TRIDENTTransformative Research
In Diabetic Nephropathy
For clinicians

For physicians: what TRIDENT has learned, and what it means at the bedside

Six findings from TRIDENT tissue with a direct bearing on the care of patients with diabetes and kidney disease, each with its paper.

1
Biopsy in diabetes is safer than its reputationIn 408 research biopsies across 21 sites, any complication occurred in 20 percent (hematoma 15 percent), resource-intense events in 5 percent, and the research core added no significant risk. An 18-gauge needle (OR 0.32 for resource-intense events) and an experienced operator lowered risk; RAS inhibitor use was associated with lower odds of complications. Mohandes et al., CJASN 2026.
2
The RPS classification underperforms in advanced disease; a modification helpsRPS classes 3 and 4 did not differ in kidney survival. Adding a Class 5 defined by visceral epithelial hyperplasia separated risk groups, improved one- and two-year prediction (AUC 0.68 and 0.75) and increased net benefit in decision-curve analysis, with external validation. Mohandes et al., Kidney International 2026.
3
Fibrosis tells you where the patient is; glomerular lesions tell you where they are goingInterstitial fibrosis correlated with eGFR at biopsy, while the rate of decline correlated with global glomerulosclerosis and mesangiolysis, and glomerular epithelial hyperplasia was the strongest predictor of kidney failure. Palmer et al., Kidney International Reports 2021.
4
Non-albuminuric decline is common and realForty to fifty percent of patients with diabetes develop reduced eGFR without preceding albuminuria. A normal urine albumin does not exclude progressive diabetic kidney disease, and such patients are under-represented in trials.
5
A molecular subtype you cannot see on the slideAbout 8 percent of biopsy-confirmed diabetic kidney disease carries B cell-rich immune niches and progresses faster. A plasma panel can identify it; B cell-directed therapy is a testable hypothesis in this subgroup. Dumoulin et al., Nature 2026.
6
When to think about a biopsy in a patient with diabetesRapid eGFR decline, nephrotic-range proteinuria, active urinary sediment, short diabetes duration or absent retinopathy with heavy proteinuria raise the probability of non-diabetic or superimposed disease. TRIDENT data support that the information gained has prognostic value beyond the clinical diagnosis.

References

Mechanism and biomarkers

The science behind these findings

How the kidney fails in diabetes, what the tissue shows, and which blood and urine measurements report it.

Mechanism of progression   Non-invasive biomarkers   Diabetes versus other kidney diseases

Referring a patient

Adults with diabetes who are scheduled for a clinically indicated kidney biopsy at a TRIDENT site can be approached for the study before the procedure. Enrolling sites and investigators are listed on the consortium page; the study team can be reached at TRIDENT@pennmedicine.upenn.edu.