Volumetric absorptive microsampling as alternative sampling technique for renal function assessment in the paediatric population using iohexol

Abstract

The glomerular filtration rate (GFR) is considered the best overall index for the renal function. Currently, one of the most promising exogenous markers for GFR assessment is iohexol. In this study, the suitability of volumetric absorptive microsampling (VAMS) as alternative for the conventional blood sampling and quantification of iohexol in paediatric plasma was assessed. Therefore, a new, fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed. Subsequently, the clinical suitability was evaluated in 20 paediatric patients by comparing plasma iohexol concentrations and associated GFR values obtained by the VAMS method with those obtained by conventional blood sampling and quantification of iohexol in plasma. The developed, simple and cost-effective LC-MS/MS-method fulfilled all pre-set validation acceptance criteria. Iohexol could be accurately quantified within a haematocrit range of 20-60% and long-term stability of iohexol in VAMS was demonstrated up to 245 days under different storage temperatures. Both iohexol plasma concentrations (r = 0.98, mean bias: − 4.20%) and derived GFR values (r = 0.99; mean bias: 1.31%), obtained by a conventional plasma and the VAMS method, demonstrated good correlation and acceptable bias. The agreement between the two methods was especially good for GFR values higher than 60 mL/min/1.73 m 2 . Nevertheless, for GFR values <60 mL/min/1.73 m 2 the accuracy compared to the plasma method was lower. However, small adjustments to the sampling protocol could probably solve this problem.

Volumetric microsampling for simultaneous remote immunosuppressant and kidney function monitoring in outpatient kidney transplant recipients

“…Third, no separate stability studies were performed for the VAMS samples during the analytical validation. However, previous studies have shown that tacrolimus, MPA and everolimus are stable in VAMS samples for 50 days in the freezer (À20 C), 60 days at room temperature, 30 days at 37 C and 2 days at 50 C. 43 Additionally, iohexol is stable in VAMS samples up to 8 months in the freezer (À20 C) or refrigerator (2-8 C) and 3 months at room temperature, 58 and creatinine for at least 14 days at 20 C, 7 days at 37 C and 25 days in the freezer (À20 C) or refrigerator (4 C). 38 As all VAMS samples for the clinical validation were analysed within 1 month after sample collection and stored at À20 C before analysis, no pronounced interference of analyte stability with our results was anticipated.…”

“…Similarly, others showed that tacrolimus, MPA, everolimus, creatinine and iohexol can be quantified reliably in VAMS samples with haematocrit values between approximately 0.20 and 0.60. 43,48,58 As haematocrit values outside these ranges are seldomly encountered in adult kidney transplant recipients, 93…”

“…Nevertheless, iohexol plasma clearancebased mGFR assessment has gained interest for clinical and research purposes, 50,51,53 and also harnesses options for (partially) remote determination utilising microsampling. [54][55][56][57][58] What is already known about this subject…”

“…Unfortunately, the available mGFR methods rely on extensive sampling, 50,53 which has hampered their application in routine care. Nevertheless, iohexol plasma clearance‐based mGFR assessment has gained interest for clinical and research purposes, 50,51,53 and also harnesses options for (partially) remote determination utilising microsampling 54–58 …”

Measurement of glomerular filtration rate and its current status in African countries GFR measurement and its status in Africa

“…Capillary blood microsampling techniques for iohexol determination have been successfully used in HPLC-UV and LC-MS/MS systems [26,27]. The most common way of sampling is with dried blood spots (DBS) using volumetric absorptive microsampling [28]. The small volume of blood needed is appealing for measuring GFR in children.…”