image: Figure: Elevated creatinine levels do not necessarily indicate impaired kidney function: pre-treatment cystatin C measurement is key to assessment
In 63 patients with breast cancer receiving abemaciclib, serum creatinine and cystatin C were measured before and during treatment, and polymorphisms of renal transporters involved in creatinine secretion were analyzed. Serum creatinine rose in 62 of the 63 patients, whereas cystatin C fell in 28 of the 29 patients who had a pre-treatment measurement. Patients with the SLC47A1 rs2289669 GG genotype, in which MATE1 function is preserved, tended to show a larger creatinine rise. Measuring cystatin C before treatment helps avoid unnecessary dose reductions, treatment interruptions, and additional tests.
Credit: Data panels adapted from Watanabe H, et al. Clin Pharmacol Ther (2026). All icons were obtained from bioicons.com and modified.
A routine blood test can make a kidney look like it is failing when it is not. A team from Kanazawa University and Shinshu University has shown that this happens often in patients with breast cancer who take abemaciclib, and that a simple baseline measurement can help doctors tell the difference.
Abemaciclib is widely used for hormone receptor–positive breast cancer. It is known to raise serum creatinine, the standard marker used to estimate kidney function. Because creatinine is also pushed out of the body by transporter proteins in the kidney, the rise may reflect blocked transport rather than damaged kidneys. In practice, however, a higher creatinine can still lead to dose reductions, treatment interruptions, or extra tests.
The researchers followed 63 patients (62 women and 1 man) at Shinshu University Hospital. Creatinine rose in 62 of the 63 patients, from a median of 0.63 to 0.85 mg/dL, and the rise stayed stable through 24 weeks of treatment. It fell back after treatment was interrupted. In the 29 patients whose blood had been tested for cystatin C both before and during treatment, cystatin C showed a different pattern. In 28 of them, creatinine and cystatin C moved in opposite directions. Cystatin C is a protein that is not secreted by the same transporters, so it is less affected by the drug.
Another finding was that, in 15 of the 29 patients (52%), the two markers already disagreed before treatment began. Without a baseline cystatin C, such a gap can be mistaken for a drug effect or for kidney damage.
The team also looked at a gene for the transporter MATE1 (SLC47A1). Patients with the GG type of the rs2289669 variant, which is thought to keep the transporter fully active, tended to show a larger creatinine rise. This result is exploratory and needs confirmation in larger studies.
Researcher Quote
“When creatinine rises after starting abemaciclib, it does not necessarily mean the kidneys are failing. What surprised us was that, in about half of the patients we could examine, creatinine and cystatin C already disagreed before treatment began. We therefore recommend measuring cystatin C at baseline, so that each patient has a personal reference point and can stay on an effective therapy without unnecessary dose reductions or interruptions.” — Hiroaki Watanabe, Assistant Professor, Faculty of Pharmacy, Kanazawa University
Funders
This work was supported by JSPS KAKENHI Grant Number JP24K18307.
Journal
Clinical Pharmacology & Therapeutics
Article Title
Creatinine–Cystatin C Discrepancy and Renal Transporter Polymorphisms in Japanese Patients with Breast Cancer Receiving Abemaciclib
Article Publication Date
22-Sep-2026