TRIDENT

• Goals of TRIDENT

Goals of TRIDENT

The overarching goal of TRIDENT is to establish a tissue-anchored, longitudinal research framework that enables precise classification of diabetic kidney disease, identification of disease-driving mechanisms, and acceleration of biomarker and therapeutic development.

1. Establish a biopsy-anchored observational cohort

Diabetic kidney disease is typically diagnosed using clinical criteria, yet disease course is highly heterogeneous. Some patients experience stable kidney function for years, while others progress rapidly to kidney failure.

TRIDENT establishes a prospective, multi-center observational cohort of adults with diabetes undergoing clinically indicated kidney biopsy. By enrolling patients with biopsy-confirmed diabetic kidney disease and following them longitudinally, TRIDENT enables rigorous characterization of kidney function trajectories and direct linkage between kidney tissue pathology and clinical outcomes.

2. Define genetic, epigenetic, and molecular contributors to disease progression

Diabetic kidney disease shows familial clustering, yet the genetic and molecular factors underlying susceptibility, progression rate, and biological heterogeneity remain incompletely understood.

TRIDENT integrates germline genetic analyses, including whole-exome sequencing, with epigenomic profiling and comprehensive molecular characterization of kidney tissue. These analyses are complemented by bulk and single-cell transcriptomics, long-read sequencing, proteomics, and metabolomics, enabling multi-layered investigation of disease mechanisms across cell types and molecular pathways.

3. Enable cell-type–resolved and spatially informed mechanistic discovery

Bulk tissue measurements obscure the cellular and spatial heterogeneity that underlies diabetic kidney disease.

TRIDENT applies single-cell and spatially resolved transcriptomic technologies to human kidney biopsies to define cell-type–specific and niche-specific injury programs. By integrating spatial single-cell data with histopathology and molecular profiling, TRIDENT aims to identify pathogenic cell states, intercellular interactions, and microenvironmental features that drive disease progression.

4. Accelerate therapeutic target identification and biomarker development

Despite the global burden of diabetic kidney disease, therapeutic development has been limited in part by restricted access to human kidney tissue linked to outcomes and molecular phenotypes.

By combining kidney biopsy pathology with multi-omic profiling—including genomics, transcriptomics, proteomics, metabolomics, and spatial single-cell data—TRIDENT aims to identify core disease-driving pathways directly in human tissue. These insights are intended to inform mechanism-based therapeutic strategies and prioritize targets with direct relevance to human disease.

5. Discover and validate tissue-informed biomarkers

Reliable diagnostic and prognostic biomarkers for diabetic kidney disease remain limited, constraining risk stratification and therapeutic decision-making.

TRIDENT leverages paired kidney tissue, blood, and urine samples to discover and validate biomarkers that reflect underlying tissue biology. These efforts support the development of non-invasive markers for diagnosis, prognosis, patient stratification, and monitoring of therapeutic response.

6. Enable patient stratification and future clinical trials

Single-center studies are often underpowered to address the biological and clinical heterogeneity of diabetic kidney disease.

TRIDENT functions as a coordinated, multi-institutional consortium of academic investigators and industry partners, creating a scalable platform for biologically informed patient stratification, biomarker-driven trial design, and efficient translation of discoveries into future clinical studies.