Measurement of arginine derivatives in pediatric patients with chronic kidney disease using high-performance liquid chromatography-tandem mass spectrometry

Sihe Wang 1 , 1 , Faye B. Vicente 2 , 2 , Alan Miller 3 , 3 , Ellen R. Brooks 4 , 4 , Heather E. Price 5 , 5  and Frederick A. Smith 6 , 6
  • 1 Department of Pathology and Laboratory Medicine, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • 2 Department of Pathology and Laboratory Medicine, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • 3 Department of Pathology and Laboratory Medicine, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • 4 Department of Kidney Diseases, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • 5 Department of Kidney Diseases, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • 6 Department of Pathology and Laboratory Medicine, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Abstract

Background: The arginine derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) interfere with endothelial nitric oxide synthesis. Plasma ADMA and SDMA have been shown to be risk factors for cardiovascular disease and/or kidney function deterioration in a variety of patient populations.

Methods: We developed a method to quantitatively measure arginine, ADMA, and SDMA using HPLC-tandem mass spectrometry. 13C6-L-Arginine was used as the internal standard, while the derivatives were separated on a silica column in less than 14 min. Plasma levels of ADMA, SDMA, and arginine were measured in children with stage II or III chronic kidney disease (CKD) and age- and gender-matched siblings.

Results: The chromatography exhibited no observable ion suppression in the patient specimens tested. There was no apparent carryover for any of the analytes. The assay was linear over 0.32–2.29, 0.23–4.43, and 1.00–303.89 μmol/L for ADMA, SDMA, and arginine, respectively. Plasma ADMA, SDMA, and arginine (mean±SD) were 1.10±0.35, 2.06±1.11, and 57.93±22.10 μmol/L for children with CKD, and 0.78±0.16, 0.71±0.23, and 65.29±21.30 μmol/L for the healthy siblings.

Conclusions: The method exhibited no observable ion suppression in the patient specimens tested and has an acceptably short analytical cycle time. Children with CKD had higher levels of ADMA and SDMA than the healthy siblings.

Clin Chem Lab Med 2007;45:1305–12.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.

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