Comprehensive Physiology Wiley Online Library
Home Browse Topics Latest Issue All Issues

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

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.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


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 ().

Figure 2. Figure 2.

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

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 ().

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 ().

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 ().

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 ().

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 ().

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 ().

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 ().

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 ().



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 ().



Figure 2.

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



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 ().



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 ().



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 ().



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 ().



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 ().



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 ().



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 ().



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 ().

References
 1. Addis T. Ratio between the urea content of the urine and of the blood after administration of large quantities of urea. J Urology 1: 263‐287, 1917.
 2. Allon M. Renal abnormalities in sickle cell disease. Arch Intern Med 150: 501‐504, 1990.
 3. Alving AS, Miller BF. A practical method for the measurement of glomerular filtration rate. Arch Int Med 66: 306‐318, 1940.
 4. Ames RP, Borkowski AJ, Sicinski AM, Laragh JH. Prolonged infusions of angiotensin II and norepinephrine and blood pressure, electrolyte balance, and aldosterone and cortisol secretion in normal man in cirrhosis with ascites. J Clin Invest 44: 1171‐1186. 1965.
 5. Aronson S, Wiencek JG, Feinstein SB, Heidenreich PA, Zaroff JG, Walker R, Roizen MF. Assessment of renal blood flow with contrast ultrasonography. Anesth Analg 76: 964‐970, 1993.
 6. Arthurson G, Wallenius G. The renal clearance of dextran of different molecular sizes in normal humans. Scand J Lab Clin Invest 16, 81‐86, 1964.
 7. Artunc F, Rossi C, Boss A. MRI to assess renal structure and function. Curr Opin Nephrol Hypertens 20: 669‐675, 2011.
 8. Artz NS, Sadowski EA, Wentland AL, Djamali A, Grist TM, Seo S, Fain SB. Reproducibility of renal perfusion mr imaging in native and transplanted kidneys using non‐contrast arterial spin labeling. J Magn Reson Imaging 33: 1414‐1421, 2011.
 9. Aukland K. Methods for measuring renal blood flow: Total flow and regional distribution. Annu Rev Physiol 42: 543‐555, 1980.
 10. Aukland K, Heyeraas Tonder K, Naess G. Capillary pressure in deep and superficial glomeruli of the rat kidney. Acta Physiol Scand 101: 418‐427, 1977.
 11. Badzynska B, Sadowski J. Opposed effects of prostaglandin E2 on perfusion of rat renal cortex and medulla: Interactions with the renin‐angiotensin system. Exp Physiol 93: 1292‐1302, 2008.
 12. Barnett HL. Renal physiology in infants and children, 1. Method for estimation of glomerular filtration rate. Proc Soc Exptl Biol Med 44: 654‐658, 1940.
 13. Bartoli CR, Okabe K, Akiyama I, Coull B, Godleski JJ. Repeat microsphere delivery for serial measurement of regional blood perfusion in the chronically instrumented, conscious canine. J Surg Res 145: 135‐141, 2008.
 14. Basak P, Jesmajian S. Nephrogenic systemic fibrosis: Current concepts. Indian J Dermatol 56: 59‐64, 2011.
