Medicines

Checkpoint inhibitors may cause renal impairment with long term use


Immune checkpoint inhibitors (ICIs) may cause chronic renal toxicity in addition to their know acute adverse effects on the kidney, US research has found.

A retrospective cohort study that assessed kidney function in 2563 cancer patients receiving long term treatment with ICIs at the Mass General Brigham cancer centre found that new-onset chronic kidney disease (CKD) or a clinically significant decline in eGFR was common.

The study, which followed up patients who had survived more than one year after starting ICI treatment found that 13% developed signs of chronic kidney injury after a median of 471 days after the first ICI dose.

The primary outcome was a composite of new-onset CKD (eGFR <60 mL/min/1.73m for >90 days), 30% eGFR decline and kidney transplant.

More than one third of patients (35%) who survived more than three years showed signs of “rapid eGFR decline”, (defined as >3mL/min/1.73m per year).

There was also significant acceleration of eGFR decline after ICI initiation (1.4mL/min/year average decline prior to treatment, increasing to 3.7mL/min/year decline after initiation, p=0.012)

Older age and proton pump inhibitor use were independent predictors of renal decline with ICI, but not type of agent used.

The study investigators noted that ICIs had been available for more than a decade, but until now there had been little data about their long term toxicity on the kidney.

They said any effect that accelerated long decline in kidney function would be of concern given that ICIs were now coming into widespread use for cancer patients, who were often surviving for many years on treatment.

“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 enrolment,” they wrote.

However, because widespread use of ICI only began in 2015, the number of patients with more than four years follow-up is small and the findings will need to be validated in other cohorts with longer follow-up, they said.

“Future studies will be needed to determine the pathophysiology of kidney function decline after ICIs and evaluate strategies to slow eGFR decline,” they added.

The findings are published in the American Journal of Kidney Diseases.

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