Biopsy-proven tyrosine kinase inhibitor-associated renal injury: a case series

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.

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.

The cohort included 16 patients with solid tumors and 5 with hematologic malignancies exposed to four major TKI classes: vascular endothelial growth factor receptor, platelet-derived growth factor receptor, human epidermal growth factor receptor and Bruton's tyrosine kinase 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 1.83 g/day. Histopathological analysis demonstrated thrombotic microangiopathy (TMA)-like lesions in 17 of 21 cases (80%), with concurrent immunoglobulin A 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 angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker 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 five 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.

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.