Nephrotoxicity remains a concern with the newer generation of tyrosine kinase inhibitors (TKI), 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, in Orlando, Florida.

Citing shortcomings of the FDA adverse reporting system, investigators performed a retrospective study of real-world data from 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.

The median duration of TKI therapy ranged from 28 to 67 days, Omar Mamlouk, MD, of of MD Anderson reported on behalf of his team. Proteinuria developed in 39% to 61% patients, depending on the TKI. Proteinuria was more frequent with regorafenib (61%) than axitinib (39%).

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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 irbutinib to 28% with ponatinib. The AKI rate with the newer TKIs is similar to the rate with the first-generation, Dr Mamlouk pointed out, with the exception of 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 risk of developing proteinuria and AKI, respectively, during TKI therapy.

“Around 50% of the patients develop any degree of proteinuria and 10-28% 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 with Renal & Urology News.

“Follow the recommendation of each TKI manufacturer for the frequency and timing of lab monitoring,” he added. “Generally, we suggest obtaining basic metabolic panel and urine protein to creatinine ratio prior to starting TKI then basic metabolic panel monthly after starting TKI in patients with stable kidney function.”


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.