# Urinary Chemokines in the Diagnosis and Monitoring of Immune Checkpoint Inhibitor-Associated Nephritis

## TL;DR

The study explores urinary chemokines as potential noninvasive biomarkers for diagnosing and monitoring immune checkpoint inhibitor-associated nephritis.

## Contribution

The study identifies specific urinary chemokines that are elevated in ICI-AIN and correlate with treatment response and kidney function recovery.

## Key findings

- CXCL5, CXCL9, CXCL10, CXCL11, CCL5, and IL-6 were higher in ICI-AIN compared to ATN.
- CXCL9 and CXCL10 levels decreased after treatment and correlated with improved kidney function recovery.
- These chemokines may serve as noninvasive biomarkers for ICI-AIN diagnosis and monitoring.

## Abstract

Immune checkpoint inhibitors are essential treatments for many oncologic diseases, but with well-known immune-related adverse events, such as acute interstitial nephritis (ICI-AIN). We investigated novel potential biomarkers that could assist in the diagnosis and follow-up of this condition and that are related to the active pathogenic pathways involved. We measured urinary soluble PD-1, PD-L1 and PD-L2, as well as chemokines CXCL5, CXCL9, CXCL10, CXCL11, CCL2, CCL3, CCL5 and cytokines IL-6 and IL-12p70 performing a Luminex assay in urine from patients with ICI-AIN (n = 35) and compared them with patients with AIN from other causes (non-ICI AIN) (n = 29) and ATN (n = 26). We found that CXCL5, CXCL9, CXCL10, CXCL11, CCL5 and IL-6 were higher in patients with ICI-AIN than in those with ATN, and all of them but CXCL9 and IL-6 were also higher in patients with ICI-AIN compared with non-ICI AIN. We also determined these molecules at follow-up for ICI-AIN patients (40 samples from 22 patients) and found that concentrations of CXCL9, CXCL10, CXCL11 and CCL2 decreased after treatment. The decrease of CXCL9 and CXCL10 correlated with greater kidney function recovery at one-year follow-up. These molecules could serve as noninvasive biomarkers and may aid fine patient monitoring.