3789 SERUM AND URINARY SOLUBLE PD-1, PD-L1 AND PD-L2 AS BIOMARKERS FOR CHECKPOINT INHIBITOR RELATED ACUTE INTERSTITIAL NEPHRITIS

Abstract Background and Aims Acute interstitial nephritis (AIN) related to Immune Checkpoint Inhibitors (ICI) is a frequently described adverse effect, although the mechanisms are not fully understood. The gold standard for the diagnosis is kidney biopsy. Although it is invasive, it is necessary as AIN can be confounded with other causes of acute kidney injury (AKI) in oncologic patients. The diagnosis of AIN has therapeutical consequences such as the need to withdraw the drug if confirmed, possibly diminishing patients’ life expectancy. Few biomarkers have been proposed for non-invasive diagnosis or the follow-up of these patients, which could be useful when the biopsy is contraindicated or not available. Our aim was to study the Immune Checkpoint pathway during the event, as well as analyse potential biomarkers directly related to the pathway. Method We performed an observational study. We recruited patients with incident diagnosis of AIN related to ICI in our institution from 2018 to 2022. We obtained serum and urine at the time of diagnosis after signing informed consent. We recruited n = 18 patients with the diagnosis of AIN related to ICI. For comparison, we recruited patients with non ICI-related AIN (n = 18), patients with active ANCA-vasculitis (n = 35), patients with acute tubular necrosis (ATN) (n = 22), and controls (n = 36) (patients with diagnosis of malignancy without AKI (n = 22), and healthy controls (n = 14)). We determined soluble PD-1 (sPD-1), sPD-L1 and sPD-L2 in serum and urine using a multiplex bead-based Luminex assay. Besides, we performed PD-L1 immunohistochemistry and PD-L2 immunofluorescence staining of kidney biopsies from patients with ICI-related AIN (n = 14) and compared to patients with non ICI-related AIN (n = 10). Results Serum sPD-1 was higher in patients with AIN compared to controls (p = 0.0004) and patients with ATN (p = 0.021). There were no differences between controls and ATN (p = 0.76). Urinary sPD-1 was lower in subjects with AKI compared to controls (control vs AIN (p = 0.019), control vs active vasculitis (p