Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor-Associated Acute Kidney Injury: CON.

Abstract

Immune checkpoint inhibitors (ICPis) have revolutionized the treatment of cancers by engaging the patient’s own immune system against the tumor (1⇓–3). Checkpoint pathways are innate mechanisms to put the brakes on immune activation. Approved agents target checkpoint pathways mediated by cytotoxic T lymphocyte–associated antigen 4 (CTLA4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PDL-1) (1,4⇓⇓–7). Releasing the breaks on the immune system enhances destruction of tumor cells, but can lead to immune-related adverse effects (8,9), including renal toxicity (1,2,10⇓⇓–13). The incidence of renal toxicity with ICPis ranges from 1% to 5% (12). This risk is higher in patients that are on combination therapy with both anti-CTLA4 and anti–PD-1/PD-L1 with an odds ratio of 3.88 (95% CI, 2.21 to 6.81) (14). Further, a lower baseline GFR before therapy increases risk of kidney injury with an odds ratio of 1.99 (95% CI, 1.43 to 2.76) for every 30 ml/min per 1.73 m2 decline (14). The time to prevent kidney injury starts at the time of ICPi initiation. Based on a recent multicenter review of 138 patients, risk of ICPi-associated AKI (ICPi-AKI) was higher with concomitant use of proton pump inhibitors (PPIs) with an odds ratio of 2.85 (95% CI, 1.81 to 4.48) (14). Cortazar et al. describe that 70% of patients with ICPi-AKI were on potential acute interstitial nephritis (AIN)–causing medications including PPIs (15,16), nonsteroidal anti-inflammatory drugs (NSAIDs) (17), and antibiotics (18) where PPI was present on >50% of patients’ medication lists. Baseline use of PPIs was also associated with ICPi-AKI in a large study by Seethapathy et al. (1), particularly 2.5 months after being on ICPi. Appropriate counseling to stop or substitute these medications …