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Abstract: FR-OR004

Longitudinal Biomarker Trends in Immune Checkpoint Inhibitor-Associated Acute Interstitial Nephritis

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Barbarini, Michele, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Mirkheshti, Pouneh, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Cuenca Narvaez, Victor, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Giesen, Callen D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Leung, Nelson, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States
Background

Immune checkpoint inhibitors (ICIs) are associated with a broad range of immune-related adverse events (irAEs), including acute interstitial nephritis (AIN). Current research is focused on identifying noninvasive biomarkers for diagnosis, treatment response, and relapse characterization. The aim of this study was to characterize the longitudinal trends of the main serum and urinary biomarkers during follow-up in patients with ICI-AIN.

Methods

This was a retrospective, single tertiary center study. We enrolled patients clinically diagnosed or with biopsy-proven ICI-AIN between January 2022 and March 2026 with available serum cytokine panel and urinary retinol-binding protein-to-creatinine ratio (RBP/Cr). Laboratories were assessed at the time of AIN diagnosis, during corticosteroid treatment, and after corticosteroid discontinuation (steroid-free period). Outcomes included renal recovery (return of serum creatinine to within 25% of the baseline value).

Results

A total of 46 patients were eligible: 32 with biopsy proven ICI-AIN and 14 clinically confirmed. Serum TNF-α was significantly lower during and after corticosteroid treatment (p = 0.015 and p = 0.043, respectively) compared to AIN onset, as was serum sIL-2Rα (p = 0.006 and p = 0.018, respectively) and urinary RBP/Cr ratio (p = 0.046 and p < 0.001, respectively) (Figure 1a–c); eGFR also significantly increased compared to AIN onset (both p < 0.001), which was further confirmed by eGFR estimates derived from a linear mixed-effects model (Figure 1d–e). In a Cox regression model adjusted for eGFR at AIN onset, a 25% reduction in the RBP/Cr ratio during steroid treatment was associated with renal recovery (HR, 4.97; 95% CI, 1.4–17.7; p = 0.013).

Conclusion

Serum TNF-α, sIL-2Rα, and urinary RBP/Cr significantly decreased over follow-up of patients with ICI-AIN and after steroid treatment, paralleling improvement in kidney function (eGFR), while a 25% reduction in the urinary RBP/Cr was associated with renal recovery. These data support use of these biomarkers as surrogates of disease activity and treatment response in ICI-AIN.