Acute kidney injury in patients receiving immune checkpoint inhibitors: a retrospective real-world study.

BACKGROUND: Immune checkpoint inhibitors (ICPi) can cause immune-related adverse events (irAEs) including acute kidney injury (AKI). We investigated the incidence of ICPi-associated AKI (ICPi-AKI) and AKI from other causes (non-ICPi-AKI) in cancer patients treated with ICPi. METHODS: This was a single-centre retrospective cohort study of patients receiving ICPi therapy between December 2011 and August 2020. AKI was defined and staged by the Kidney Disease Improving Global Outcomes creatinine criteria. The primary outcome was the incidence of AKI and ICPi-AKI. RESULTS: A total of 1037 patients were included in the final analysis. The median age was 63 years, 60% were male, and 22% had pre-existing chronic kidney disease. Overall, 189 patients (18.2%) developed AKI of whom 37 patients (3.6%) had ICPi-AKI. In patients with progressive cancer, AKI was not associated with increased mortality. In treatment responders, non-ICPi-AKI was associated with an increased risk of mortality (adjusted hazard ratio [HR] 2.03; 95% confidence interval [CI] 1.12-3.67), whereas ICPi-AKI was not linked to an increased risk of death (adjusted HR 0.60; 95% CI 0.18-1.96). Patients with ICPi-AKI were more likely to have higher AKI stages and less likely to have complete kidney recovery compared with non-ICPi-AKI (54% versus 79%, p = 0.01). CONCLUSION: AKI was common in cancer patients treated with ICPi. Patients with ICPi-AKI had worse kidney outcomes compared to those with AKI from other causes. However, non-ICPi-AKI was associated with a higher risk of death. These findings emphasise the importance of identifying different sub-phenotypes of AKI.

Acute kidney injury in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Acute kidney injury in critically ill cancer patients is associated with mortality: A retrospective analysis.

BACKGROUND: In critically ill patients, acute kidney injury (AKI) is common and associated with short- and long-term complications. Our objectives were to describe the epidemiology and impact of AKI in cancer patients admitted to the Intensive Care Unit (ICU). METHODS: We identified all patients with a haematological malignancy (HM) or solid tumour (ST) who had an emergency admission to the ICU in a tertiary care centre between January 2004 and July 2012. AKI was defined according to the KDIGO criteria. RESULTS: 429 patients were included of whom 259 (60%) had AKI. Among HM patients, 73 (78%) had AKI (70% AKI on admission to ICU; 7% during ICU stay); among ST patients, 186 (56%) had AKI (45% on admission to ICU, 11% during ICU stay). ICU and 28-day mortality rates were 33% and 48%, respectively in HM patients, and 22% and 31%, respectively in ST patients. Multivariable analysis showed that AKI was an independent risk factor for both ICU and 28-day mortality. New AKI after 24 hours in ICU was associated with higher mortality than AKI on admission. CONCLUSIONS: AKI is common in critically ill cancer patients and independently associated with ICU and 28-day mortality.