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Assessment of Renal Function; Clearance, the Renal Microcirculation, Renal Blood Flow, and Metabolic Balance

William H. Beierwaltes, Lisa M. Harrison‐Bernard, Jennifer C. Sullivan, David L. Mattson

10.1002/cphy.c120008

Source: Volume 3, Issue 1, January 2013

Published online: January 2013

Full Article on Wiley Online Library



Abstract

Historically, tools to assess renal function have been developed to investigate the physiology of the kidney in an experimental setting, and certain of these techniques have utility in evaluating renal function in the clinical setting. The following work will survey a spectrum of these tools, their applications and limitations in four general sections. The first is clearance, including evaluation of exogenous and endogenous markers for determining glomerular filtration rate, the adaptation of estimated glomerular filtration rate in the clinical arena, and additional clearance techniques to assess various other parameters of renal function. The second section deals with in vivo and in vitro approaches to the study of the renal microvasculature. This section surveys a number of experimental techniques including corticotomy, the hydronephrotic kidney, vascular casting, intravital charge coupled device videomicroscopy, multiphoton fluorescent microscopy, synchrotron‐based angiography, laser speckle contrast imaging, isolated renal microvessels, and the perfused juxtamedullary nephron microvasculature. The third section addresses in vivo and in vitro approaches to the study of renal blood flow. These include ultrasonic flowmetry, laser‐Doppler flowmetry, magnetic resonance imaging (MRI), phase contrast MRI, cine phase contrast MRI, dynamic contrast‐enhanced MRI, blood oxygen level dependent MRI, arterial spin labeling MRI, x‐ray computed tomography, and positron emission tomography. The final section addresses the methodologies of metabolic balance studies. These are described for humans, large experimental animals as well as for rodents. Overall, the various in vitro and in vivo topics and applications to evaluate renal function should provide a guide for the investigator or physician to understand and to implement the techniques in the laboratory or clinic setting. © 2013 American Physiological Society. Compr Physiol 3:165‐200, 2013.

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Figure 1. Figure 1.

In vivo study of the rat hydronephrotic kidney. (A) The kidney is exposed and cut with a cautery along the greater curvature, (B) spread out as a thin sheet, sutured to a chamber, and (C) mounted to a microscope stage for transillumination videomicroscopy (225).
Figure 2. Figure 2.

Videophotomicrograph taken from a television screen demonstrating glomeruli, renal arteries, and arterioles on the surface of a hydronephrotic kidney (225).
Figure 3. Figure 3.

Scanning electron micrograph of a renal vascular cast. The image depicts rat glomerular capillary tufts and afferent and efferent arterioles. The lines marked on the arterioles are the points at which luminal diameters and length measurements are taken. Scale bar = 100 μm (4400).
Figure 4. Figure 4.

Intravital needle‐type charge‐coupled device (CCD) videomicroscopic system. The microscope system for visualization of the canine glomerular microcirculation consists of a pencil‐probe videomicroscope with a CCD camera, a camera body containing a cone‐shaped lens, light guide, light source, monitor, videocassette recorder, and a computer for image analysis (261).
Figure 5. Figure 5.

Visualization of various glomerular and juxtaglomerular apparatus structures in situ using multiphoton confocal laser scanning fluorescence microscopy. (A) Glomerulus perfused through the afferent arteriole (AA) with attached cortical thick ascending limb (cTAL) and macula densa (MD). Tissue was stained with TMA‐DPH. Note the dilation of Bowman's capsule (CAP) and exit of glomerular filtrate via the proximal tubule (PT). (B) Calcium image of the double‐perfused AA and cTAL containing the MD. Tissue was loaded with indo 1. G, glomerulus; EA, efferent arteriole. Scale bar = 10 μm (178).
Figure 6. Figure 6.

Technique for the isolation of the afferent arteriole with the attached macula densa containing thick ascending limb of the loop of Henle. Schematic representation of the pipette arrangement used for perfusion of an afferent arteriole (Af‐Art) and attached macula densa (MD). TALH, thick ascending limb of Henle's loop; GL, glomerulus; DCT, distal convoluted tubule; Ef‐Art, efferent arteriole; Hold‐Pip, holding pipette; Perf‐Pip, perfusion pipette; Exch‐Pip, exchange pipette; Pre‐Pip, pressure pipette (89).
Figure 7. Figure 7.

Simultaneous perfusion of microdissected rabbit afferent arterioles with adherent cortical connecting tubule (CNT). (A) Schematic representation of the perfusion system. (B) Picture of the simultaneous perfusion of a microdissected rabbit Af‐Art and attached CNT. Abbreviations as in Figure 6 (196).
Figure 8. Figure 8.

