Kidney Week

Abstract: FR-OR006

Single-Cell RNA Sequencing of Kidney Tissue, Urine, and Blood of Patients with Immune Checkpoint Inhibitor-Associated Acute Interstitial Nephritis Reveals Conserved T-Cell Populations

Session Information

• Advancing Onconephrology Precision: Biomarkers, Therapeutic Targets, and Patient Outcomes
  October 23, 2026 | Location: Room 401, Convention Center
  Abstract Time: 05:20 PM - 05:30 PM

Category: Onconephrology

• 1600 Onconephrology

Authors

• Mistry, Kavita, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

Kavita Mistry, MD, PhD, FASN

• Kernin, Isabela, Massachusetts General Hospital, Boston, Massachusetts, United States

Isabela Kernin, MS

• Smith, Neal Patrick, Massachusetts General Hospital, Boston, Massachusetts, United States

Neal Patrick Smith

• Best, Roya, Massachusetts General Hospital, Boston, Massachusetts, United States

Roya Best

• Stueber, Christopher T., Massachusetts General Hospital, Boston, Massachusetts, United States

Christopher T. Stueber, MSc

• Tuttle, Elizabeth, Massachusetts General Hospital, Boston, Massachusetts, United States

Elizabeth Tuttle

• Sun, Joie, Massachusetts General Hospital, Boston, Massachusetts, United States

Joie Sun

• Gupta, Shruti, Brigham and Women's Hospital Department of Medicine, Boston, Massachusetts, United States

Shruti Gupta, MD, MPH

• Reynolds, Kerry, Massachusetts General Hospital, Boston, Massachusetts, United States

Kerry Reynolds, MD

• Sise, Meghan E., Massachusetts General Hospital, Boston, Massachusetts, United States

Meghan E. Sise, MD, MS

• Villani, Alexandra-Chloe, Massachusetts General Hospital, Boston, Massachusetts, United States

Alexandra-Chloe Villani, PhD

Background

The use of immune checkpoint inhibitors (ICIs) in cancer treatment is rapidly increasing; however, ICIs can cause immune-related adverse events such as acute interstitial nephritis (ICI-AIN). Diagnosis and treatment of ICI-AIN is limited by incomplete understanding of the underlying immunobiology. We hypothesized that ICI-AIN is driven by the activation and expansion of cytotoxic CD8 tissue resident memory (T_RM) cells that initiate a break of immune tolerance and sustain injury to the renal tubular epithelium, promoting the pathologic recruitment of additional lymphoid, myeloid and antigen-presenting cells, which may also be detectable in urine.

Methods

We used scRNAseq to analyze a total of ~250,000 cells in kidney tissue, blood and urine from a cohort of 25 patients with ICI-AIN, 12 ICI-treated controls with non-AIN AKI, 12 ICI-treated controls with stable kidney function, and 12 ICI-naive patients with stable kidney function.

Results

Our analysis reveals 24 transcriptionally distinct cell subsets, including epithelial cells, CD4 and CD8 T cells, and myeloid cells, with enrichment of urinary T cells in ICI-AIN cases as opposed to controls. Among T cells, there are several subsets, existing on a phenotypic spectrum spanning cytotoxicity (IFNG) to exhaustion (TIGIT), including both T_RM phenotypes (ITGAE) and T cells bearing markers of circulation (KLF2). These cell subsets were conserved across biological compartments.

Conclusion

These findings demonstrate the cellular composition of the inflammatory infiltrate in ICI-AIN. The conservation of immune cell types observed across kidney tissue and urine, and the enrichment of urinary T cells in ICI-AIN, suggest the potential for development of a non-invasive urine-based diagnostic test for ICI-AIN.

Funding

• NIDDK Support