Abstract: SA-PO1201
Urine mRNA Assay to Measure Compartment-Specific Kidney Injury
Session Information
- CKD: Biomarkers and Emerging Tools for Diagnosis and Monitoring
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Caldato Barsotti, Gabriel, Yale School of Medicine, New Haven, Connecticut, United States
- Kumar, Ashwani, Yale School of Medicine, New Haven, Connecticut, United States
- Yi, Zhengzi, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Pell, John F., Yale School of Medicine, New Haven, Connecticut, United States
- Tanvir, E M, Yale School of Medicine, New Haven, Connecticut, United States
- Moledina, Dennis G., Yale School of Medicine, New Haven, Connecticut, United States
- Luciano, Randy L., Yale School of Medicine, New Haven, Connecticut, United States
- Reghuvaran, Anand, Yale School of Medicine, New Haven, Connecticut, United States
- Meliambro, Kristin, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Perincheri, Sudhir, Yale School of Medicine, New Haven, Connecticut, United States
- Zhang, Weijia, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- He, John Cijiang, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Menon, Madhav C., Yale School of Medicine, New Haven, Connecticut, United States
Background
While kidney biopsy is the diagnostic gold standard, it is invasive. We developed a 10-gene urinary mRNA qPCR assay to reflect histologic injury and predict outcomes
Methods
Urine cell pellet RNA from 54 patients (pre-biopsy, CKD stages 2-5) and 20 healthy controls was analyzed by TaqMan qPCR. Ten genes reflecting glomerular, tubular, inflammatory, and fibrotic injury were chosen for cell-type specificity, injury signals, and presence in urine scRNAseq [Fig-A]. Absolute expression was calculated and normalized to controls. A novel automated digital pathology platform assessed compartment-specific injury.
Results
All 10 transcripts were significantly elevated in urine of patients with any injury vs controls [Fig-B]. Urinary mRNAs selected to reflect cell-specific injury were highly correlated with corresponding compartment specific pathologic features [Table-1]. NPHS1 associated with morphologic normal glomeruli (adjusted for biopsy area), while NPHS2 correlated with glomerulomegaly and increased proteinuria. KIM1 aligned with acute tubular injury score, and VCAM1 correlated with atrophy/fibrosis. Patients were followed for 6 months (n=45). A regression model combining progressive injury markers (VCAM1, SHROOM3) & clinical data (age, eGFR, proteinuria) outperformed clinical data alone in predicting eGFR decline (AUC=0.90 vs 0.78) [C-G]
Conclusion
Our non-invasive, scalable urinary mRNA assay accurately reflects histologic injury and predicts functional decline enabling molecular monitoring of CKD.
Correlation of Digital Pathology and Gene Expression
| Digital Pathology | Gene | Correlation Coefficient | P-Value |
| Normal Glomeruli | NPHS1 | 0.55 | <0.01 |
| Glomerulomegaly | NPHS2 | 0.31 | 0.03 |
| Proteinuria | NPHS2 | 0.35 | <0.01 |
| Normal tubular area | Shroom3 | -0.39 | <0.01 |
| Atrophic tubular number | VCAM1 | 0.44 | <0.01 |
| Interstitial area | VCAM1 | 0.46 | <0.01 |
| Lymphocyte infiltration area | KIM1 | 0.32 | 0.03 |
Funding
- NIDDK Support