Mapping single nephron filtration in the isolated, perfused rat kidney using magnetic resonance imaging

The kidney has an extraordinary ability to maintain glomerular filtration despite natural fluctuations in blood pressure or nephron loss. This is partly due to local coordination between single nephron filtration and vascular perfusion. An improved understanding of the three-dimensional functional coordination between nephrons and the vasculature may provide a new perspective of the heterogeneity of kidney function and could inform targeted therapies and timed interventions to slow or prevent the progression of kidney disease. Here, we develop magnetic resonance imaging (MRI) tools to visualize the dynamics of single nephron function in three dimensions throughout the isolated perfused rat kidney. We used a intravenous slow perfusion of a glomerulus- targeted imaging tracer (cationized ferritin, CF), to map macromolecular dynamics and to identify glomeruli in 3D, followed by a bolus of a freely-filtered tracer, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), to map filtration kinetics. We observed a wide intra-kidney distribution of CF binding rates and snGFR between nephrons. snGFR and CF uptake rates did not vary significantly by distance from the kidney surface. snGFR varied from ~10 to ~100 nL/min throughout the kidney. Whole single kidney GFR (skGFR) was similar across all kidneys, despite differences in the distributions of estimated snGFR and glomerular number, indicating a robust adaptive regulation of individual nephrons to maintain constant skGFR in the presence of a natural variation in nephron number. This work provides a framework for studies of single nephron function in the whole isolated perfused kidney, and experiments of single nephron function in vivo using MRI.

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