Creatinine-Cystatin C Discrepancy and Renal Transporter Polymorphisms in Japanese Patients with Breast Cancer...

Abemaciclib increases serum creatinine by inhibiting renal tubular transporters rather than reducing true glomerular filtration rate, a phenomenon known as pseudo-acute kidney injury. Creatinine-cystatin C discrepancy and genetic determinants of this elevation remain insufficiently characterized in Japanese patients. This single-center prospective observational study included 63 Japanese patients with breast cancer receiving abemaciclib. On-treatment serum creatinine and cystatin C were measured in all patients, with pre-treatment cystatin C available in 29. eGFR was calculated using the Japanese equations (eGFRcre, eGFRcys), and the discrepancy quantified as their difference and ratio. Associations between change in serum creatinine and renal transporter polymorphisms (SLC22A2 rs316019, SLC47A1 rs2289669, and SLC47A2 rs12943590) were evaluated by hierarchical regression. Serum creatinine increased in 62 patients (median change, 0.21 mg/dL) and eGFRcre decreased by a median of 20.5 mL/min/1.73 m², whereas on-treatment eGFRcys exceeded eGFRcre by a median of 54.9 mL/min/1.73 m² (median ratio 2.07). Relative to baseline, the elevation was CTCAE grade 1 in 57 patients (90.5%) and grade 2 in 5 (7.9%), remained stable through week 24, and fell after drug interruption (0.87 to 0.71 mg/dL, P < 0.001). In the 29-patient sub-cohort the discrepancy widened approximately three-fold, with opposite directional changes in 28 patients. The pre-treatment serum creatinine/cystatin C ratio predicted the on-treatment discrepancy, and SLC47A1 rs2289669 GG was associated with a greater rise, consistent with a MATE1-mediated mechanism. Because a fixed cross-sectional threshold does not separate treatment-associated discrepancy from pre-existing discrepancy, a pre-treatment cystatin C measurement is needed to interpret serum creatinine elevation during abemaciclib therapy.