ASNRT — Arab Society of Nephrology and Renal Transplantation

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Acute kidney injury in patients treated with immune checkpoint inhibitors

In a large international cohort, immune checkpoint inhibitor-associated acute kidney injury most often presented as acute tubulointerstitial nephritis, with renal recovery in about two-thirds of patients and improved recovery when corticosteroids were started early.

Background

Immune checkpoint inhibitors (ICPis) have transformed cancer therapy, but their use is accompanied by immune-related adverse events that can affect virtually any organ, including the kidney. ICPi-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity, prompting efforts to define its predictors, pathology, and optimal management.

Study design

Investigators collected data on 429 patients with ICPi-AKI and 429 contemporaneous control patients who received ICPis without developing AKI, drawn from 30 sites across 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery, and a multivariable Cox model estimated the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.

Key findings

ICPi-AKI occurred at a median of 16 weeks after ICPi initiation, and acute tubulointerstitial nephritis was the dominant lesion, seen in 125 of 151 biopsied patients (82.7%). Lower baseline eGFR, proton pump inhibitor use, and extrarenal immune-related adverse events were each associated with higher risk. Renal recovery occurred in 64.3% of patients, and corticosteroid treatment within 14 days, particularly within 3 days, was associated with higher odds of recovery; of 121 patients rechallenged, 16.5% developed recurrent ICPi-AKI, with no survival difference between those rechallenged and those not.

Clinical implications

These findings support prompt recognition of ICPi-AKI, consideration of kidney biopsy to confirm tubulointerstitial nephritis, and early initiation of corticosteroids to improve renal recovery. Risk awareness for patients with reduced baseline renal function, PPI use, or extrarenal toxicities, along with case-by-case multidisciplinary decisions about ICPi rechallenge, can help balance oncologic benefit against renal risk.

Category

Research

Source

Journal for ImmunoTherapy of Cancer

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