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

Purpose — 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.

Methods — 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.

Results — 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.

Conclusion — 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.