 15. Berglund F. Renal clearance of inulin, polyfructosan‐S and a polyethylene glycol (PE6 1000) in the rat. Acta Physiol Scand 64: 238‐244, 1965.
 16. Bing J, Effersoe P. Comparative tests of the thiosulphate and creatinine clearances in rabbits and cats. Acta Physiol Scand 15: 231‐236, 1948.
 17. Bivona BJ, Park S, Harrison‐Bernard LM. Glomerular filtration rate determinations in conscious type II diabetic mice. Am J Physiol Renal Physiol 300: F618‐F625, 2011.
 18. Boron WF, Boulpaep EL. Urinary System. In: Medical Physiology: A Cellular and Molecular Approach. Philadelphia, PA: Elsevier Saunders, 2005. pp. 737‐876.
 19. Brezis M, Rosen S. Hypoxia of the renal medulla–its implications for disease. The New Eng J Med 332: 647‐655, 1995.
 20. Brion LP, Fleischman AR, McCarton C, Schwartz GJ. A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: Noninvasive assessment of body composition and growth. J Pediatr 109: 698‐707, 1986.
 21. Brun C. Thiosulfate as a measure of the glomerular filtration rate in normal and diseased human kidneys. Acta Physiol Scand Suppl 234: 63, 1949.
 22. Buckberg GD, Luck JC, Payne DB, Hoffman JI, Archie JP, Fixler DE. Some sources of error in measuring regional blood flow with radioactive microspheres. J Appl Physiol 31: 598‐604, 1971.
 23. Carmines PK, Morrison TK, Navar LG. Angiotensin II effects on microvascular diameters of in vitro blood‐perfused juxtamedullary nephrons. Am J Physiol 251: F610‐F618, 1986.
 24. Carter MK, Peters L. the clearance and phosphorylation of glucosamine by the mammalian kidney. Arch Intern Pharmacodyn 113: 406‐414, 1958.
 25. Carvlin MJ, Arger PH, Kundel HL, Axel L, Dougherty L, Kassab EA, Moore B. Use of gd‐dtpa and fast gradient‐echo and spin‐echo mr imaging to demonstrate renal function in the rabbit. Radiology 170: 705‐711, 1989.
 26. Casellas D, Carmines PK, Navar LG. Microvascular reactivity of in vitro blood perfused juxtamedullary nephrons from rats. Kidney Int 28: 752‐759, 1985.
 27. Casellas D, Navar LG. In vitro perfusion of juxtamedullary nephrons in rats. Am J Physiol 246: F349‐F358, 1984.
 28. Chantler C, Garnett ES, Parsons V, Veall N. glomerular filtration rate measurement in man by the single injection methods suing 51Cr‐EDTA. Clinical Sci 37: 169‐180, 1969.
 29. Chasis H, Jolloffe N, Smith HW. The action of phlorizin on the excretion of glucose, xylose, sucrose, creatinine and urea by man. J Clin Invest 12: 1083‐1090, 1933.
 30. Chen BC, Germano G, Huang SC, Hawkins RA, Hansen HW, Robert MJ, Buxton DB, Schelbert HR, Kurtz I, Phelps ME. A new noninvasive quantification of renal blood flow with n‐13 ammonia, dynamic positron emission tomography, and a two‐compartment model. J Am Soc Nephrol 3: 1295‐1306, 1992.
 31. Chesley LC. Renal excretion at low urine volumes and the mechanism of oliguria. J Clin Invest 17: 591‐597, 1938.
 32. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 16: 31‐41, 1976.
 33. Correia JA, Alpert NM, Buxton RB, Ackerman RH. Analysis of some errors in the measurement of oxygen extraction and oxygen consumption by the equilibrium inhalation method. J Cereb Blood Flow Metab 5: 591‐599, 1985.
 34. Coulam CH, Bouley DM, Sommer FG. Measurement of renal volumes with contrast‐enhanced mri. J Magn Reson Imaging 15: 174‐179, 2002.
 35. Cowley AW Jr, McCaa RE. Acute and chronic dose‐response relationships for angiotensin, aldosterone, and arterial pressure at varying levels of sodium intake. Circ Res 39: 788‐797, 1976.
 36. Crane J, Hakim N. The use of an implantable doppler flow probe in kidney transplantation: First report in the literature. Exp Clin Transplant 9: 118‐120, 2011.
 37. Creatinine – blood. MedlinePlus. US national Library of Medicine, NIH. URL is www.nim.nih.gov/medlineplus/ency/article/003475.htm.
 38. Cresseri A, Marro F. Renal B12 clearances in rabbits. Boll Soc Ital Biol Sper 33: 1662‐1664. 1957.
