Osimertinib-induced Pseudo-AKI: A case of creatinine elevation with preserved glomerular function

Introduction: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have been used in treating non-small cell lung cancer (NSCLC). Osimertinib is a third generation TKI targeting NSCLC with EGFR mutation. It is well know TKIs can cause pseudo-acute kidney injury (AKI) due to the inhibition of tubular secretion of creatinine. The effect of Osimertinb on kidney function has not been well established. Here we reported a case of osimertinub associated elevation of creatinine, yet normal Cystatin-C. Case description: A thirty-nine-year-old male non-smoker with stage IVB lung adenocarcinoma was started on osimertinib in spring 2024. His baseline creatinine was 1–1.2 mg/dL, increased to 1.7 mg/dL 1 month after the initiation of osimertinib, then remained at 1.6–1.7 mg/dL. Due to no obvious reason for his elevation of creatinine, serum Cystatin-C level was checked, which was within normal range. Repeat serum creatinine shown persistent elevation and repeat Cystatin-C were all within normal range. We hypothesized that the elevation of creatinine was due to osimertinib inhibits proximal tubular secretion of creatinine. Discussion: Serum creatinine level is affected by both glomerular filtration and tubular secrtion. Many medications inhibits tubular secretion of creatinine, for example: trimethoprim, cimetidine, pyrimethamine, and others. On the other hand, Cystatin-C is not secreted by proximal tubule, so the serum level closely reflect glomerular filtration rate. Clinicians need to be aware of this effect of osimertinib, thus avoid stopping an effective life saving medication for patients with NSCLC.