Abstract
BackgroundImmune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors.MethodsPatients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in serum creatinine of ≥1.5 times the baseline value, based on the Kidney Disease: Improving Global Outcomes criteria. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent renal dysfunction was diagnosed in AKI patients with a final serum creatinine measurement of >1.3 times the baseline value.ResultsAmong 676 patients receiving checkpoint inhibitors, the overall incidence of AKI was 14.2%. Baseline variables independently associated with AKI were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline. AKI was checkpoint inhibitor-associated in one third of all patients with AKI. Checkpoint inhibitor-associated AKI was mostly low-grade, occurred a median of 15 weeks after checkpoint inhibitor initiation, and resulted in persistent renal dysfunction in approximately 40% of the patients. Patients with all-cause AKI had a twofold increased mortality risk, but checkpoint inhibitor-associated AKI was not associated with increased mortality.ConclusionsIn this study, patients receiving checkpoint inhibitors frequently developed AKI due to various etiologies. AKI directly related to the effect of checkpoint inhibitor toxicity did not increase mortality. However, AKI not related to the effect of checkpoint inhibitor toxicity was associated with increased mortality.
Highlights
In the last decade, immune checkpoint inhibition has become an important treatment for patients with a broad range of malignancies, including melanoma, non-small-cell lung carcinoma, urinary tract cancer, and Hodgkin lymphoma [1,2,3,4,5]
Baseline variables independently associated with acute kidney injury (AKI) were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline
AKI was checkpoint inhibitor-associated in one third of all patients with AKI
Summary
Immune checkpoint inhibition has become an important treatment for patients with a broad range of malignancies, including melanoma, non-small-cell lung carcinoma, urinary tract cancer, and Hodgkin lymphoma [1,2,3,4,5]. ICPi blocking programmed cell death protein 1 and programmed death ligand 1 have followed since, and novel agents are currently entering clinical trials [9] Alongside their beneficial effects in patients with cancer, ICPi are known to cause a unique spectrum of autoimmune-related side effects through unrestrained T cell activation. These immune-related adverse events (irAE) may affect multiple organ systems, typically involving the skin, gastrointestinal tract, liver, and endocrine system [10,11]. Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors
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