Mouse in vitro blood perfused juxtamedullary nephron. (A) Photograph of the mouse kidney during the dissection procedure. The kidney is perfused via a 25G needle. The pelvic mucosa is reflected up and held in place in pins revealing the underlying juxtamedullary nephrons. (B) Photograph of the mouse kidney on the stage of the videomicroscope. The chamber is warmed and the kidney is superfused with solutions. (C) Digital image captured from the video monitor of a mouse blood perfused afferent arteriole. The arrows demarcate the inside luminal borders. Scale bar = 15 μm (78).
Figure 9. Figure 9.

(A) Representative magnetic resonance imaging (MRI) images of a mouse kidney. Panel B includes an overlay to indicate renal anatomy including the renal cortex, outer medulla (OM), and inner medulla (IM). MRI imaging was performed using a Bruker Biospin 7T horizontal bore scanner with T2W resolution = 67 × 67 × 500 micron3.
Figure 10. Figure 10.

Representative ultrasound images of a mouse kidney. Panel A is a B‐mode image of a mouse kidney. Panel B includes an overlay to indicate renal anatomy including the renal cortex, outer medulla (OM), and inner medulla (IM). Ultrasound imaging was performed using the Vevo 770 system (VisualSonics Inc, Toronto, Canada) with a RMV‐706 scanhead. The RMV‐706 scanhead is a 40 MHz scanhead with a 6 mm focal length and lateral and axial resolutions of 68.2 and 38.5 μm, respectively.
Figure 11. Figure 11.

(A) Representative computed tomography images of a pig kidney. Panel B includes an overlay to indicate renal anatomy including the renal cortex, outer medulla (OM), and inner medulla (IM). For these studies, perfusion scans were performed at 80 kV and 160 mA in sequential mode, with 20 × 1.2 collimation and 0 mm table feed. Using a 0.5 s gantry rotation time and a 0.36 s partial reconstruction, 90 multiscan exposures were acquired during a 0.5 s cycle, followed by 70 scans during a 2 s cycle, bringing the total scanning time to about 3 min. For each exposure, four contiguous 6 mm images were acquired and reconstructed.
Figure 12. Figure 12.

Daily sodium intake, sodium excretion rate, and sodium balance in conscious dogs infused intravenously with the nitric oxide synthase inhibitor NG‐nitro‐l‐arginine methyl ester (L‐NAME). * indicates P < 0.05 compared with the average control value. Permission yet not received (136).
Figure 13. Figure 13.

An individual mouse housed in plastic metabolic cage equipped with funnel for urine collection. Ingested food and water are quantified for determination of daily balance.
Figure 14. Figure 14.

Mean arterial blood pressure, sodium intake and output, and daily sodium balance in chronically instrumented, conscious mice as sodium intake was increased from approximately 150 to 900 μEq/d by intravenous infusion of isotonic saline. Measurements were taken on nine consecutive days; the sodium intake. Daily sodium intake was increased from approximately 150 to 500 after the third day of collection and from approximately 500 to 900 after the sixth day. * indicates output significantly different from the intake for that day (P < 0.05). Permission yet not received (139).


Figure 1.

In vivo study of the rat hydronephrotic kidney. (A) The kidney is exposed and cut with a cautery along the greater curvature, (B) spread out as a thin sheet, sutured to a chamber, and (C) mounted to a microscope stage for transillumination videomicroscopy (225).



Figure 2.

Videophotomicrograph taken from a television screen demonstrating glomeruli, renal arteries, and arterioles on the surface of a hydronephrotic kidney (225).



Figure 3.

Scanning electron micrograph of a renal vascular cast. The image depicts rat glomerular capillary tufts and afferent and efferent arterioles. The lines marked on the arterioles are the points at which luminal diameters and length measurements are taken. Scale bar = 100 μm (4400).



Figure 4.

Intravital needle‐type charge‐coupled device (CCD) videomicroscopic system. The microscope system for visualization of the canine glomerular microcirculation consists of a pencil‐probe videomicroscope with a CCD camera, a camera body containing a cone‐shaped lens, light guide, light source, monitor, videocassette recorder, and a computer for image analysis (261).



Figure 5.

Visualization of various glomerular and juxtaglomerular apparatus structures in situ using multiphoton confocal laser scanning fluorescence microscopy. (A) Glomerulus perfused through the afferent arteriole (AA) with attached cortical thick ascending limb (cTAL) and macula densa (MD). Tissue was stained with TMA‐DPH. Note the dilation of Bowman's capsule (CAP) and exit of glomerular filtrate via the proximal tubule (PT). (B) Calcium image of the double‐perfused AA and cTAL containing the MD. Tissue was loaded with indo 1. G, glomerulus; EA, efferent arteriole. Scale bar = 10 μm (178).



