Nephrotoxicity remains a concern with the newer generation of tyrosine kinase inhibitors (TKIs), with proteinuria and acute kidney injury (AKI) occurring in a subset of users, investigators reported at Kidney Week 2022, the annual meeting of the American Society of Nephrology.
Citing shortcomings of the US Food and Drug Administration’s adverse reporting system, investigators performed a retrospective study of real-world data from the University of Texas MD Anderson Cancer Center in Houston.
From January 2017 to October 2019, clinicians most commonly prescribed the TKIs regorafenib, axitinib, cabozantinib, erlotinib, ponatinib, and ibrutinib. Among 2063 patients (median age, 63 years), approximately half received ibrutinib.
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The median duration of TKI therapy ranged from 28 days to 67 days. Proteinuria developed in 39% to 61% patients, depending on the TKI. Proteinuria was more frequent with regorafenib (61%) than with axitinib (39%).
AKI developed in 1.5% of TKI users within 30 days and in 11.1% after 30 days. The proportion of patients experiencing AKI ranged from 10% with ibrutinib to 28% with ponatinib.
The AKI rate with the newer TKIs is similar to the rate with the first-generation, said study author Omar Mamlouk, MD, of MD Anderson. The exception is ponatinib, which carried a 2- to 3-fold higher risk of AKI.
In univariate analysis, diabetes and proton pump inhibitors were significantly associated with increased risks of developing proteinuria and AKI, respectively, during TKI therapy.
“Around 50% of the patients develop any degree of proteinuria, and 10% to 28% of the patients develop AKI while on TKI therapy. Despite the potential association with renal manifestations, the choice of TKI should still be made based on the superior cancer outcome rather than the risk of nephrotoxicity,” Dr Mamlouk said in an interview.
“Follow the recommendation of each TKI manufacturer for the frequency and timing of lab monitoring,” he added. “Generally, we suggest obtaining a basic metabolic panel and urine protein-to-creatinine ratio prior to starting TKIs, then a basic metabolic panel monthly after starting TKIs in patients with stable kidney function.”
Reference
Ratanasrimetha P, Mamlouk O, Achi SS, Long JP, Page VD, Mandayam SA. Real-world incidence of kidney manifestations in patients treated with new tyrosine kinase inhibitors. Presented at: Kidney Week 2022; November 3-6, Orlando, Florida. Abstract FR-PO215.
This article originally appeared on Renal and Urology News
