Magnetic resonance imaging with hyperpolarized [1,4-(13)C2]fumarate allows detection of early renal acute tubular necrosis

Menna R Clatworthy, Mikko I Kettunen, De-En Hu, Rebeccah J Mathews, Timothy H Witney, Brett W C Kennedy, Sarah E Bohndiek, Ferdia A Gallagher, Lorna B Jarvis, Kenneth G C Smith, Kevin M Brindle

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Abstract

Acute kidney injury (AKI) is a common and important medical problem, affecting 10% of hospitalized patients, and it is associated with significant morbidity and mortality. The most frequent cause of AKI is acute tubular necrosis (ATN). Current imaging techniques and biomarkers do not allow ATN to be reliably differentiated from important differential diagnoses, such as acute glomerulonephritis (GN). We investigated whether (13)C magnetic resonance spectroscopic imaging (MRSI) might allow the noninvasive diagnosis of ATN. (13)C MRSI of hyperpolarized [1,4-(13)C(2)]fumarate and pyruvate was used in murine models of ATN and acute GN (NZM2410 mice with lupus nephritis). A significant increase in [1,4-(13)C(2)]malate signal was identified in the kidneys of mice with ATN early in the disease course before the onset of severe histological changes. No such increase in renal [1,4-(13)C(2)]malate was observed in mice with acute GN. The kidney [1-(13)C]pyruvate/[1-(13)C]lactate ratio showed substantial variability and was not significantly decreased in animals with ATN or increased in animals with GN. In conclusion, MRSI of hyperpolarized [1,4-(13)C(2)]fumarate allows the detection of early tubular necrosis and its distinction from glomerular inflammation in murine models. This technique may have the potential to identify a window of therapeutic opportunity in which emerging therapies might be applied to patients with ATN, reducing the need for acute dialysis with its attendant morbidity and cost.
Original languageEnglish
Pages (from-to)13374-13379
Number of pages6
JournalPNAS
Volume109
Issue number33
DOIs
Publication statusPublished - 14 Aug 2012

Keywords

  • animals
  • carbon isotopes
  • early diagnosis
  • folic acid
  • fumarates
  • humans
  • kidney
  • kidney tubular necrosis, acute
  • kinetics
  • lupus nephritis
  • magnetic resonance imaging
  • malates
  • mice
  • mice, inbred C57BL
  • pyruvic acid

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    Clatworthy, M. R., Kettunen, M. I., Hu, D-E., Mathews, R. J., Witney, T. H., Kennedy, B. W. C., Bohndiek, S. E., Gallagher, F. A., Jarvis, L. B., Smith, K. G. C., & Brindle, K. M. (2012). Magnetic resonance imaging with hyperpolarized [1,4-(13)C2]fumarate allows detection of early renal acute tubular necrosis. PNAS, 109(33), 13374-13379. https://doi.org/10.1073/pnas.1205539109