Immune checkpoint inhibitor-associated AKI varies, often with prolonged delay
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Lower baseline eGFR, use of proton pump inhibitors and extrarenal immune-related adverse events are independent risk factors for AKI in patients treated with immune checkpoint inhibitors, according to data presented at ASN Kidney Week.
Shruti Gupta, MD, MPH, from the department of medicine at Brigham and Women’s Hospital in Boston, presented data of 429 patients who developed immune checkpoint inhibitor-associated AKI (ICPi-AKI) from 30 international sites across 10 countries between 2012 and 2020. The study had 429 patients in a control group who also received immune checkpoint inhibitors, but did not develop ICPi-AKI.
ICPi-AKI occurred at a median of 16 weeks after the initiation of the immune checkpoint inhibitors. However, 10% of patients developed ICPi-AKI more than 1 year after immune checkpoint inhibitor initiation.
“There is a variable and often prolonged delay between ICPi initiation and ICPi-AKI,” Gupta said.
Researchers found 77 patients had stage 1 ICPi-AKI, 144 had stage 2 ICPi-AKI and 208 had stage 3 ICPi-AKI. Urinary findings were highly variable across the cohort, she said.
Extrarenal immune-related adverse events occurred in 243 patients. Rash and hepatis were the most common.
Of the 151 biopsied patients, 125 patients had acute tubulointerstitial nephritis, which was the most common lesion on biopsy. Overall, 30% to 60% of patients with ICPi-AKI had hematuria, proteinuria and pyuria, which was more common in patients with more severe AKI.
Patients who had lower baseline eGFR, used proton pump inhibitors and had prior or concomitant extrarenal immune-related adverse events had a higher risk of ICPi-AKI, she said.
Overall, 276 patients showed renal recovery at a median of 7 weeks after ICPi-AKI. Gupta said 82% of patients were treated with steroids, which were associated with higher adjusted odds of renal recovery, particularly when started within 3 days of ICPi-AKI. Additionally, 121 patients were rechallenged with immune checkpoint inhibitors after an episode of ICPi-AKI and 16.5% developed ICPi-AKI, of which half had renal recovery.
“Renal recovery occurs in two-thirds of patients, with early initiation of steroids associated with greater likelihood of renal recovery,” she said. “Most importantly, fewer than one in five rechallenged patients developed recurrent ICPi-AKI, which shows that rechallenge should be considered in these patients,” she said.
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Gupta S, et al. Paper TH-OR02. Presented at: ASN Kidney Week; Nov. 4-7, 2021 (virtual meeting).
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