Correlation Between Renal Biomarkers, Glomerular Filtration Rate, and Meropenem Clearance in Pediatric Septic Shock

Area of Science:

• Pediatric Nephrology
• Clinical Pharmacology
• Critical Care Medicine

Background:

• Accurate estimation of renal function is crucial for appropriate drug dosing in pediatric patients, especially those with critical illnesses like sepsis.
• Meropenem clearance (CL MERO) can be significantly affected by variations in renal function, including acute kidney injury (AKI) and augmented renal clearance (ARC).
• Existing estimated glomerular filtration rate (eGFR) methods are widely used but their reliability in critically ill children with fluctuating renal function is not well-established.

Purpose of the Study:

• To evaluate the correlation between various eGFR estimation methods and observed meropenem clearance (CL MERO) in hospitalized children.
• To identify the accuracy of different eGFR equations in detecting AKI and ARC in this population.
• To understand the variability of renal function in critically ill children, particularly those with sepsis.

Main Methods:

• A prospective study involving 27 children (aged 4 weeks to 21 years) receiving meropenem (20mg/kg IV every 8 hours) between 2019 and 2023.
• Comparison of sepsis cases (n=19) with controls (n=8), measuring plasma meropenem concentrations and renal function biomarkers (serum creatinine [SCr], cystatin C [SCys]).
• GFR was estimated using multiple methods: eGFR-MS (modified Schwartz/CKD-EPI), eGFR-Cr, eGFR-Cys, eGFR-Avg (Pierce equations), and eGFR-Pot (Pottel).

Main Results:

• Analysis of 309 meropenem serum concentrations revealed a weak correlation (Spearman Rho 0.073–0.14) between all tested eGFR methods and CL MERO.
• Significant discordance (41%) was observed between SCr-based and SCys-based eGFR in identifying ARC and AKI.
• Renal function in critically ill children, especially those with sepsis, demonstrated extreme daily diversity and variability.

Conclusions:

• Current eGFR estimation methods exhibit poor correlation with actual meropenem clearance in hospitalized children.
• The high variability and unpredictability of renal function in critically ill children, particularly with sepsis, pose challenges for accurate therapeutic drug monitoring.
• Further research is needed to develop more reliable methods for assessing renal function in this vulnerable pediatric population to optimize antibiotic therapy.