Boston—Using immune checkpoint inhibitors as a treatment for cancer can put patients’ kidney health at risk, according to a new study.

In fact, an article in the Clinical Journal of the American Society of Nephrology points out that 17% experienced acute kidney injury (AKI), 8% experienced sustained AKI, and 3% had potential immune checkpoint inhibitor-related AKI.

Furthermore, Massachusetts General Hospital researchers and colleagues emphasize that use of proton-pump inhibitors, which are commonly prescribed for stomach ulcers or acid reflux, were associated with a higher risk of experiencing sustained AKI.

The authors point out that Immune checkpoint inhibitor use in oncology is increasing rapidly, leading them to try to determine the frequency, severity, cause, and predictors of AKI in a real-world population receiving checkpoint inhibitors.

Included in the study were all patients who received checkpoint-inhibitor therapy from May 2011 to December 2016 at Massachusetts General Hospital. Researchers compared baseline serum creatinine, averaged 6 months before checkpoint inhibitor start date, with all subsequent creatinine values within 12 months of starting therapy. Overall, 1,016 patients, average age 63 years, were included in the analysis. Most, 61%, of participants were men, and 91% were white. Mean baseline creatinine was 0.9 mg/dl (SD 0.4 mg/dl), and 169 (17%) had CKD (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m2) at baseline.

To define AKI, the study used Kidney Disease: Improving Global Outcomes criteria. The primary outcome was sustained AKI events, defined as those lasting at least 3 days, and researchers determined the cause of sustained AKI by chart review.

Results indicate that 169 patients (17%) experienced AKI, defined by an increase in creatinine at least 1.5 times the baseline within 12 months; 82 patients (8%) experienced sustained AKI; and 30 patients (3%) had potential checkpoint inhibitor–related AKI.

The study determined that the first episode of sustained AKI occurred an average of 106 days (SD 85) after checkpoint-inhibitor initiation. In addition, 16 (2%) patients experienced stage 3 sustained AKI and four patients required dialysis. Proton-pump inhibitor use at baseline was associated with sustained AKI, the report noted.

“AKI is common in patients receiving checkpoint inhibitor therapy,” the authors conclude. “The causes of sustained AKI in this population are heterogenous and merit thorough evaluation. The role of PPI and other nephritis-inducing drugs in the development of sustained AKI needs to be better defined.”

Background information in the articles explains that immune checkpoint inhibitors act by releasing the natural breaks on immune activation and enhancing the immune system’s ability to destroy tumor cells. Approved agents target checkpoint pathways mediated by cytotoxic T lymphocyte–associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1), and programmed death ligand 1 (PDL1).

“Checkpoint inhibitors have produced durable responses in a subset of patients with cancer, but the benefit comes at a cost. Unchecked activation of the immune system may cause multisystem, immune-related adverse events, which can be fatal,” the authors write. “Acute interstitial nephritis (AIN) is the most common biopsy-proven diagnosis in patients on checkpoint inhibitors who develop AKI.”

The study notes that American Society of Clinical Oncology guidelines currently recommend interrupting checkpoint-inhibitor therapy and evaluating any patient whose serum creatinine rises 1.5-fold above baseline i.e., ≥ stage 1 AKI. The guidelines recommend an empirical course of steroids for a patient with stage 2 AKI when an alternate cause cannot be identified.

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