Figure 6.

Technique for the isolation of the afferent arteriole with the attached macula densa containing thick ascending limb of the loop of Henle. Schematic representation of the pipette arrangement used for perfusion of an afferent arteriole (Af‐Art) and attached macula densa (MD). TALH, thick ascending limb of Henle's loop; GL, glomerulus; DCT, distal convoluted tubule; Ef‐Art, efferent arteriole; Hold‐Pip, holding pipette; Perf‐Pip, perfusion pipette; Exch‐Pip, exchange pipette; Pre‐Pip, pressure pipette (89).



Figure 7.

Simultaneous perfusion of microdissected rabbit afferent arterioles with adherent cortical connecting tubule (CNT). (A) Schematic representation of the perfusion system. (B) Picture of the simultaneous perfusion of a microdissected rabbit Af‐Art and attached CNT. Abbreviations as in Figure 6 (196).



Figure 8.

Mouse in vitro blood perfused juxtamedullary nephron. (A) Photograph of the mouse kidney during the dissection procedure. The kidney is perfused via a 25G needle. The pelvic mucosa is reflected up and held in place in pins revealing the underlying juxtamedullary nephrons. (B) Photograph of the mouse kidney on the stage of the videomicroscope. The chamber is warmed and the kidney is superfused with solutions. (C) Digital image captured from the video monitor of a mouse blood perfused afferent arteriole. The arrows demarcate the inside luminal borders. Scale bar = 15 μm (78).



Figure 9.

(A) Representative magnetic resonance imaging (MRI) images of a mouse kidney. Panel B includes an overlay to indicate renal anatomy including the renal cortex, outer medulla (OM), and inner medulla (IM). MRI imaging was performed using a Bruker Biospin 7T horizontal bore scanner with T2W resolution = 67 × 67 × 500 micron3.



Figure 10.

Representative ultrasound images of a mouse kidney. Panel A is a B‐mode image of a mouse kidney. Panel B includes an overlay to indicate renal anatomy including the renal cortex, outer medulla (OM), and inner medulla (IM). Ultrasound imaging was performed using the Vevo 770 system (VisualSonics Inc, Toronto, Canada) with a RMV‐706 scanhead. The RMV‐706 scanhead is a 40 MHz scanhead with a 6 mm focal length and lateral and axial resolutions of 68.2 and 38.5 μm, respectively.



Figure 11.

(A) Representative computed tomography images of a pig kidney. Panel B includes an overlay to indicate renal anatomy including the renal cortex, outer medulla (OM), and inner medulla (IM). For these studies, perfusion scans were performed at 80 kV and 160 mA in sequential mode, with 20 × 1.2 collimation and 0 mm table feed. Using a 0.5 s gantry rotation time and a 0.36 s partial reconstruction, 90 multiscan exposures were acquired during a 0.5 s cycle, followed by 70 scans during a 2 s cycle, bringing the total scanning time to about 3 min. For each exposure, four contiguous 6 mm images were acquired and reconstructed.



Figure 12.

Daily sodium intake, sodium excretion rate, and sodium balance in conscious dogs infused intravenously with the nitric oxide synthase inhibitor NG‐nitro‐l‐arginine methyl ester (L‐NAME). * indicates P < 0.05 compared with the average control value. Permission yet not received (136).



Figure 13.

An individual mouse housed in plastic metabolic cage equipped with funnel for urine collection. Ingested food and water are quantified for determination of daily balance.



Figure 14.

Mean arterial blood pressure, sodium intake and output, and daily sodium balance in chronically instrumented, conscious mice as sodium intake was increased from approximately 150 to 900 μEq/d by intravenous infusion of isotonic saline. Measurements were taken on nine consecutive days; the sodium intake. Daily sodium intake was increased from approximately 150 to 500 after the third day of collection and from approximately 500 to 900 after the sixth day. * indicates output significantly different from the intake for that day (P < 0.05). Permission yet not received (139).

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Article Title: Assessment of Renal Function; Clearance, the Renal Microcirculation, Renal Blood Flow, and Metabolic Balance
 

How to Cite

William H. Beierwaltes, Lisa M. Harrison‐Bernard, Jennifer C. Sullivan, David L. Mattson. Assessment of Renal Function; Clearance, the Renal Microcirculation, Renal Blood Flow, and Metabolic Balance. Compr Physiol 2013, 3: 165-200. doi: 10.1002/cphy.c120008