Discordance among creatine and cystatin based eGFR may predict drug related adverse events in cancer patients

Patients with cancer often undergo renal function assessment using serum creatinine-based estimated glomerular filtration rate (eGFRcr). However, this method may overestimate the actual glomerular filtration rate (GFR) in this population. An alternative marker of GFR is cystatin C-based estimated GFR (eGFRcys). A recent cohort study published in JAMA Network Open by Paul E. Hanna and a team of researchers conducted at two major academic cancer centers aimed to investigate whether patients with cancer who had a significant difference between eGFRcys and eGFRcr experienced higher levels of therapeutic drugs and adverse events (AEs) associated with renally cleared medications.

The study included 1,869 adult patients with cancer who had simultaneous measurements of eGFRcys and eGFRcr. Among them, 543 patients (29%) had an eGFRcys that was more than 30% lower than their eGFRcr, indicating discordance between the two measures. The primary outcome assessed the risk of medication-related AEs within 90 days of the baseline date, including supratherapeutic vancomycin levels, trimethoprim-sulfamethoxazole-related hyperkalemia, baclofen toxic effects, and supratherapeutic digoxin levels. The secondary outcome examined the 30-day survival rate in patients with and without eGFR discordance.

● The findings showed that patients with an eGFRcys more than 30% lower than their eGFRcr had a higher likelihood of experiencing medication-related AEs compared to patients with concordant eGFRs.

● Specifically, they had a higher incidence of supratherapeutic vancomycin levels (24% vs. 9%), trimethoprim-sulfamethoxazole-related hyperkalemia (22% vs. 12%), baclofen toxic effects (26% vs. 0%), and supratherapeutic digoxin levels (29% vs. 0%).

● After adjusting for potential confounding factors, the odds of having vancomycin levels greater than 30 μg/mL were 2.59 times higher in patients with discordant eGFRs.

● Furthermore, patients with eGFRcys more than 30% lower than their eGFRcr had increased 30-day mortality compared to those with concordant eGFRs.

These results suggest that patients with cancer who show a significant difference between eGFRcys and eGFRcr are at a higher risk of experiencing supratherapeutic drug levels and medication-related AEs. Moreover, their 30-day mortality rate has increased. The study highlights the need for future prospective studies to develop improved methods for estimating GFR and tailoring medication dosing specifically for patients with cancer. Personalized approaches to renal function assessment and drug dosing could enhance patient safety and optimize treatment outcomes in this population.

Reference:

Hanna, P. E., Wang, Q., Strohbehn, I. A., Moreno, D., Harden, D., Ouyang, T., Katz-Agranov, N., Seethapathy, H., Reynolds, K. L., Gupta, S., Leaf, D. E., & Sise, M. E. (2023). Medication-related adverse events and discordancies in cystatin C–based vs serum creatinine–based estimated glomerular filtration rate in patients with cancer. JAMA Network Open, 6(7), e2321715. https://doi.org/10.1001/jamanetworkopen.2023.21715