Acute Kidney Injury (AKI) in cancer patients treated with combo therapies: chemotherapy, or immunotherapy, that is the question

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 acute renal injury (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 management 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 during oncological treatment with pembrolizumab + pemetrexed +/- carboplatin, from 2020 to 2022. We focused on 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 (table 1) was analyzed. AKI stages were identified according to Improving Global Outcomes (KDIGO) guidelines and CTCAE 5.0. Overall, 30 patients (34%) had a non drug-related AKI (90% of which due to pre-renal causes). 43 patients (48%) developed immune-related AKI: sterile pyuria and/or WBC casts 23 pts (53%), other organ IrAEs 35 pts (82%), worsening of renal function upon discontinuation of oncological therapy 32 pts (74%), increase in serum creatinine ≥1 mg/dl between two consecutive pretherapy blood tests 37 pts (86%). 16 patients (18%) had CT nephrotoxicity: Hypo K or Hypo Mg 4 pts (25%), increased urinary electrolytes 7 pts (46%), stable renal function after oncological drugs discontinuation 15 pts (91%), increase in serum creatinine ≤0,5 mg/dl between two consecutive pretherapy blood tests 12 pts (77%). CONCLUSION: One of the main challenges with patients on multiple oncology drug therapy 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 times necessary for the histological analysis. Furthermore, Oncological Guideline recommend to start steroid therapy as soon as the 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 (Image 1).