Biopsy-Proven Tyrosine Kinase Inhibitor-Associated Renal Injury: A Case Series

Background and Hypothesis Tyrosine kinase inhibitors (TKIs) are essential anticancer agents associated with substantial nephrotoxic potential. Although TKI-induced renal injury is increasingly recognized, comprehensive histopathological characterization remains limited due to insufficient renal biopsy data. This study characterizes the clinicopathological spectrum and outcomes of biopsy-proven TKI nephrotoxicity. Methods This retrospective study analyzed 21 patients with biopsy-proven TKI-associated renal injury identified between 2015 and 2025. Demographic characteristics, renal function indices, oncological profiles, and histopathological features were analyzed. Results The cohort included 16 patients with solid tumors and 5 with hematologic malignancies exposed to four major TKI classes: vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), human epidermal growth factor receptor (HER), and Bruton’s tyrosine kinase (BTK)-TKIs. The median time from TKI initiation to symptom onset was 9.5 months. Clinical manifestations included proteinuria (95%), edema (52%), and new-onset/worsened hypertension (47%). At biopsy, median serum creatinine was 1.07 mg/dl (94.6 µmol/l) and proteinuria was 1.83g/d. Histopathological analysis demonstrated thrombotic microangiopathy (TMA)-like lesions in 17 of 21 cases (80%), with concurrent IgA nephropathy in 3 cases and focal segmental glomerulosclerosis in 3 cases. Among 18 patients with available follow-up data, 14 discontinued their initial TKI therapy, with 5 transitioning to alternative TKIs. Treatment strategies included ACEI/ARB monotherapy (n=13) and combination therapy with corticosteroids/immunosuppressants (n=5). During a median follow-up period of 9.5 months, complete and partial proteinuria remission occurred in 5 cases each. Four patients died due to cancer progression, while renal function remained stable in the remaining patients without progression to end-stage renal disease. Conclusion TKI-induced renal injury characteristically presents with edema, hypertension, and significant proteinuria, with renal-limited TMA as the predominant histopathological finding. Timely recognition and prompt discontinuation of the offending TKI, coupled with appropriate supportive nephroprotective management, generally yield favorable long-term renal outcomes with preservation of kidney function.