#3652 ACUTE KIDNEY INJURY (AKI) IN CANCER PATIENTS TREATED WITH COMBO THERAPIES: CHEMOTHERAPY, OR IMMUNOTHERAPY, THAT IS THE QUESTION
Authors: Pirovano Marta , Sartò Giulia Vanessa Re , La Verde Nicla , Bramati Annalisa , Cosmai Laura , Gallieni Maurizio 
Published: June 2023

Abstract

Background and Aims
Lung cancer is the second most common malignancy in men and the third in women and approximately 85% of all cases are constituted by non-small cell carcinoma (NSCLC). In recent years, the introduction of immune checkpoint inhibitors and molecular targeted therapies, as monotherapy or in association with chemotherapy, has revolutionized the treatment of NSCLS. Pembrolizumab in association with pemetrexed and carboplatin, for instance, has been approved as first-line treatment for non-squamous NSCLC. Nephrotoxic side effects of both old and new therapies continue to be a substantial adverse event (AE) and could preclude effective oncological treatment. When a patient in combined oncological therapy develops AKI it is not always easy to establish which drug is responsible of the AE. The objective of our study was to develop a diagnostic algorithm to help the clinician to diagnose and manage AKI in patient treated with pembrolizumab + pemetrexed +/- carboplatin.

Method
We performed a retrospective multicentric data collection. We analyzed data about all the patient referred to the onconephrology outpatient clinic due to AKI (Stage 2 or higher) during oncological treatment with pembrolizumab + pemetrexed +/- carboplatin, from 2020 to 2022.
AKI stages were identified according to KDIGO guidelines and CTCAE 5.0.
We focused on the following data: chemical-physical urinalysis, urinary electrolytes, serum electrolytes, kidney function (AKI progression and trend of renal function after oncological drug discontinuation).

Results
A cohort of 89 patients was analyzed: 54 males (61%) and 35 females (39%), with an average age of 69 years (51-76). The main comorbidities were hypertension (76%), diabetes mellitus (36%), CKD (64%) and cardiovascular diseases (26%). Overall, 11 patients (12%) had a non drug-related AKI, 90% of which due to pre-renal causes. 43 patients developed immune-related AKI; among these 23 pts had sterile pyuria and/or WBC casts, 35 pts had other organ IrAEs, 32 pts had AKI progression upon discontinuation of oncological therapy, and 37 pts had an increase in serum creatinine ≥1 mg/dl between two consecutive pretherapy blood tests. Chemotherapy-induced nephrotoxicity occurred in 35 patients and had the following features: hypo K or hypo Mg in 9 pts, increased urinary electrolytes in 16 pts, stable renal function after oncological drugs discontinuation in 32 pts and an increase in serum creatinine ≤0,5 mg/dl between two consecutive pretherapy blood tests in 27 pts. Characteristics of drug-related AKI are summarized in Table 1.

Conclusion
One of the main challenges with patients on multiple cancer therapies who develop AKI is to identify the possible drug responsible for the nephrotoxicity to avoid unnecessary suspension of one or more oncological drugs. Although the most frequently suggested approach is the execution of the renal biopsy, it is not always possible to perform it in a short time due to difficulties in organizing the diagnostic procedure and the time necessary for the histological analysis. Furthermore, Oncological Guideline recommend starting steroid therapy as soon as the Grade ≥2 immune related AEs develop. The above retrospective results shed light on the main characteristic of AKI due to immunotherapy or chemotherapy; the information obtained helped us to develop a diagnostic algorithm that addresses the clinician in identifying with reasonable certainty the cause of AKI without the need to perform a renal biopsy (Figure 1).