Medication-Related Adverse Events and Discordancies in Cystatin C–Based vs Serum Creatinine–Based Estimated Glomerular Filtration Rate in Patients With Cancer

Abstract

ImportanceSerum creatinine–based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C–based eGFR (eGFRcys) is an alternative marker of GFR.ObjectiveTo determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr.Design, Setting, and ParticipantsThis cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date.ExposureThe primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr.Main Outcomes and MeasuresThe primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 μg/mL, (2) trimethoprim-sulfamethoxazole–related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance.ResultsA total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 μg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole–related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 μg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003).Conclusions and relevanceResults of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.

Sarcopenia, adiposity and large discordance between cystatin C and creatinine‐based estimated glomerular filtration rate in patients with cancer

“…Patients with cancer are commonly exposed to antineoplastic therapies or supportive medications (antibiotics, anticonvulsants and anticoagulants) that require dose adjustments based on kidney function; therefore, a large discordance between eGFR CRE and eGFR CYS poses significant challenges in clinical management and may be associated with adverse medication events and lower survival. 25 Sarcopenia is associated with decreased survival in patients with cancer and has been associated with increased treatment-related toxicity in patients receiving antineoplastic therapies. [26][27][28][29] We hypothesize that medication overdose due to inaccurate estimation of GFR when relying on eGFR CRE in patients with sarcopenia may cause dose-related toxicity in renally excreted chemotherapies 26 and may thereby contribute to the decreased survival in these patients.…”

“…Accurate assessment of eGFR is important but challenging in patients with cancer due to the high prevalence of sarcopenia and sarcopenic obesity. Patients with cancer are commonly exposed to antineoplastic therapies or supportive medications (antibiotics, anticonvulsants and anticoagulants) that require dose adjustments based on kidney function; therefore, a large discordance between eGFR CRE and eGFR CYS poses significant challenges in clinical management and may be associated with adverse medication events and lower survival 25 …”