MRI-based glomerular morphology and pathology in whole human kidneys

Scott C. Beeman, Luise A. Cullen-McEwen, Victor G. Puelles, Min Zhang, Teresa Wu, Edwin J. Baldelomar, John Dowling, Jennifer R. Charlton, Michael S. Forbes, Amanda Ng, Qi Zhu Wu, James A. Armitage, Gary F. Egan, John F. Bertram, Kevin M. Bennett

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Nephron number (Nglom) and size (Vglom) are correlated with risk for chronic cardiovascular and kidney disease and may be predictive of renal allograft viability. Unfortunately, there are no techniques to assess Nglom and Vglom in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure Nglom and Vglom in viable human kidneys donated to science. The kidneys were obtained from patients with varying levels of cardiovascular and renal disease. CF was intravenously injected into three viable human kidneys. A fourth control kidney was perfused with saline. After fixation, immunofluorescence and electron microscopy confirmed binding of CF to the glomerulus. The intact kidneys were imaged with three-dimensional MRI and CF-labeled glomeruli appeared as punctate spots. Custom software identified, counted, and measured the apparent volumes of CF-labeled glomeruli, with an ~6% false positive rate. These measurements were comparable to stereological estimates. The MRI-based technique yielded a novel whole kidney distribution of glomerular volumes. Histopathology demonstrated that the distribution of CF-labeled glomeruli may be predictive of glomerular and vascular disease. Variations in CF distribution were quantified using image texture analyses, which be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.

Original languageEnglish (US)
Pages (from-to)F1381-F1390
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number11
DOIs
StatePublished - Jun 1 2014

Keywords

  • Cationized ferritin
  • Chronic kidney disease
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Physiology
  • Urology

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  • Cite this

    Beeman, S. C., Cullen-McEwen, L. A., Puelles, V. G., Zhang, M., Wu, T., Baldelomar, E. J., Dowling, J., Charlton, J. R., Forbes, M. S., Ng, A., Wu, Q. Z., Armitage, J. A., Egan, G. F., Bertram, J. F., & Bennett, K. M. (2014). MRI-based glomerular morphology and pathology in whole human kidneys. American Journal of Physiology - Renal Physiology, 306(11), F1381-F1390. https://doi.org/10.1152/ajprenal.00092.2014