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PD-1 inhibitors may increase risk for AKI, hypocalcemia
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The risk for developing AKI and hypocalcemia may be higher for patients treated with PD-1 inhibitors than those treated with non-nephrotoxic agents, according to a recently published study.
“Our study shows the risk of developing acute kidney injury in patients treated with PD-1 inhibitors is not high (2% of patients) but four-times higher than seen with other non-nephrotoxic chemotherapy drugs,” Sandra M. Herrmann, MD, assistant professor of medicine and consultant in the division of nephrology and hypertension at Mayo Clinic in Rochester, Minnesota, told Healio/Nephrology. “PD-1 inhibitors can cause AKI and electrolyte abnormalities, which can be severe and need to be recognized and treated to avoid debilitating and even life-threatening complications.”
After conducting a systemic search of published literature on clinical trials that monitored electrolyte levels and kidney function during treatment with nivolumab or pembrolizumab, researchers conducted a meta-analysis of 48 trials (11,482 patients).
Researchers found the overall pooled risk ratio of all AKI in patients treated with PD-1 inhibitors was 1.86 (95% CI, 0.95-3.64) and that the overall pooled risk ratio of all electrolyte abnormalities in these patients was 1.67 (95% CI, 0.89-3.12).
When researchers compared PD-1 inhibitors with the non-nephrotoxic controls, they found the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI, 1.57-11.18), with the incidence rate of AKI being 2.2% (95% CI; 1.5-3%). In addition, prespecified subgroup analyses revealed an association between PD-1 inhibitors and hypocalcemia (pooled RR = 10.87; 95% CI, 1.40-84.16). Researchers also found the pooled estimated rate of interstitial nephritis was 16.6% (95% CI, 10.2-26%) in patients who developed AKI with PD-1 inhibitors.
“Additional studies are needed to evaluate potential risk factors for the development of [immune-checkpoint inhibitor]ICI-related AKI and electrolyte abnormalities,” Herrmann said. “Furthermore, best practices for monitoring and managing such complications need to be established. A key question is if and how to continue ICI therapy in view of evolving complications. Once resolved, can patients be re-challenged? What is the long-term implication of such renal injuries, besides the molecular mechanisms? There is still much to learn.” – by Melissa J. Webb
Disclosures: The authors report no relevant financial disclosures.
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