Abstract
Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have unprecedentedly improved global prognosis in several types of cancers. However, they are associated with the occurrence of immune-related adverse events. Despite their low incidence, renal complications can interfere with the oncologic strategy. The breaking of peripheral tolerance and the emergence of auto- or drug-reactive T-cells are the main pathophysiological hypotheses to explain renal complications after ICI exposure. ICIs can induce a large spectrum of renal symptoms with variable severity (from isolated electrolyte disorders to dialysis-dependent acute kidney injury (AKI)) and presentation (acute tubule-interstitial nephritis in >90% of cases and a minority of glomerular diseases). In this review, the current trends in diagnosis and treatment strategies are summarized. The diagnosis of ICI-related renal complications requires special steps to avoid confounding factors, identify known risk factors (lower baseline estimated glomerular filtration rate, proton pump inhibitor use, and combination ICI therapy), and prove ICI causality, even after long-term exposure (weeks to months). A kidney biopsy should be performed as soon as possible. The treatment strategies rely on ICI discontinuation as well as co-medications, corticosteroids for 2 months, and tailored immunosuppressive drugs when renal response is not achieved.
Highlights
Immune checkpoint inhibitors (ICIs) have been approved in the field of oncology, providing an original antitumor approach compared to chemotherapies
This review focuses on diagnostic and therapeutic strategies for ICI-related renal complications
The clinician should be able to determine whether the patient suffers from pre-renal, post-renal, or intrinsic acute kidney injury (AKI) and which renal compartment is involved in the ICI toxicity
Summary
Immune checkpoint inhibitors (ICIs) have been approved in the field of oncology, providing an original antitumor approach compared to chemotherapies. A combination of the anti-CTLA4 tremelimumab and the anti-PDL1 durvalumab is promising in advanced non-small cell lung cancer [2], head and neck squamous cell carcinoma [3], and other solid tumors such as advanced hepatocellular carcinoma [4]. Type of Indications melanoma, renal cell carcinoma, CRC mesothelioma, in combination with durvalumab in advanced non-small cell lung cancer, head and neck squamous cell carcinoma, advanced hepatocellular carcinoma anti-PD1. CRC: colorectal cancer; NSCLC: Non-small-cell lung carcinoma; SCLC: Small-cell lung carcinoma While therapy with this class of agents has resulted in improved clinical outcomes for patients with multiple tumor types, a broad spectrum of irAEs may affect any organ system, with variable clinical presentations
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