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Urinary Chemokines in the Diagnosis and Monitoring of Immune Checkpoint Inhibitor-Associated Nephritis
Francisco Gomez-Preciado1,2, Laura Martinez-Valenzuela1, Paula Anton-Pampols3
1Department of Nephrology, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), 08907 Hospitalet de Llobregat, Barcelona, Spain.
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.
Insights
New urinary biomarkers, including CXCL9 and CXCL10, show promise for diagnosing and monitoring acute interstitial nephritis (AIN) caused by immune checkpoint inhibitors (ICIs). These markers aid in assessing kidney function recovery after treatment.
Area of Science:
- Oncology
- Nephrology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) are vital cancer treatments but can cause immune-related adverse events, notably acute interstitial nephritis (ICI-AIN).
- Accurate diagnosis and monitoring of ICI-AIN are crucial for patient management and kidney function preservation.
- Identifying noninvasive biomarkers is essential for early detection and effective follow-up of ICI-AIN.
Purpose of the Study:
- To identify novel urinary biomarkers for diagnosing and monitoring acute interstitial nephritis (AIN) associated with immune checkpoint inhibitors (ICIs).
- To investigate the role of soluble PD-1, PD-L1, PD-L2, chemokines (CXCL5, CXCL9, CXCL10, CXCL11, CCL2, CCL3, CCL5), and cytokines (IL-6, IL-12p70) in ICI-AIN pathogenesis.
- To assess the correlation between biomarker levels and kidney function recovery following treatment.
Main Methods:
- A Luminex assay was used to measure urinary levels of specified biomarkers in patients with ICI-AIN, non-ICI AIN, and acute tubular necrosis (ATN).
- Biomarker concentrations were analyzed at diagnosis and during follow-up in ICI-AIN patients.
- Statistical comparisons were made between patient groups, and correlations with kidney function recovery were assessed.
Main Results:
- Urinary CXCL5, CXCL9, CXCL10, CXCL11, CCL5, and IL-6 were significantly elevated in ICI-AIN patients compared to ATN patients.
- CXCL5, CXCL9, CXCL10, CXCL11, and CCL5 were also higher in ICI-AIN patients versus non-ICI AIN patients.
- Following treatment, CXCL9, CXCL10, CXCL11, and CCL2 levels decreased in ICI-AIN patients, with CXCL9 and CXCL10 reductions correlating with improved kidney function recovery.
Conclusions:
- Urinary CXCL5, CXCL9, CXCL10, CXCL11, CCL5, and IL-6 show potential as noninvasive biomarkers for ICI-AIN.
- Decreased levels of CXCL9, CXCL10, CXCL11, and CCL2 post-treatment indicate their utility in monitoring patient recovery.
- These biomarkers may facilitate precise patient monitoring and improve management strategies for ICI-AIN.
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