

Also known as: MRAs

Biopsy-confirmed Diabetic Kidney Disease Cohort; Disease Control Kidney Disease Cohort; Living Kidney Donor Cohort; Nephrectomy Control Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• GlaxoSmithKline: collaborator
• Boehringer Ingelheim: collaborator
• Regeneron Pharmaceuticals: collaborator
• Novo Nordisk A/S: collaborator
• AstraZeneca: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, Urine, and Kidney tissue specimen.

MeSH Terms

Conditions

Diabetic Nephropathies; Kidney Diseases; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2

Interventions

Sodium-Glucose Transporter 2 Inhibitors; Glucagon-Like Peptide-1 Receptor Agonists; Mineralocorticoid Receptor Antagonists

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents

Study Officials

• Katalin Susztak, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gaia Coppock, MD

CONTACT

2673030158; Gaia.Coppock@pennmedicine.upenn.edu

Mohammed Al Dulaimee, BS

CONTACT

5853589733; mohammed.aldulaimee@pennmedicine.upenn.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: February 24, 2026
• First Posted: March 2, 2026
• Study Start: November 12, 2025
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): November 12, 2028
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1)