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Patients with cancer are at risk for potentially deadly toxicities from chemotherapy overtreatment if kidney function is not accurately estimated beforehand. New research suggested that the use of creatinine and cystatin C measurements may provide a more accurate alternative to the widely used Cockcroft-Gault creatinine clearance.

“Based on these and other findings for chemotherapy when accurate assessment of kidney function for drug dosing matters, moving away from Cockcroft-Gault creatinine clearance to more accurate methods such as the estimated glomerular filtration rate (eGFR) with both creatinine and cystatin C [and/or other measures] should be considered,” Joseph A. Vassalotti, MD, chief medical officer of the National Kidney Foundation (NKF), told Medscape Medical News.

The findings were presented this week at the National Kidney Foundation (NKF) 2025 Spring Clinical Meetings.

As many as 32% of patients with cancer have chronic kidney disease at baseline, according to the NKF, and while cancer malignancy, as well as chemotherapy treatment, can pose the risk for acute kidney injury (AKI), standardized approaches to estimate GFR in the cancer population are lacking.

While measured GFR (mGFR) represents the gold standard of an exogenous filtration marker, it is considered burdensome due to factors including its complexity and cost, and it is not commonly used in clinical practice.

Cockcroft-Gault, a formula based on the patient’s serum creatinine, age, weight, and gender, remains the most used GFR estimation measure in cancer clinical trials and in many clinical settings, despite possibly having the potential to overestimate GFR, particularly among those with obesity or lower GFR levels.

Alternative endogenous markers include the Chronic Kidney Disease Epidemiology Collaboration equation 2021 creatinine and cystatin C equation, which is considered to be the most accurate method of assessment.

To evaluate the effectiveness of eGFR using creatinine and cystatin C (eGFR-Cr-Cys) compared with the Cockcroft-Gault equation in determining carboplatin chemotherapy dosing and the incidence of adverse events (AEs), Si Yuan Khor, MD, of the Division of Nephrology, Massachusetts General Hospital, Boston, and colleagues conducted a prospective study of 292 adult patients with cancer treated at the hospital between 2023 and 2025.

All patients had data available on creatinine and cystatin C measurements prior to their first carboplatin dose, and the authors compared the dose administered on the basis of the Cockcroft-Gault equation with the dose calculated using eGFR-Cr-Cys.

Patients had a mean age of 66 years, and 66% were women; 36% had lung cancer, 32% gynecologic cancer, 12% intestinal cancer, and 11% had breast cancer.

The results showed that the application of eGFR-Cr-Cys would have led to clinically significant dose adjustments among 76 patients (26%).

In all, 35 patients (12%) received an excessive dose of carboplatin, defined as more than 15% higher than the dose calculated using eGFR-Cr-Cys, and 41 patients (14%) were underdosed by more than 15% than the eGFR-Cr-Cys–based dose.

The remaining 74% of patients received a dose within 15% of the dose predicted by eGFR-Cr-Cys.

Notably, an excessive carboplatin dose was significantly associated with more severe AEs, including an increased risk for anemia (grade 2 or higher, adjusted hazard ratio [aHR], 2.08; grade 3 or higher, aHR, 3.05), thrombocytopenia (grade 2 or higher, aHR, 2.83; grade 3 or higher, aHR, 3.46), AKI (grade 2 or higher increased creatinine, aHR, 1.19; grade 3 or higher, aHR, 6.50), and mortality (aHR, 3.16).

“Patients who were overtreated had a staggering 6.5 times greater likelihood of developing AKI and were at about a 3 times higher risk for death at 90 days,” Khor said.

In interpreting GFR estimations, Khor underscored consideration of risk factors that may skew cystatin D, including obesity, acute inflammatory state, corticosteroid use, and a high tumor burden.

“These are pretty common characteristics that you normally see in cancer patients, so it’s important that when you interpret cystatin C in cancer patients to remember that these might all falsely elevate cystatin C.”

Furthermore, discordances between creatinine and cystatin C are common and are important, as they are associated with poor outcomes in older adults and medication side effects.

In a separate poster presented at the meeting, Khor and his colleagues reported on the association of the ratio between serum creatinine and cystatin C and the risk for AEs with either carboplatin or cisplatin in the same patient population.

In the cohort of 441 patients beginning cisplatin or carboplatin for cancer, they found that having a creatinine/cystatin C ratio of less than 0.7 was associated with AEs and hospitalization, including anemia (grade ≥ 2 and ≥ 3, subdistribution hazard ratio [sHR], 1.56 and 2.71, respectively) and thrombocytopenia (grade 2, sHR, 1.78; grade 3 or higher, sHR, 4.54), AKI (grade ≥ 3, sHR, 7.27), as well as all-cause hospitalizations (sHR, 1.72) and hospitalizations for AEs within 90 days (sHR, 1.88).

Of note, patients with a ratio of < 0.7 also had an independent, 6.61-fold increased risk for death within 90 days (P < .001).

“This suggests that a discrepancy in cystatin C and creatinine is actually a strong predictor of death,” Khor said.

Onconephrology Society Recommendations

In guidance on the assessment of GFR in patients with cancer, the American Society of Onconephrology cautions that “clinicians should be aware of shortcomings of creatinine-based equations, and if possible, use validated GFR estimating equations incorporating serum creatinine and serum cystatin C for decision-making related to anticancer therapy eligibility and dose adjustment.”

They further recommend the avoidance of “non-validated equations, including the Cockcroft-Gault formula, for decision-making related to anticancer therapy eligibility and dose adjustment.”

When patients with cancer show borderline eligibility for specific therapies based on eGFR results, the society recommends obtaining an mGFR via exogenous filtration marker.

Further commenting on the research, Vassalotti, a clinical professor of nephrology at the Icahn School of Medicine at Mount Sinai, New York City, noted that many clinicians may be unaware of the level of risk presented by the potential overtreatment that can result from shortcomings in kidney function estimation.

“I think awareness is probably very low among practicing clinicians in general, but hopefully oncologist and nephrologists will increase awareness of the need for more precise and accurate assessment of kidney function for chemotherapy use,” he said.

“The evolving onconephrology subdiscipline should lead the way forward for investigation and education of nephrologists and oncologists for safer and optimally efficacious chemotherapy drug dosing,” he added.

The authors and Vassalotti had no disclosures to report.