 39. Dahlborn K. Fluid balance in food‐deprived lactating goats drinking saline. Quarterly J Exp Physiol 72: 593‐600, 1987.
 40. Damkjaer M, Vafaee M, Moller ML, Braad PE, Petersen H, Hoilund‐Carlsen PF, Bie P. Renal cortical and medullary blood flow responses to altered no availability in humans. Am J Physiol 299: R1449‐R1455, 2010.
 41. Decking UK, Pai VM, Bennett E, Taylor JL, Fingas CD, Zanger K, Wen H, Balaban RS. High‐resolution imaging reveals a limit in spatial resolution of blood flow measurements by microspheres. Am J Physiol Heart Circ Physiol 287: H1132‐H1140, 2004
 42. DeClue JW, Guyton AW, Cowley AW Jr, Coleman TG, Norman RA, McCaa RE. Subpressor angiotensin infusion, renal sodium handling, and salt‐induced hypertension in the dog. Circ Res 43: 503‐512, 1978.
 43. deHaan MW, Kouwenhoven M, Kessels AG, van Engelshoven JM. Renal artery blood flow: Quantification with breath‐hold or respiratory triggered phase‐contrast MR imaging. Eur Radiol 10: 1133‐1137, 2000.
 44. Denk W, Strickler JH, Webb WW. Two‐photon laser scanning fluorescence microscopy. Science 248: 73‐76, 1990.
 45. Denton KM, Anderson WP, Sinniah R. Effects of angiotensin II on regional afferent and efferent arteriole dimensions and the glomerular pole. Am J Physiol Regul Integr Comp Physiol 279: R629‐R638, 2000.
 46. Denton KM, Fennessy PA, Alcorn D, Anderson WP. Morphometirc analysis of the actions of angiotensin II on renal arterioles and glomeruli. Am J Physiol 262: F367‐F372, 1992.
 47. Dobrucki LW, Sinusas AJ. Cardiovascular molecular imaging. Semin Nucl Med 35: 73‐81, 2005.
 48. Dworkin LD. Serum cystatin C as a marker of glomerular filtration rate. Current Op Neph Hypertension 10: 551‐553. 2001.
 49. Earle DR Jr, Berliner RW. A simplified clinical procedure for the measurement of glomerular filtration rate and renal plasma flow. Proc Soc Exptl Biol Med 62: 262‐264, 1946.
 50. Edwards RM. Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels. Am J Physiol 244: F526‐F534, 1983.
 51. Eisner C, Faulhaber‐Walter R, Wang Y, Leelahavanichkul A, Yuen PS, Mizel D, Star RA, Briggs JP, Levine M, Schnermann J. Major contribution of tubular secretion to creatinine clearance in mice. Kidney Int 77 (6): 519‐26, 2010.
 52. Eppel GA, Jacono DL, Shirai M, Umetani K, Evans RG, Pearson JT. Contrast angiography of the rat renal microcirculation in vivo using synchrotron radiation. Am J Physiol Renal Physiol 296: F1023‐F1031, 2009.
 53. Evans RG, Stevenson KM, Malpas SC, Fitzgerald SM, Shweta A, Tomoda F, Anderson WP. Chronic renal blood flow measurement in dogs by transit‐time ultrasound flowmetry. J pharmacol toxicol meth 38: 33‐39, 1997.
 54. Falbriard A, Zender R. Measurement of glomerular function by plasma decrease of a substance analogous to inulin (Polyfructosan‐S). Clinical importance and comparison with classical glomerular clearance. Nephron 72: 277‐294, 1964.
 55. Fenhammar J, Andersson A, Forestier J, Weitzberg E, Sollevi A, Hjelmqvist H, Frithiof R. Endothelin receptor a antagonism attenuates renal medullary blood flow impairment in endotoxemic pigs. PLoS One 6: e21534, 2011.
 56. Fisher NG, Christiansen JP, Leong‐Poi H, Jayaweera AR, Lindner JR, Kaul S. Myocardial and microcirculatory kinetics of br14, a novel third‐generation intravenous ultrasound contrast agent. J Am Coll Cardio 39: 530‐537, 2002.
 57. Friedman M, Byers SO. Clearance of allantoin in the rat and dog as a measure of glomerular filtration rates. Am J Physiol 151: 192‐197, 1947.
 58. Friedman M, Byers SO, Abraham PM. Renal clearance of allantoin as a measure of glomerular filtration rate. Am J Physiol 155: 278‐281, 1948.
 59. Gargiulo S, Greco A, Gramanzini M, Petretta MP, Ferro A, Larobina M, Panico M, Brunetti A, Cuocolo A. PET/CT imaging in mouse models of myocardial ischemia. J Biomed Biotechnol 2012: 541872, 2012.
