Medication-related adverse events in patients with cancer and discrepancies in cystatin C- versus creatinine-based eGFR.

Background: Creatinine-based estimated glomerular filtration rate (eGFR) may overestimate kidney function in patients with cancer. Cystatin C-based eGFR (eGFR) is an alternative marker of kidney function. We investigated whether patients with an eGFR discrepancy, defined as eGFR >30% lower than the concurrent eGFR, had an increased risk of adverse events resulting from renally-cleared medications.

Patients And Methods: We conducted a cohort study of adult patients with cancer who had serum creatinine and cystatin C measured on the same day between May 2010 and January 2022 at two academic cancer centers in Boston, MA. The primary outcome was the incidence of each of the following medication-related adverse events: 1) supratherapeutic vancomycin levels (>30μg/mL); 2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5mEq/L); 3) baclofen-induced neurotoxicity; and 4) supratherapeutic digoxin levels (>2.0ng/mL).

Results: 1988 patients with cancer had simultaneous eGFR and eGFR. The mean age was 66 years (SD±14), 965 (49%) were female, and 1555 (78%) were non-Hispanic white. eGFR discrepancy occurred in 579 patients (29%). Patients with eGFR discrepancy were more likely to experience medication-related adverse events compared to those without eGFR discrepancy: vancomycin levels >30μg/mL (24% vs. 10%, p=0.004), trimethoprim- sulfamethoxazole-related hyperkalemia (24% vs. 12%, p=0.013), baclofen-induced neurotoxicity (25% vs. 0%, p=0.13), and supratherapeutic digoxin levels (38% vs. 0%, p=0.03). The adjusted OR for vancomycin levels >30μg/mL was 2.30 (95% CI 1.05 - 5.51, p = 0.047).

Conclusion: Among patients with cancer with simultaneous assessment of eGFR and eGFR, medication-related adverse events occur more commonly in those with eGFR discrepancy. These findings underscore the importance of accurate assessment of kidney function and appropriate dosing of renally-cleared medications in patients with cancer.