How to deal with renal toxicities from immune-based combination treatments in metastatic renal cell carcinoma. A nephrological consultation for Oncologists.

We are witnessing a revolution in the treatment of metastatic renal cell carcinoma (mRCC). Indeed, several immune-based combinations (ICI [immune checkpoint inhibitor] + ICI, or ICI + antiangiogenic agents) have been approved as first-line therapy for mRCC after demonstrating superior efficacy over the previous standard. Despite all the improvements made, safety remains a critical issue, adverse events (AEs) being the main reason for drug discontinuations or dose reductions, ultimately resulting in an increased risk of losing efficacy. Thus, a good understanding of the AEs associated with the use of immune-based combinations, their prevention, and management, are key in order to maximize therapeutic effectiveness. Among these AEs, renal ones are relatively frequent, but always difficult to be diagnosed, not to take into account that it is often difficult to determine which drug is to blame for such toxicities. Chronic kidney disease (CKD) is a common finding in patients with RCC, either as a pre-existing condition and/or as a consequence of cancer and its treatment; furthermore, CKD, especially in advanced stages and in patients undergoing dialysis, may influence the pharmacokinetics and pharmacodynamics properties of anticancer agents. Finally, managing cancer therapy in kidney transplanted patients is another challenge. In this review, we discuss the therapy management of immune-based combinations in patients with CKD, on dialysis, or transplanted, as well as their renal toxicities, with a focus on their prevention, detection and practical management, taking into account the crucial role of the consulting nephrologist within the multidisciplinary care of these patients.

Treatment of acute kidney injury in cancer patients.

Acute kidney injury (AKI), either of pre-renal, renal or post-renal origin, is an important complication in cancer patients, resulting in worse prognosis, withdrawal from effective oncological treatments, longer hospitalizations and increased costs. The aim of this article is to provide a literature review of general and cause-specific treatment strategies for AKI, providing a helpful guide for clinical practice. We propose to classify AKI as patient-related, cancer-related and treatment-related in order to optimize therapeutic interventions. In the setting of patient-related causes, proper assessment of hydration status and avoidance of concomitant nephrotoxic medications is key. Cancer-related causes mainly encompass urinary compression/obstruction, direct tumoural kidney involvement and cancer-induced hypercalcaemia. Rapid recognition and specific treatment can potentially restore renal function. Finally, a pre-treatment comprehensive evaluation of risks and benefits of each treatment should always be performed to identify patients at high risk of treatment-related renal damage and allow the implementation of preventive measures without losing the potentialities of the oncological treatment. Considering the complexity of this field, a multidisciplinary approach is necessary with the goal of reducing the incidence of AKI in cancer patients and improving patient outcomes. The overriding research goal in this area is to gather higher quality data from international collaborative studies.