In vivo measurements of kidney glomerular number and size in healthy and Os^/+ mice using MRI

The development of chronic kidney disease (CKD) is associated with the loss of functional nephrons. However, there are no methods to directly measure nephron number in living subjects. Thus, there are no methods to track the early stages of progressive CKD before changes in total renal function. In this work, we used cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) to enable measurements of glomerular number (N_glom) and apparent glomerular volume (aV_glom) in vivo in healthy wild-type (WT) mice (n = 4) and mice with oligosyndactylism (Os^/+; n = 4), a model of congenital renal hypoplasia leading to nephron reduction. We validated in vivo measurements of N_glom and aV_glom by highresolution ex vivo MRI. CFE-MRI measured a mean N_glom of 12,220 ± 2,028 and 6,848 ± 1,676 (means ± SD) for WT and Os^/+ mouse kidneys in vivo, respectively. N_glom measured in all mice in vivo using CFE-MRI varied by an average 15% from N_glom measured ex vivo in the same kidney (α = 0.05, P = 0.67). To confirm that CFE-MRI can also be used to track nephron endowment longitudinally, a WT mouse was imaged three times by CFE-MRI over 2 wk. Values of N_glom measured in vivo in the same kidney varied within ∼3%. Values of a_Vglom calculated from CFE-MRI in vivo were significantly different (∼15% on average, P < 0.01) from those measured ex vivo, warranting further investigation. This is the first report of direct measurements of N_glom and aV_glom in healthy and diseased mice in vivo.