 60. Gattone VH, Evan AP. Quantitative renal vascular casting in nephrology research. Scan Electron Microsc 253‐262, 1986.
 61. Gaudino M. kinetics of distribution of inulin between two body water compartments. Proc Soc Exptl Biol Med 70: 672‐674, 1949.
 62. Gault MH, Longerich LL, Harnett JD, Wesolowski C. Predicting glomerular function from adjusted serum creatinine. Nephron 62: 249‐256, 1992.
 63. Germano G, Chen BC, Huang SC, Gambhir SS, Hoffman EJ, Phelps ME. Use of the abdominal aorta for arterial input function determination in hepatic and renal pet studies. J Nucl Med 33: 613‐620, 1992.
 64. GFR MDRD calculator for adults. National Kidney Disease Education Program. United States: National Institutes of Health. http://www.nkdep.nih.gov/professionals/gfr_calculators/idms_con.htm.
 65. Gilman A, Philips FS, Koelle GS. The renal clearance of thiosulfate with observations on its volume distribution. Am J Physiol 146: 348‐357, 1946.
 66. Glenny RW, Bernard S, Brinkley M. Validation of fluorescent‐labeled microspheres for measurement of regional organ perfusion. J Appl Physiol 74: 2585‐2597, 1993.
 67. Glenny RW, McKinney S, Robertson HT. Spatial pattern of pulmonary blood flow distribution is stable over days. J Appl Physiol 82: 902‐907, 1997.
 68. Granger JP, Burnett JC Jr, Romero JC, Opgenorth TJ, Salazar J, Joyce M. Elevated levels of atrial natriuretic peptide during aldosterone escape. Am J Physiol 252: 878‐882, 1987
 69. Greco A, Petretta MP, Larobina M, Gargiulo S, Panico M, Nekolla SG, Esposito G, Petretta M, Brunetti A, Cuocolo A. Reproducibility and accuracy of non‐invasive measurement of infarctsize in mice with high‐resolution PET/CT. J Nucl Cardiol 19 (3): 492‐499, 2012.
 70. Green MA, Hutchins GD. Positron emission tomography (pet) assessment of renal perfusion. Semin Nephrol 31: 291‐299, 2011.
 71. Hall JE, Granger JP, Smith MJ Jr, Premen AJ. Role of renal hemodynamics and arterial pressure in aldosterone “escape”. Hypertension 6: I183‐I192, 1984.
 72. Hall JE, Guyton AC, Smith MJ Jr, Coleman TG. Blood pressure and renal function during chronic changes in sodium intake: Role of angiotensin. Am J Physiol 8: F271‐F280, 1980.
 73. Hall PM, Rolin H. Iothalamate clearance and its use in large‐scale clinical trials. Curr Opin Nephrol Hypertens 4: 510‐513, 1995.
 74. Hamburger A, Ryckewaert A, Duizend M, Argetny N. Sur une methode d'exploration separee des fonctions des glomerules et des tubules du rein. Presse Med 56: 721, 1948.
 75. Hansell P. Evaluation of methods for estimating renal medullary blood flow. Ren Physiol Biochem 15: 217‐230, 1992.
 76. Hansen PB, Castrop H, Briggs J, Schnermann J. Adenosine induces vasoconstriction through Gi‐dependent activation of phospholipase C in isolated perfused afferent arterioles of mice. J Am Soc Nephrol 14: 2457‐2465, 2003.
 77. Hansen PB, Poulsen CB, Walter S, Marcussen N, Cribbs LL, Skott O, Jensen BL. Functional importance of L‐ and p/q‐type voltage‐gated calcium channels in human renal vasculature. Hypertension 58: 464‐470, 2011.
 78. Harrison‐Bernard LM, Carmines PK. Impact of cyclooxygenase blockade on juxtamedullary microvascular responses to angiotensin II in rat kidney. Clin Exptl Pharm Physiol 22: 732‐738, 1995.
 79. Harrison‐Bernard LM, Cook AK, Oliverio MI, Coffman TM. Renal segmental microvascular responses to ANG II in AT1A receptor null mice. Am J Physiol Renal Physiol 284: F538‐F545, 2003.
 80. Harrison‐Bernard LM, Navar LG. Renal cortical and medullary microvascular blood flow autoregulation in rat. Kidney Int Suppl 57: S23‐S29, 1996.
 81. Hashimoto S, Yamada K, Kawata T, Mochizuki T, Schnermann J, Koike T. Abnormal autoregulation and tubuloglomerular feedback in prediabetic and diabetic OLETF rats. Am J Physiol Renal Physiol 296: F598‐F604, 2009.
