What is it about?
Doctors usually judge kidney function from creatinine, a waste product measured in a routine blood test. Abemaciclib, a drug for breast cancer, raises blood creatinine. It does so by blocking the transport proteins that carry creatinine from the blood into the urine, not because the kidneys are failing. We studied 63 Japanese patients with breast cancer receiving abemaciclib, 62 women and one man, and measured cystatin C in all of them. Cystatin C is a second blood marker of kidney function that these transport proteins do not carry. Creatinine rose in 62 of the 63 patients. Cystatin C did not rise, and in the patients who also had a sample from before treatment it fell slightly. If kidney function had truly declined, both markers would have risen together. In half of the patients with a before-treatment sample, 15 of 29, the two markers already disagreed before the drug was started. In an exploratory analysis, a common genetic variant in one of the transport proteins was associated with how much creatinine rose. That finding needs confirmation in other groups of patients.
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Why is it important?
A rise in creatinine often triggers dose reductions, treatment breaks, and extra kidney investigations. When the rise does not reflect a loss of kidney function, those steps carry a cost without a benefit, and they can interrupt effective cancer treatment. Earlier studies measured cystatin C in only a minority of patients, or not at all, so how often the two markers disagree was unclear. We measured it in every patient and found the disagreement in 62 of the 63. The same data show why one measurement during treatment is not enough. In half of the patients we could check, the gap was already there before the drug was started, so a single value cannot separate a drug-related gap from a pre-existing one. What carries the information is the change within each patient, which means cystatin C is worth measuring before treatment starts rather than after creatinine rises. The rise itself was mild. It was grade 1 on the standard toxicity scale in 57 of the 63 patients, none reached grade 3 or higher, it stayed stable through 24 weeks, and it fell in 14 of the 15 treatment interruptions we could evaluate. No patient in this study had a dose changed for kidney reasons.
Perspectives
The problem behind this study is an ordinary one. A number on a routine blood test changes, and a clinician has to decide that day whether to hold a cancer drug. We started by asking how often the two markers disagree, and the answer turned out to depend on a value most hospitals never record: what the patient's cystatin C was before treatment began. I hope this encourages teams to take that measurement at the start, when it is simple to do, rather than trying to reconstruct it afterwards.
Keita Hirai
Wakayama Medical University
Read the Original
This page is a summary of: Creatinine–Cystatin C Discrepancy and Renal Transporter Polymorphisms in Japanese Patients with Breast Cancer Receiving Abemaciclib, Clinical Pharmacology & Therapeutics, September 2026, Wiley,
DOI: 10.1002/cpt.70490.
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