Creatine and creatinine quantified using nuclear magnetic resonance: A method validation study and clinical associations between circulating creatine and fatigue in kidney transplant recipients

• Published in: Clinica chimica acta 2023-08, Vol.548, p.117517-117517, Article 117517
• Main Authors: Post, Adrian, Garcia, Erwin, Shalaurova, Irina, Matyus, Steven P., González-Delgado, Jessica M., Doorenbos, Caecilia S.E., van der Veen, Yvonne, Shah, Svati H., Kraus, William E., Kremer, Daan, Knobbe, Tim J., Bakker, Stephan J.L., Dullaart, Robin P.F., Connelly, Margery A.
• Format: Article
• Language: English
• Subjects: Creatine; Creatinine; Fatigue; Kidney transplantation; Nuclear magnetic resonance
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2023.117517

•We presented a validated method for the simultaneous measurement of circulating creatine and creatinine.•This assay offers accurate and efficient quantification, reducing technician time and instrument costs.•We measured plasma creatine and intramuscular creatine concentration in kidney transplant recipients.•Higher plasma creatine was associated with a lower total fatigue score.•Higher intramuscular creatine concentration was associated with a lower total fatigue score. A potential contributor to fatigue in kidney transplant recipients (KTR) may be impaired creatine homeostasis. We developed and validated a high-throughput NMR assay allowing for simultaneous measurement of circulating creatine and creatinine, and determined plasma creatine and estimated intramuscular creatine concentrations in KTRs, delineated their determinants and explored their associations with self-reported fatigue. An NMR assay was developed and validated for measurement of circulating creatinine and creatine concentrations. Plasma creatine and creatinine concentrations were measured in 618 KTR. Fatigue was assessed using the checklist individual strength. Associations of creatine parameters with fatigue was assessed using linear mixed effect models. The NMR-based assay had good sensitivity, precision and demonstrated linearity across a large range of values. Among KTR, the mean age was 56 ± 13 years, 62% were men and eGFR was 54 ± 18 ml/min/1.73 m2. Plasma creatine concentration was 27 [19–39] µmol/L. Estimated intramuscular creatine concentration was 27 ± 7 mmol/kg. Higher plasma creatine concentration and higher estimated intramuscular creatine concentration were independently associated with a lower total fatigue score and less motivation problems. An NMR method for measurement of circulating creatine and creatinine which offers the potential for accurate and efficient quantification was developed. The found associations suggest that improving creatine status may play a beneficial role in mitigating fatigue.