 82. Hays RM, Levine SD. Pathophysiology of water metabolism. In: Edited by Brenner BM, Rector FC, editors. The Kidney (2nd ed). Philadelphia: WB Saunders Co., 1981, Vol. 1, Ch. 16 p. 810.
 83. Heiskanen T, Weber T, Grasbeck R. Determination of I131 hippuric acid renal clearances using single‐injection techniques. Scand J Clin Lab Invest 21: 211‐215, 1968.
 84. Heyeraas KJ, Aukland K. Interlobular arterial resistance: Influence of renal arterial pressure and angiotensin II. Kidney Int 31: 1291‐1298, 1987.
 85. Heymann MA, Payne BD, Hoffman JI, Rudolph AM. Blood flow measurements with radionuclide‐labeled particles. Prog Cardiovasc Dis 20: 55‐79, 1977
 86. Hiramatsu O, Goto M, Yada T, Kimura A, Chiba Y, Tachibana H, Ogasawara Y, Tsujioka K, Kajiya F. In vivo observations of the intramural arterioles and venules in beating canine hearts. J Physiol 509 (Pt 2): 619‐628, 1998.
 87. Holstein‐Rathlou NH, Sosnovtseva OV, Pavlov AN, Cupples WA, Sorensen CM, Marsh DJ. Nephron blood flow dynamics measured by laser speckle contrast imaging. Am J Physiol Renal Physiol 300: F319‐F329, 2011.
 88. Holtzman EJ, Bradley LM, Williams GH, Hollenberg NK. Kinetics of sodium homeostasis in rats: Rapid excretion and equilibration rates. Am J Physiol 254: R1001‐R1006, 1988.
 89. Imig JD, Falck JR, Gebremedhin D, Harder DR, Roman RJ. Elevated renovascular tone in young spontaneously hypertensive rats. Role of cytochrome P‐450. Hypertension 22: 357‐364, 1993.
 90. Ito S, Carretero OA. An in vitro approach to the study of macula densa‐mediated glomerular hemodynamics. Kidney Int 38: 1206‐1210, 1990.
 91. Janssen B, Debets J, Leenders P, Smits J. Chronic measurement of cardiac output in conscious mice. Am J Physiol 282: R928‐R935, 2002.
 92. Jones RA, Votaw JR, Salman K, Sharma P, Lurie C, Kalb B, Martin DR. Magnetic resonance imaging evaluation of renal structure and function related to disease: Technical review of image acquisition, postprocessing, and mathematical modeling steps. J Magn Reson Imaging 33: 1270‐1283, 2011.
 93. Juillard L, Janier MF, Fouque D, Lionnet M, Le Bars D, Cinotti L, Barthez P, Gharib C, Laville M. Renal blood flow measurement by positron emission tomography using 15o‐labeled water. Kidney Int 57: 2511‐2518, 2000.
 94. Kalyan A, Eppel GA, Anderson WP, Oliver JJ, Evans RG. Renal medullary interstitial infusion is a flawed technique for examining vasodilator mechanisms in anesthetized rabbits. J Pharm Toxicol Meth 47: 153‐159, 2002.
 95. Keith NM, Power MH, Peterson RD. the renal excretion of sucrose, xylose, urea and inorganic sulfates in normal man; comparison of simultaneous clearances. Am J Physiol 108: 221‐228, 1934.
 96. Khan MA, Islam MT, Castillo A, Majid DS. Attenuation of renal excretory responses to ANG II during inhibition of superoxide dismutase in anesthetized rats. Am J Physiol Renal Physiol 298: F401‐F407, 2010.
 97. Kimura K, Tojo A, Matsuoka H, Sugimoto T. Renal arteriolar diameters in spontaneously hypertensive rats: Vascular cast study. Hypertension 18: 101‐110, 1991.
 98. Kishimoto N, Mori Y, Nishiue T, Shibasaki Y, Iba O, Nose A, Uchiyama‐Tanaka Y, Masaki H, Matsubara H, Iwasaka T. Renal blood flow measurement with contrast‐enhanced harmonic ultrasonography: Evaluation of dopamine‐induced changes in renal cortical perfusion in humans. Clin Nephrol 59: 423‐428, 2003.
 99. Knox FG, Granger JP. Control of sodium excretion: An integrative approach. In: Windhager EE, editor. Handbook if Physiology. Renal Physiology, New York, NY: Oxford University Press. sect. 8, Ch. 21, p. 927‐967.
 100. Konerding MA. Scanning electron microscopy of corrosion casting in medicine. Scanning Microsc 5: 851‐865, 1991.
 101. Kornfeld M, Gutierrez AM, Gonzalez E, Salomonsson M, Persson AEG. Cell calcium concentration in glomerular afferent and efferent arterioles under the action of noradrenaline and angiotensin II. Acta Physiol Scand 151: 99‐105, 1994.
