Volumetric microsampling for simultaneous remote immunosuppressant and kidney function monitoring in outpatient kidney transplant recipients
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society..
AIMS: Immunosuppressant and kidney function monitoring are crucial for kidney transplant recipient follow-up. Microsamples enable remote sampling and minimise patient burden as compared to conventional venous sampling at the clinic. We developed a liquid chromatography-tandem mass spectrometry assay to quantify tacrolimus, mycophenolic acid (MPA), creatinine and iohexol in dried blood spot (DBS), and volumetric absorptive microsample (VAMS) samples.
METHODS: The assay was successfully validated analytically for all analytes. Clinical validation was conducted by direct comparison of paired DBS, VAMS and venous reference samples from 25 kidney transplant recipients. Patients received iohexol 5-15 minutes before immunosuppressant intake and were sampled 0, 1, 2 and 3 hours thereafter, enabling tacrolimus and MPA area under the concentration-time curve (AUC) and creatinine-based and iohexol-based glomerular filtration rate (GFR) estimation. Method agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis and the percentages of values within 15-30% of the reference (P15 -P30 ) with a P20 acceptance threshold of 80%.
RESULTS: For DBS samples, method agreement was excellent for tacrolimus trough concentrations (n = 25, P15 = 92.0%) and AUCs (n = 25; P20 = 95.8%) and adequate for creatinine-based GFR trend monitoring (n = 25; P20 = 80%). DBS-based MPA AUC assessment showed suboptimal agreement (n = 16; P20 = 68.8%), but was considered acceptable given its P30 of 100%. The assay performed inadequately for DBS-based iohexol GFR determination (n = 24; P20 = 75%). The VAMS technique generally showed inferior performance, but can be considered for certain situations.
CONCLUSION: The assay was successfully validated for tacrolimus, MPA and creatinine quantification in DBS samples, enabling simultaneous remote kidney function trend monitoring and immunosuppressant therapeutic drug monitoring in kidney transplant recipients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
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| Enthalten in: |
British journal of clinical pharmacology - 88(2022), 11 vom: 07. Nov., Seite 4854-4869 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zwart, Tom C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.10.2022 Date Revised 31.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/bcp.15433 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM341927880 |
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| 100 | 1 | |a Zwart, Tom C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Volumetric microsampling for simultaneous remote immunosuppressant and kidney function monitoring in outpatient kidney transplant recipients |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 13.10.2022 | ||
| 500 | |a Date Revised 31.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. | ||
| 520 | |a AIMS: Immunosuppressant and kidney function monitoring are crucial for kidney transplant recipient follow-up. Microsamples enable remote sampling and minimise patient burden as compared to conventional venous sampling at the clinic. We developed a liquid chromatography-tandem mass spectrometry assay to quantify tacrolimus, mycophenolic acid (MPA), creatinine and iohexol in dried blood spot (DBS), and volumetric absorptive microsample (VAMS) samples | ||
| 520 | |a METHODS: The assay was successfully validated analytically for all analytes. Clinical validation was conducted by direct comparison of paired DBS, VAMS and venous reference samples from 25 kidney transplant recipients. Patients received iohexol 5-15 minutes before immunosuppressant intake and were sampled 0, 1, 2 and 3 hours thereafter, enabling tacrolimus and MPA area under the concentration-time curve (AUC) and creatinine-based and iohexol-based glomerular filtration rate (GFR) estimation. Method agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis and the percentages of values within 15-30% of the reference (P15 -P30 ) with a P20 acceptance threshold of 80% | ||
| 520 | |a RESULTS: For DBS samples, method agreement was excellent for tacrolimus trough concentrations (n = 25, P15 = 92.0%) and AUCs (n = 25; P20 = 95.8%) and adequate for creatinine-based GFR trend monitoring (n = 25; P20 = 80%). DBS-based MPA AUC assessment showed suboptimal agreement (n = 16; P20 = 68.8%), but was considered acceptable given its P30 of 100%. The assay performed inadequately for DBS-based iohexol GFR determination (n = 24; P20 = 75%). The VAMS technique generally showed inferior performance, but can be considered for certain situations | ||
| 520 | |a CONCLUSION: The assay was successfully validated for tacrolimus, MPA and creatinine quantification in DBS samples, enabling simultaneous remote kidney function trend monitoring and immunosuppressant therapeutic drug monitoring in kidney transplant recipients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a immunosuppressants | |
| 650 | 4 | |a kidney function | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a microsampling | |
| 650 | 4 | |a therapeutic drug monitoring | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Iohexol |2 NLM | |
| 650 | 7 | |a 4419T9MX03 |2 NLM | |
| 650 | 7 | |a Creatinine |2 NLM | |
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| 650 | 7 | |a Mycophenolic Acid |2 NLM | |
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| 650 | 7 | |a Tacrolimus |2 NLM | |
| 650 | 7 | |a WM0HAQ4WNM |2 NLM | |
| 700 | 1 | |a Metscher, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a van der Boog, Paul J M |e verfasserin |4 aut | |
| 700 | 1 | |a Swen, Jesse J |e verfasserin |4 aut | |
| 700 | 1 | |a de Fijter, Johan W |e verfasserin |4 aut | |
| 700 | 1 | |a Guchelaar, Henk-Jan |e verfasserin |4 aut | |
| 700 | 1 | |a de Vries, Aiko P J |e verfasserin |4 aut | |
| 700 | 1 | |a Moes, Dirk Jan A R |e verfasserin |4 aut | |
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