#1570 Multicentric study of clinical characteristics and risk factors of acute renal failure in oncological patients under treatment with checkpoint inhibitors

Abstract Background and Aims Acute renal failure (AKI) is a common complication in oncology patients, it limits therapeutic options and can obscure the prognosis. Drugs such as checkpoint inhibitors (ICIs) are being used increasingly in clinical practice, and are not exempt from adverse effects due to their own mechanism of action, as they produce overstimulation of the defense cells, which can cause immune-mediated toxicities. These inflammatory side effects can affect multiple organs, if they affect the kidney, they can cause acute kidney failure. The most common type of clinical-pathological pattern is acute tubulointerstitial nephritis (ATIN). We aim to study the risk factors of AKI in patients receiving ICI treatment. Being able to identify patients with a higher risk of renal failure during treatment may allow us to implement protective measures and carry out a closer surveillance. Method We carried out a multicenter retrospective cohort study including 84 patients participating in the ICITOX study [1], recruited between 2022 and 2024, in the Oncology and Nephrology services of the Clinical Hospital of Salamanca and Clinical Hospital of Valladolid. We defined acute kidney injury according to the guidelines published in 2012. The follow-up time was from the inclusion of the patients by the Oncologist which was the time of prescription of the first cycle of ICI treatment, until 3 months after finishing treatment. The demographic and analytical data of the patients were collected using a spreadsheet computer program and the data were analyzed by statistical study with SPSS program. Results The clinical characteristics of patients with and without AKI are shown in Fig. 1. Compared to controls, the cases had a higher incidence of nephrourological history, with a higher average baseline creatinine in the case group, and the predictive ability of this parameter is shown in Fig. 2. Twenty-eight patients had extrarenal autoimmunity related to ICI administration and it was more prevalent within the AKI patients. Most of the patients included had different types of lung cancer and were being treated with Pembrolizumab. Patients with urinary tract cancer, such as renal carcinoma and urothelial carcinoma, were at higher risk of AKI. The patients in both groups had received approximately the same number of ICI cycles at the time of inclusion in the study. Fourteen patients had already died, the drug was discontinued in 31 patients due to progression, 19 had it stopped due to side effects (12 of them due to AKI suspected to be nephritis secondary to ICIs), 4 patients completed the total number of cycles scheduled by Oncology, and 16 patients were still under treatment. In the cases, AKI occurred on average in cycle 8,7, that is, on average, 17,5 weeks after starting ICI treatment. The patients who developed AKI had received a higher number of drugs that could promote the development of ATIN, including proton pump inhibitors, nonsteroidal anti-inflammatory drugs, antibiotics, diuretics, allopurinol, statins, metamizole, ACE inhibitors/ARBs. Electrolyte imbalances were also studied, finding hypomagnesemia in 29 patients, which was associated with the development of AKI, the predictive ability of this parameter for AKI is shown in Fig. 2. Conclusion In this cohort study, we identified some of the risk factors that predispose patients undergoing treatment with ICI to develop AKI. The main factors involved are baseline creatinine, nephrourological history, type of neoplasia, the use of other drugs that promote ATIN, and hypomagnesemia. Taking these clinical and analytical risk factors into account helps us to be more attentive to certain patients to whom it is advisable to closely monitor renal function, allowing for early detection of AKI. This could help initiate treatment early, minimizing the harmful effects on renal function in patients, which could be crucial for their survival.