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.

Prevention of Cardiac Surgery-Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial.

BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

Tissue oxygen saturation changes and postoperative complications in cardiac surgery: a prospective observational study.

BACKGROUND: Cardiac surgery with extracorporeal circulation (ECC) can induce microvascular dysfunction and tissue hypoperfusion. We hypothesized that the alterations in near-infrared spectroscopy (NIRS)-derived parameters would be associated with post-operative complications in cardiac surgery patients. METHODS: Prospective observational study performed at two University Hospitals. Ninety patients undergoing cardiac surgery with ECC were enrolled. The NIRS sensor was applied on the thenar eminence. A vascular occlusion test (VOT, 3-min ischemia) was performed at baseline (t0), at Intensive Care Unit (ICU) admission (t1), 3 (t2) and 6 (t3) hours later. Baseline tissue oxygen saturation (StO2), oxygen extraction rate and microvascular reactivity indices were calculated. RESULTS: In the first hours after cardiac surgery, StO2 tended to increase (86% [80-89] at T3 versus 82% [79-86] at T0, p = ns), while both tissue oxygen extraction and microvascular reactivity tended to decrease, as indicated by increasing occlusion slope (- 8.1%/min [- 11.2 to - 7] at T3 versus - 11.2%/min [- 13.9 to - 7.9] at T0, p = ns) and decreasing recovery slope (1.9%/sec [1.1-2.9] at T3 versus 3.1%/sec [2.3-3.9] at T0, p = ns). No substantial differences were found in NIRS-derived variables and their changes over time between patients with complications and those without complications. CONCLUSIONS: Peripheral tissue oxygen extraction and microvascular reactivity were reduced during the first hours after cardiac surgery. NIRS-derived parameters were not able to predict complications in this population of cardiac surgery patients.