Among patients with cancer receiving renally cleared medications, therapeutic drug levels are higher and adverse events more frequent when their estimated glomerular filtration rate (eGFR) based on cystatin is more than 30% lower than their eGFR based on serum creatinine.
Patients with cancer take numerous medications that require dose adjustment by eGFR, such as antibiotics, muscle relaxants, antiepileptic drugs, blood thinners, and antiarrhythmic medications, explained Meghan E. Sise, MD, MS, of Massachusetts General Hospital in Boston, Massachusetts, and colleagues. The investigators decided to assess the potential for adverse events within 90 days of use of 4 such medications: intravenous vancomycin and trimethoprim-sulfamethoxazole, the muscle relaxant baclofen, and digoxin for congestive heart failure or atrial fibrillation. All patients had stage 3 or higher chronic kidney disease based on the CKD-EPI race-free combined serum creatinine and cystatin C equation (eGFRcr-cys).
Using patient registry data, the investigators identified 543 of 1869 adults with cancer (29%) who had a cystatin-based eGFR (eGFRcys) that was more than 30% lower than their serum creatinine-based eGFR (eGFRcr) using race-free CKD-EPI equations. This discordant group appeared to have increased risks for vancomycin levels above the therapeutic range, hyperkalemia from trimethoprim-sulfamethoxazole use, baclofen toxic effect, high digoxin levels, and death compared with the concordant group who had an eGFRcys within 30% of eGFRcr, the investigators reported in JAMA Network Open.
Vancomycin trough levels greater than 30 μg/mL affected a significantly greater proportion of the discordant than concordant eGFR group: 24% vs 9%, the investigators reported. The discordant group had significant 2.6-fold increased odds for vancomycin levels more than 30 μg/mL.
In nonsignificant results, trimethoprim-sulfamethoxazole-related hyperkalemia (serum potassium exceeding 5.5 mEq/L) occurred in 22% vs 12%, respectively. Baclofen toxic effect occurred in 26% vs 0%, respectively, and supratherapeutic digoxin levels (exceeding 2.0 ng/mL) occurred in 29% vs 0%, respectively.
The discordant group had a significant 2-fold higher risk for 30-day mortality compared with the concordant group after adjusting for age, race, sex, ethnicity, baseline comorbidities, and other potential confounders, the investigators reported.
Serum creatinine-based eGFR particularly overestimates GFR in patients with sarcopenia, which along with frailty affects many patients with cancer, Dr Sise’s team noted.
“Overall, the findings suggest that relying on [serum creatinine]-based eGFR alone for medication dosing may be inadequate in patients with cancer and highlight the need to consider using eGFRcr-cys when the eGFRcys was more than 30% lower than the eGFRcr.”
Hypoalbuminemia and anemia were more often present in patients with cancer who had an eGFRcys that was more than 30% lower than the eGFRcr, the investigators reported. They noted that cystatin C levels can be affected by acute inflammation, obesity, thyroid disease, and corticosteroid use.
Among the study’s limitations, the investigators did not have measured GFR values, which prevented them from determining the best method for assessing kidney function for medication dosing in the cancer population. In addition, eGFRcys measurements were not routinely obtained but ordered by the physician, which may introduce a selection bias. The investigators also lacked information on patients’ functional status and cancer stage.
“Future prospective studies are needed to improve and personalize the approach to GFR estimation and medication dosing in patients with cancer,” Dr Sise’s team concluded.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Hanna PE, Wang Q, Strohbehn IA, et al. Medication-related adverse events and discordancies in cystatin C-based vs serum creatinine-based estimated glomerular filtration rate in patients with cancer. JAMA Netw Open. Published online July 3, 2023. doi:10.1001/jamanetworkopen.2023.21715