 102. Krier JD, Ritman EL, Bajzer Z, Romero JC, Lerman A, Lerman LO. Noninvasive measurement of concurrent single‐kidney perfusion, glomerular filtration, and tubular function. Am J Physiol Renal Physiol 281: F630‐F638, 2001.
 103. Kuiper JW, Versteilen AM, Niessen HW, Vaschetto RR, Sipkema P, Heijnen CJ, Groeneveld AB, Plotz FB. Production of endothelin‐1 and reduced blood flow in the rat kidney during lung‐injurious mechanical ventilation. Anesth Analg 107: 1276‐1283, 2008.
 104. Kuwa T, Cancio LC, Sondeen JL, Matylevich N, Jordan BS, McManus AT, Goodwin CW. Evaluation of renal cortical perfusion by noninvasive power doppler ultrasound during vascular occlusion and reperfusion. J Trauma 56: 618‐624, 2004.
 105. Lai EY, Wellstein A, Welch WJ, Wilcox CS. Superoxide modulates myogenic contractions of mouse afferent arterioles. Hypertension 58: 650‐656, 2011.
 106. Lambiotte C, Blanchard J, Graff S. Thiosulphate clearance in pregnancy. J Clin Invest 29: 1207‐1213, 1950.
 107. Laragh JH. The effect of potassium chloride on hyponatremia. J Clin Invest 33: 807‐818, 1954.
 108. Laragh JH, Ulick S, Januszewicz V, Deming QB, Kelly WG, Lieberman S. J Clin Invest 39: 1091‐1106, 1960.
 109. Launay‐Vacher V, Izzedine H, Deray G. Using the right MDRD equation. Kidney Int 66: 2089, 2004
 110. Ledoussal C, Lorenz JN, Nieman ML, Soleimani M, Schultheis PJ, Shull GE. Renal salt wasting in mice lacking NHE3 Na+/H+ exchanger but not in mice lacking NHE2. Am J Physiol Renal Physiol 281: F718‐F727, 2001.
 111. Lee VS, Rusinek H, Noz ME, Lee P, Raghavan M, Kramer EL. Dynamic three‐dimensional mr renography for the measurement of single kidney function: Initial experience. Radiology 227: 289‐294, 2003.
 112. Leiner T, de Haan MW, Nelemans PJ, van Engelshoven JM, Vasbinder GB. Contemporary imaging techniques for the diagnosis of renal artery stenosis. Europ Radiology 15: 2219‐2229, 2005.
 113. Lerman LO, Bell MR, Lahera V, Rumberger JA, Sheedy PF, II, Sanchez Fueyo A, Romero JC. Quantification of global and regional renal blood flow with electron beam computed tomography. Am J Hypertens 7: 829‐837, 1994.
 114. Lerman LO, Rodriguez‐Porcel M, Romero JC. The development of x‐ray imaging to study renal function. Kidney Int 55: 400‐416, 1999.
 115. Lerman LO, Schwartz RS, Grande JP, Sheedy PF, Romero JC. Noninvasive evaluation of a novel swine model of renal artery stenosis. J Am Soc Nephrol 10: 1455‐1465, 1999.
 116. Lerman LO, Taler SJ, Textor SC, Sheedy PF, II, Stanson AW, Romero JC. Computed tomography‐derived intrarenal blood flow in renovascular and essential hypertension. Kid Int 49: 846‐854, 1996.
 117. Levey AS, Bosch JP, Breyer LJ, Gren T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine; a new predictor equation. Modification of diet in Renal Disease Study Group. Ann Intern Med 130: 461‐470, 1999.
 118. Levey AS, Coresh J, Greene T. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145: 247‐254, 2006.
 119. Levey AS, Stevens LA, Schmid CH. A new equation to estimate glomerular filtration rate. Ann Intern Med 150: 604‐612, 2009.
 120. Levinsky NG, Berliner RW. Changes in composition of the ureter and bladder at low urine flow. Am J Physiol 196: 549‐553, 1959.
 121. Levinsky NG, Lieberthal W. Clearance techniques. In: Windhager E. editor. Handbook of Physiology. Renal Physiology. New York: Oxford University Press, 1992, sect. 8, pp. 227‐247.
 122. Li LP, Halter S, Prasad PV. Blood oxygen level‐dependent mr imaging of the kidneys. Magn Reson Imaging Clin N Am 16: 613‐625, 2008
 123. Lim K, Lombardo P, Schneider‐Kolsky M, Hilliard L, Denton KM, Black MJ. Induction of hyperglycemia in adult intrauterine growth‐restricted rats: Effects on renal function. Am J Physiol Renal Physiol 301: F288‐F294, 2011.
