MRI-based glomerular morphology and pathology in whole human kidneys

Scott Charles Beeman, Luise A Cullen-McEwen, Victor G Puelles Rodriguez, Min Zhang, Teresa Wu, Edwin Baldelomar, John P Dowling, Jennifer R Charlton, Michael Shepard Forbes, Amanda Ching Lih Ng, Qi-Zhu Wu, James A Armitage, Gary F Egan, John F Bertram, Kevin M Bennett

Research output: Contribution to journalArticleResearchpeer-review

65 Citations (Scopus)

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 functioning 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 functioning human kidneys. A fourth naive 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 3D 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 spectral analyses and may 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
Pages (from-to)F1381 - F1390
Number of pages10
JournalAmerican Journal of Physiology-Renal Physiology
Volume306
Issue number11
DOIs
Publication statusPublished - 2014

Cite this