Acute kidney injury in patients treated with immune checkpoint inhibitors

Abstract

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

Safety of Immune Checkpoint Inhibitor Resumption after Interruption for Immune-Related Adverse Events, a Narrative Review

“…Finally, a total of 1563 patients from 18 studies received ICI resumption after ICI discontinuation due to irAEs. After the exclusion of the studies without details on the grade of initial irAEs or those including only patients with grade ≥3 irAEs [ 21 , 35 , 38 , 39 ], 47% (33.0–55.0) of the remaining patients with ICI resumption had grade ≥3 initial irAEs. As mentioned above, all irAEs occurring after ICI resumption were considered as second irAE.…”

“…Most are multicentric, except for four studies [ 30 , 39 , 40 , 42 ]. Only four studies contained data of more than 100 patients with ICI resumption [ 21 , 32 , 33 , 38 ].…”

“…Aside from heterogeneity in the timing range of ICI resumption ( Table 1 ), the studies were heterogeneous in terms of malignancy type and ICI regimen. Moreover, different studies assessed the safety of ICI resumption through the perspective of cancer type (i.e., renal cell carcinoma, melanoma, non-small-cell lung cancer) [ 31 , 34 , 37 , 39 , 40 , 41 , 42 , 44 , 46 ], irAE type (i.e., acute kidney injury, immune-mediated diarrhea and colitis (IMDC)) [ 32 , 35 , 38 ] or both [ 21 , 29 , 30 , 33 , 36 , 43 ].…”

Molecular Mechanisms and Biomarkers Associated with Chemotherapy-Induced AKI

“…Most surgical patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are admitted to the ICU and frequently develop severe AKI [ 46 , 47 ]. Immune checkpoint inhibitors (ICPi), which is one of the most frequently prescribed anticancer treatments nowadays [ 48 ], are associated with a unique spectrum of immune-related adverse events affecting several organs, including the kidneys [ 49 ]. Direct renal toxicity of these drugs can have severe consequences and lead to ICU admission.…”

“…ICPi-induced AKI is being observed with increasing frequency in patients. In the largest retrospective study available, AKI occurred at a median time of 16 weeks (IQR 8–32) following ICPi initiation [ 49 ]. When a kidney biopsy was performed, the typical lesion associated with AKI was acute tubulointerstitial nephritis (ATIN) [ 49 ].…”