 124. Lindner JR, Song J, Jayaweera AR, Sklenar J, Kaul S. Microvascular rheology of definity microbubbles after intra‐arterial and intravenous administration. J Am Soc Echocardiogr 15: 396‐403, 2002.
 125. Liu X, Primak AN, Krier JD, Yu L, Lerman LO, McCollough CH. Renal perfusion and hemodynamics: Accurate in vivo determination at ct with a 10‐fold decrease in radiation dose and hypr noise reduction. Radiology 253: 98‐105, 2009.
 126. Lorenz JN. A practical guide to evaluating cardiovascular, renal and pulmonary function in mice. Am J Physiol 282: R1565‐R1582, 2002.
 127. Lorenz, JN. Micropuncture of the kidney: A primer on techniques. Compr Physiol 2: 621‐637, 2012.
 128. Lorenz JN, Gruenstein E. A simple, nonradioactive method for evaluating single‐nephron filtration rate using FITC‐inulin. Am J Physiol 276: F172‐F177, 1999
 129. Loutzenhiser R, Chilton L, Trottier G. Membrane potential measurements in renal afferent and efferent arterioles: Actions of angiotensin II. Am J Physiol 273: F307‐F314, 1997.
 130. Loutzenhiser R, Hayashi K, Epstein M. Atrial natriuretic peptide reverses afferent arteriolar vasoconstriction and potentiates efferent arteriolar vasoconstriction in the isolated perfused rat kidney. J Pharm Exp Therap 246: 522‐528, 1988.
 131. Loutzenhiser RD. In situ studies of renal arteriolar function using the in vitro perfused hydronephrotic rat kidney. Int Rev Exp Pathol 36: 36‐160, 1996.
 132. Lu S, Mattson DL, Roman RJ, Becker CG, Cowley AW, Jr. Assessment of changes in intrarenal blood flow in conscious rats using laser‐doppler flowmetry. Am J Physiol 264: F956‐F962, 1993.
 133. Lucidarme O, Kono Y, Corbeil J, Choi SH, Mattrey RF. Validation of ultrasound contrast destruction imaging for flow quantification. Ultrasound Med Biol 29: 1697‐1704, 2003.
 134. Ludemann L, Nafz B, Elsner F, Grosse‐Siestrup C, Meissler M, Kaufels N, Rehbein H, Persson PB, Michaely HJ, Lengsfeld P, Voth M, Gutberlet M. Absolute quantification of regional renal blood flow in swine by dynamic contrast‐enhanced magnetic resonance imaging using a blood pool contrast agent. Invest Radiol 44: 125‐134, 2009.
 135. Lundin B, Cooper TG, Meyer RA, Potchen EJ. Measurement of total and unilateral renal blood flow by oblique‐angle velocity‐encoded 2d‐cine magnetic resonance angiography. Magn Reson Imaging 11: 51‐59, 1993.
 136. Malvin RL, Wilde WS. Stop‐flow technique. In: Handbook of Physiology, sect. 8. Washington DC: Amer Physiol Soc, 1973, pp. 119‐128.
 137. Manning RD Jr, Hu L. Nitric oxide regulates renal hemodynamics and urinary sodium excretion in dogs. Hypertension 23: 619‐625, 1994.
 138. Maric‐Bilkan C, Flynn ER, Chade AR. Microvascular disease precedes the decline in renal function in the streptozotocin‐induced diabetic rat. Am J Physiol Renal Physiol 302: F308‐F315, 2012.
 139. Mattson DL. Kidney Function in Mice. Methods Mol Biol 573: 75‐94, 2009.
 140. Mattson DL, Krauski KR. Chronic sodium balance and blood pressure response to captopril in conscious mice. Hypertension 32: 923‐928, 1998.
 141. Marshall EK Jr. A comparison of the function of the glomerular and aglomerular kidney. Am J Physiol 94: 1‐10, 1930.
 142. Martirosian P, Boss A, Schraml C, Schwenzer NF, Graf H, Claussen CD, Schick F. Magnetic resonance perfusion imaging without contrast media. Eur J Nucl Med Mol Imaging. 37 (Suppl 1): S52‐S64, 2010.
 143. Martirosian P, Klose U, Mader I, Schick F. Fair true‐fisp perfusion imaging of the kidneys. Magn Reson Med 51: 353‐361, 2004.
 144. Mattson DL, Lu S‐H, Nakanishi K, Papanek PE, Cowley AW Jr. Effect of chronic renal medullary nitric oxide inhibition on blood pressure. Am J Physiol Heart Circ Physiol 266: H1918‐H1926, 1994.
