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Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum Creatinine-Based Estimated
Paul E Hanna1, Qiyu Wang1, Ian A Strohbehn1
1Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston.
Insights
In cancer patients, a significant difference between cystatin C-based (eGFRcys) and creatinine-based (eGFRcr) estimated glomerular filtration rate (GFR) indicates higher risks of supratherapeutic drug levels and adverse events. This highlights the need for personalized GFR assessment in oncology.
Area of Science:
- Nephrology
- Oncology
- Clinical Pharmacology
Background:
- Serum creatinine-based estimated glomerular filtration rate (eGFRcr) may overestimate actual kidney function in cancer patients.
- Cystatin C-based eGFR (eGFRcys) offers an alternative marker for assessing glomerular filtration rate (GFR).
Purpose of the Study:
- To investigate if higher therapeutic drug levels and adverse events (AEs) occur in cancer patients with a >30% lower eGFRcys compared to eGFRcr.
- To assess the association between eGFR discordance and medication-related AEs and mortality.
Main Methods:
- A cohort study of 1869 adult cancer patients from two academic centers.
- Simultaneous measurement of creatinine and cystatin C to calculate eGFRcr and eGFRcys.
- Primary exposure: eGFR discordance defined as eGFRcys >30% lower than eGFRcr.
- Primary outcomes: medication-related AEs (vancomycin, trimethoprim-sulfamethoxazole, baclofen, digoxin) within 90 days.
- Secondary outcome: 30-day mortality.
Main Results:
- 29% of patients (543/1869) had eGFR discordance.
- Patients with eGFR discordance had higher rates of supratherapeutic vancomycin levels (24% vs 9%), trimethoprim-sulfamethoxazole-related hyperkalemia (22% vs 12%), and trends towards more baclofen and digoxin toxicity.
- Adjusted odds ratio for supratherapeutic vancomycin was 2.59 (P=.04).
- eGFR discordance was associated with increased 30-day mortality (aHR, 1.98; P=.003).
Conclusions:
- eGFR discordance, specifically eGFRcys >30% lower than eGFRcr, is linked to increased supratherapeutic drug levels and medication-related AEs in cancer patients.
- This discordance also correlates with higher 30-day mortality.
- Further prospective studies are warranted to refine GFR estimation and personalize drug dosing in this population.
Importance:
Serum 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.
Objective:
To 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 Participants:
This 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.
Exposure:
The primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr.
Main Outcomes And Measures:
The 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.
Results:
A 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 Relevance:
Results 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.
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