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

Polydimethylsiloxanes with Grafted Dibenzoylmethanatoboron Difluoride: Synthesis and Properties

A method for the preparation of polydimethylsiloxanes with grafted methoxy-substituted dibenzoylmethanatoboron difluoride has been described. The structures of prepared polymers were confirmed using NMR, IR spectroscopy and gel permeation chromatography methods. Their thermal properties were investigated using thermal gravimetric analysis, differential scanning calorimetry and thermomechanical analysis. The prepared polymers had good thermal (Td5% up to 393 °C) and thermo-oxidative (Td5% = 413 °C) stability. The polymers started to transit in a viscous flow state at about 40 °C (for 3 a) and at about 20 °C (for 3 b). The viscoelastic characteristics of prepared polymers were determined in the sinusoidal oscillating vibrations mode. It was shown that the studied polymers at low frequencies at room temperature are viscoelastic fluids (G′ < G″). Increasing the frequency led to inversion (crossover) of dependences G′ and G″, which indicated the transition of polymers from viscous to elastomeric behavior characteristics, and the beginning of the formation of a physical network. Optical properties were studied using electron absorption, steady-state and time-resolved fluorescence spectroscopy. It was shown that intramolecular H-dimers exist in the ground state. The polymers studied had a bright fluorescence in the solution and in the solid state, consisting of bands of monomer and excimer emission. Thermally-activated delayed fluorescence was observed in the solution and the solid state. The prepared polymers possess intriguing properties that make them useful as optical materials, sensors or imaging agents

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 ICPiAKI.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 patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. 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. 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. 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