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Evaluating Urinary Biomarkers for Early Detection of Kidney Damage in Immune Checkpoint Inhibitors-Treated Patients
Alfredo G Casanova1,2,3, Javier Tascón1,2,3, Edel Del Barco2,4
1Unidad de Toxicología. Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain.
Introduction:
Immune checkpoint inhibitors (ICIs) have improved cancer treatment; however, their use can be limited by immune-mediated adverse events, such as kidney damage. Diagnostic limitations of nephrotoxicity may lead to worsening of the patient's prognosis. This study aimed to validate a panel of urinary biomarkers as diagnostic tools for kidney damage in patients treated with ICIs.
Methods:
A prospective study was conducted on patients scheduled to receive ICIs. Those who subsequently developed kidney damage were considered cases; and those who did not were considered controls. A battery of biomarkers was assessed in urine samples at PRE-1, before the first treatment cycle; PRE-3, before the third cycle; and POST-3, 1 week after the third treatment cycle.
Results:
A total of 46 patients participated in the study. At PRE-1, increased urinary excretion of IGFBP7, NAG, TIMP-2 × IGFBP7, and transferrin was observed in the case group, suggesting that these markers could be useful for early risk stratification of developing kidney damage. Furthermore, increased urinary excretion of albumin and NGAL was observed at PRE-3, suggesting that these markers could be of diagnostic utility to identify patients that could develop kidney damage once treatment is initiated. All of the aforementioned biomarkers demonstrated significant discriminatory ability between cases and controls, as verified by ROC curve analysis.
Conclusion:
The proposed biomarker battery could be used as a preventive tool for decision-making in the management of oncology patients at risk for kidney damage associated with ICIs. Furthermore, its use would allow personalized adjustment of therapy that would minimize the probability of renal complications even before starting the first cycle of treatment.
Insights
Urinary biomarkers can predict kidney damage in patients receiving immune checkpoint inhibitors (ICIs). Early detection using markers like IGFBP7 and TIMP-2 allows for timely intervention to prevent renal complications during cancer treatment.
Area of Science:
- Oncology
- Nephrology
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) offer improved cancer treatment outcomes.
- Nephrotoxicity is a significant immune-mediated adverse event associated with ICIs.
- Current diagnostic limitations for ICI-induced kidney damage can negatively impact patient prognosis.
Purpose of the Study:
- To validate a panel of urinary biomarkers for diagnosing kidney damage in patients undergoing ICI therapy.
- To assess the utility of biomarkers for early risk stratification and diagnosis of nephrotoxicity.
Main Methods:
- Prospective study design involving patients receiving ICIs.
- Categorization of patients into cases (developed kidney damage) and controls (did not).
- Urinary biomarker assessment at pre-treatment (PRE-1), before cycle 3 (PRE-3), and post-treatment (POST-3).
Main Results:
- Increased urinary IGFBP7, NAG, TIMP-2 × IGFBP7, and transferrin at PRE-1 indicated early risk.
- Elevated urinary albumin and NGAL at PRE-3 suggested diagnostic utility for ongoing treatment.
- All assessed biomarkers showed significant discriminatory ability between cases and controls via ROC analysis.
Conclusions:
- A urinary biomarker panel can serve as a preventive tool for managing oncology patients at risk of ICI-related kidney damage.
- Biomarker utilization enables personalized therapy adjustments to minimize renal complications.
- Early detection and intervention can improve outcomes for patients receiving ICIs.
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