Thread by @ShrutiGkidney

Do cyclin-dependent kinase (CDK) 4/6 inhibitors cause acute kidney injury (AKI)? #onconephrology #Thread

A little #tweetorial about CDK 4/6 inhibitor-associated AKI: what we know already, and what we found
kireports.org/article/S2468-…

3 CDK 4/6 inhibitors (palbociclib, ribociclib, and abemaciclib)have been approved for HER2-negative metastatic breast cancers. CDK 4/6 inhibitors help overcome resistance to endocrine therapies by preventing cell-cycle progression and cancer growth (frontiersin.org/articles/10.33…).

What do we know about AKI related to CDK 4/6 inhibition? In vitro studies suggest that CDK 4/6 inhibitor metabolites inhibit renal transporters, potentially leading to a reversible rise in serum creatinine (SCr) without actually changing GFR (ncbi.nlm.nih.gov/pmc/articles/P…).

Our objective: to present the first series of patients with biopsy-proven AKI associated with CDK4/6 inhibitors, with a focus on clinical features and pathologic findings, and to query the FAERS database for renal adverse events related to CDK 4/6 inhibitors

Histopathology: 6 patients treated at 3 different centers had biopsy-proven AKI that was directly attributable to the CDK 4/6 inhibitor by the treating nephrologist. Acute tubular injury was the most common pathology, though one patient had acute tubulointerstitial nephritis

Repercussions of AKI: AKI required dose reduction and or discontinuation of therapy in 4 of 6 patients

Reporting of renal related adverse events: The most common renal adverse event was renal injury, but electrolyte abnormalities were reported as well, including hypokalemia, hyponatremia, and hypocalcemia

Though CDK4/6 inhibitors may lead to a reversible rise in SCr, they can also cause true renal tubular toxicity and metabolic disturbances. We now need larger, prospective studies to understand and characterize the incidence of and risk factors for AKI

This collaborative effort would not have been possible without @kdjhaveri, @Tiff_Caza, @herrmannMd, and Vipul Sakhiya. @bwhkidney, #HofNorthwellDOM, @NorthwellHealth, @arkanalabs, @MayoClinicNeph, @KIReports

And thank you to @edgarvlermamd for this stunning visual abstract @threadreaderapp #unroll