Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri.
Division of Nephrology, Department of Pediatrics, University of Virginia, Charlottesville, Virginia.
Am J Physiol Renal Physiol. 2022 Nov 1;323(5):F602-F611. doi: 10.1152/ajprenal.00103.2022. Epub 2022 Sep 1.
The kidney has an extraordinary ability to maintain glomerular filtration despite natural fluctuations in blood pressure and nephron loss. This is partly due to local coordination between single-nephron filtration and vascular perfusion. An improved understanding of the three-dimensional (3-D) 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 developed magnetic resonance imaging (MRI) tools to visualize single-nephron function in 3-D throughout the isolated perfused rat kidney. We used an intravenous slow perfusion of a glomerulus-targeted imaging tracer [cationized ferritin (CF)] to map macromolecular dynamics and to identify glomeruli in 3-D, followed by a bolus of a freely filtered tracer (gadolinium diethylenetriamine penta-acetic acid) to map filtration kinetics. There was a wide intrakidney distribution of CF binding rates and estimated single-nephron glomerular filtration rate (eSNGFR) between nephrons. eSNGFR and CF uptake rates did not vary significantly by distance from the kidney surface. eSNGFR varied from ∼10 to ∼100 nL/min throughout the kidney. Whole single-kidney GFR was similar across all kidneys, despite differences in the distributions eSNGFR of and glomerular number, indicating a robust adaptive regulation of individual nephrons to maintain constant single-kidney GFR in the presence of a natural variation in nephron number. This work provides a framework for future studies of single-nephron function in the whole isolated perfused kidney and experiments of single-nephron function in vivo using MRI. We report MRI tools to measure and map single-nephron function in the isolated, perfused rat kidney. We used imaging tracers to identify nephrons throughout the kidney and to measure the delivery and filtration of the tracers at the location of the glomeruli. With this technique, we directly measured physiological parameters including estimated single-nephron glomerular filtration rate throughout the kidney. This work provides a foundation for new studies to simultaneously map the function of large numbers of nephrons.
肾脏具有维持肾小球滤过的非凡能力，尽管血压和肾单位损失会自然波动。这在一定程度上是由于单个肾单位滤过和血管灌注之间的局部协调。对肾单位和血管之间的三维（3-D）功能协调的更好理解可能为肾脏功能的异质性提供新的视角，并为靶向治疗和定时干预提供信息，以减缓或预防肾脏疾病的进展。在这里，我们开发了磁共振成像（MRI）工具，以在整个分离灌注的大鼠肾脏中可视化单个肾单位的 3-D 功能。我们使用静脉内缓慢灌注肾小球靶向成像示踪剂[阳离子化铁蛋白（CF）]来绘制大分子动力学图，并在 3-D 中识别肾小球，然后再用自由过滤示踪剂（钆二乙三胺五乙酸）进行快速注射以绘制滤过动力学图。在肾内，CF 结合率和估计的单个肾单位肾小球滤过率（eSNGFR）在肾单位之间存在广泛的分布。eSNGFR 和 CF 摄取率与距肾脏表面的距离没有明显变化。eSNGFR 在整个肾脏中变化范围从约 10 到约 100 nL/min。尽管肾小球数量和 eSNGFR 的分布存在差异，但整个肾脏的单个肾脏 GFR 相似，这表明单个肾单位具有强大的适应性调节能力，可在肾单位数量自然变化的情况下维持单个肾脏 GFR 的恒定。这项工作为未来在整个分离灌注的肾脏中研究单个肾单位功能以及使用 MRI 在体内研究单个肾单位功能提供了框架。我们报告了用于测量和绘制分离灌注大鼠肾脏中单个肾单位功能的 MRI 工具。我们使用成像示踪剂在整个肾脏中识别肾单位，并测量示踪剂在肾小球位置的输送和过滤。通过这项技术，我们直接测量了包括整个肾脏中估计的单个肾单位肾小球滤过率在内的生理参数。这项工作为同时绘制大量肾单位功能的新研究提供了基础。
