Kidney function changes associated with trastuzumab use in women with breast cancer: a retrospective cohort study

Higher concentrations of human epidermal growth receptor 2 (HER2) may cause chronic kidney disease. We sought to determine if trastuzumab (a HER2 inhibitor) may be kidney protective.

Retrospective cohort study using administrative datasets. Women from Ontario, Canada with new stage 1-3 breast cancer between April 2009 and March 2019 were included. We matched trastuzumab users (n = 6,557) 1:1 with non-users on baseline eGFR, urine albumin-to-creatinine ratio (ACR), heart failure and propensity score. Change in eGFR was examined using linear mixed models. Secondary outcomes of ≥ 30 and ≥ 40% eGFR decline, incident eGFR < 60 mL/min/1.73 m² and heart failure were examined using Cox proportional hazards models. Follow-up was 3 years.

The linear mixed model showed no significant interaction between treatment with trastuzumab and time (estimate 0.11, 95% CI -0.01 to 0.23, ml/min/1.73 m²/year). There was an increased risk of ≥ 30% eGFR decline (HR 1.82, 95% CI 1.58 to 2.09), incident eGFR < 60 mL/min/1.73 m² (HR 2.09, 95% CI 1.52 to 2.88) and heart failure (HR 8.07, 95% CI 5.91 to 11.02) associated with trastuzumab use at ≤ 1.5 years but not > 1.5 years. There was an increased risk of ≥ 40% eGFR decline associated with trastuzumab use at 3 months (HR 3.06, 95% CI 1.85 to 5.08) but not beyond 3 months.

Trastuzumab was not associated with change in eGFR over 3 years but was associated with increased risk of ≥ 30% and ≥ 40% eGFR decline and new eGFR < 60 mL/min/1.73 m² at earlier time points, potentially mediated by the increased heart failure risk observed with trastuzumab.