Volumetric absorptive microsampling as alternative sampling technique for renal function assessment in the paediatric...

Area of Science:

• Nephrology
• Clinical Chemistry
• Analytical Chemistry

Background:

• Glomerular filtration rate (GFR) is the primary indicator of overall kidney function.
• Iohexol is a promising exogenous marker for assessing GFR.
• Conventional blood sampling for iohexol quantification can be invasive, especially in pediatric patients.

Purpose of the Study:

• To evaluate the suitability of volumetric absorptive microsampling (VAMS) as an alternative to conventional blood sampling for iohexol quantification in pediatric plasma.
• To develop and validate a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for iohexol measurement using VAMS.
• To assess the clinical applicability of VAMS by comparing iohexol concentrations and derived GFR values with those obtained from traditional plasma sampling.

Main Methods:

• Development and validation of a novel LC-MS/MS method for iohexol quantification.
• Application of the VAMS technique for collecting pediatric plasma samples.
• Comparative analysis of VAMS-derived iohexol levels and GFR with conventional plasma-based measurements in 20 pediatric patients.

Main Results:

• The developed LC-MS/MS method was simple, cost-effective, and met all validation criteria.
• Accurate iohexol quantification was achieved within a hematocrit range of 20-60%.
• Long-term stability of iohexol in VAMS was confirmed for up to 245 days under various storage conditions.
• Excellent correlation was observed between VAMS and conventional plasma methods for both iohexol concentrations (r=0.98) and GFR values (r=0.99).
• Good agreement was found for GFR > 60 mL/min/1.73 m², with acceptable bias for both methods.
• Slightly lower accuracy was noted for GFR < 60 mL/min/1.73 m², suggesting potential for protocol optimization.

Conclusions:

• VAMS is a suitable and reliable alternative to conventional blood sampling for pediatric GFR assessment using iohexol.
• The validated LC-MS/MS method provides accurate and stable quantification of iohexol from microsamples.
• While effective for higher GFRs, minor adjustments to the VAMS protocol may enhance accuracy for lower GFR values in pediatric patients.