Immune checkpoint inhibitors linked to rapid eGFR decline, development of kidney disease
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For patients with cancer, the use of immune checkpoint inhibitors was associated with rapid eGFR decline and the subsequent development of chronic kidney disease 1 year after therapy initiation, study findings showed.
“Initially approved in 2010 for patients with metastatic melanoma, immune checkpoint inhibitors (ICIs) are now approved for more than 17 different cancer types, and it is estimated that one in three patients with cancer now qualify for ICIs,” Donald F. Chute, BS, of the division of nephrology at Massachusetts General Hospital, and colleagues wrote. “ICIs remove key regulators of T-cell function to unleash anti-tumor effects, but T-cell disinhibition can also lead to immune-related adverse events, affecting as many as 60[% to] 85% of patients. Though the epidemiology of ICI-induced acute kidney injury has been well characterized, there is extremely limited data on the long-term toxicities of ICIs.”
With that in mind, Chute and colleagues examined the impact of ICIs on kidney function in 2,563 adults who survived for at least 1 year following treatment initiation (32% had melanoma; 28% had lung cancer). Patients were followed for a median of 688 days, with researchers considering a composite outcome of new onset CKD, a 30% decline in eGFR or the need to start renal replacement therapy.
In total, 13% of the study population developed the composite outcome, which occurred at a median of 471 days after the first ICI dose (the incident rate was 6.34 per 100-patient years).
Results showed new onset CKD or a clinically significant decline in eGFR was common in patients treated with ICIs. More specifically, an eGFR decline of greater than 3 mL/min/1.73 m2 (termed “rapid” kidney function decline) affected 35% of patients who survived for at least 3 years, with researchers observing a significant acceleration of eGFR decline after ICI initiation (a decline of 1.4 mL/min/1.73 m2 per year prior to ICI initiation compared with a decline of 3.7 mL/min/1.73 m2 per year after ICI initiation).
“Our study has important implications for patients treated with ICIs; a subset of survivors may experience significant eGFR decline that may contribute to long-term health consequences and may limit the use or dosage of other anticancer drugs and eligibility for clinical trial enrollment,” Chute and colleagues concluded. “We identified age and use of proton pump inhibitors as important risk factors for new onset CKD and sustained 30% eGFR decline; both have previously been shown to be risk factors for AKI patients with cancer. Future studies will be needed to determine the pathophysiology of kidney function decline after ICIs and evaluate strategies to slow eGFR decline.”
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