 145. Matsuda H, Hayashi H, Arakawa K, Naitoh M, Kubota E, Honda M, Matsumoto A, Suzuki H, Yamamoto T, Kajiya F, Saruta T. Zonal heterogeneity in action of angiotensin‐converting enzyme inhibitor on renal microcirculation: Role of intrarenal bradykinin. J Am Soc Nephrol 10: 2272‐2282, 1999.
 146. Matsuda H, Hayashi K, Arakawa K, Kubota E, Honda M, Tokuyama H, Suzuki H, Yamamoto T, Kajiya F, Saruta T. Distinct modulation of superficial and juxtamedullary arterioles by prostaglandin in vivo. Hypertens Res 25: 901‐910, 2002.
 147. Matsushita K, Selvin E, Bash LD, Astor BC, Coresh J. “Risk implications of the new CKD Epidemiology Collaboration (CKD‐EPI) equation compared with the MDRD Study equation for estimated GFR: The Atherosclerosis Risk in Communities (ARIC) Study”. Am J Kidney Dis 55: 648‐59, 2010.
 148. Mattson DL, Lu S, Roman RJ, Cowley AW, Jr. Relationship between renal perfusion pressure and blood flow in different regions of the kidney. Am J Physiol 264: R578‐R583, 1993.
 149. Meneton P, Ichikawa I, Inagami T, Schnermann J. Renal physiology of the mouse. Am J Physiol Renal Physiol 476: F339‐F351, 2000.
 150. Meneton P, Schultheis PJ, Greeb J, Nieman ML, Liu LH, Clarke LL, Duffy JJ, Doetschman T, Lorenz JN, Shull GE. Increased sensitivity to K+ deprivation in colonic H,K‐ATPase‐deficient mice. J Clin Invest 101: 536‐542, 1998.
 151. Michaely HJ, Herrmann KA, Nael K, Oesingmann N, Reiser MF, Schoenberg SO. Functional renal imaging: Nonvascular renal disease. Abdom Imaging 32: 1‐16, 2007.
 152. Michaely HJ, Metzger L, Haneder S, Hansmann J, Schoenberg SO, Attenberger UI. Renal bold‐mri does not reflect renal function in chronic kidney disease. Kid Int 81: 684‐689, 2012
 153. Michell AR, Moss P, Hill R, Vincent IC, Noakes DE. The effect of pregnancy and sodium intake on water and electrolyte balance in sheep. Br Vet J 144: 147‐157, 1988.
 154. Miles KA. Measurement of tissue perfusion by dynamic computed tomography. Brit J Radiol 64: 409‐412, 1991.
 155. Miller BF, Winkler AW. The ferrocyanide clearance in man. J Clin Invest 15: 489‐492. 1936.
 156. Miyata N, Cowley AW, Jr. Renal intramedullary infusion of l‐arginine prevents reduction of medullary blood flow and hypertension in dahl salt‐sensitive rats. Hypertension 33: 446‐450, 1999.
 157. Moller EV, McIntosh F, Van Slyke DD. Studies of urea excretion. II. J Clin Invest 6: 427‐465, 1929.
 158. Molitoris BA, Sandoval RM. Intravital multiphoton microscopy of dynamic renal processes. Am J Physiol Renal Physiol 288: F1084‐F1089, 2005.
 159. Montet X, Ivancevic MK, Belenger J, Jorge‐Costa M, Pochon S, Pechere A, Terrier F, Vallee JP. Noninvasive measurement of absolute renal perfusion by contrast medium‐enhanced magnetic resonance imaging. Investi Radiol 38: 584‐592, 2003.
 160. Mule S, De Cesare A, Lucidarme O, Frouin F, Herment A. Regularized estimation of contrast agent attenuation to improve the imaging of microbubbles in small animal studies. Ultrasound in Med Biol 34: 938‐948, 2008.
 161. Murray RH, Luft FC, Bloch R, Weyman AE. Blood pressure responses to extremes of sodium intake in normal men. Proc Soc Exp Biol Med 159: 432‐436, 1978.
 162. Nakanishi K., Mattson DL, Cowley AW, Jr. Role of renal medullary blood flow in the development of L‐NAME hypertension in rats. Am J Physiol 268: R317‐R323, 1995.
 163. National Kidney Foundation. “K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification”. Am J Kidney Diseases 39 (Suppl 1): S1‐S266, 2002.
 164. Navar LG, Inscho EW, Majid DSA, Imig JD, Harrison‐Bernard LM, Mitchell KD. Paracrine regulation of the renal microcirculation. Physiol Rev 76: 425‐536, 1996.
 165. Newman EV, Bodley J, Winternitz J. the interrelationships of glomerular filtration rate (mannitol clearance), extracellular fluid volume, surface area of the body and plasma concentration of mannitol. Bill Johns Hopkins Hosp 75: 253‐268, 1944.
 166. Norman RA Jr, Enobakhare JA, DeClue JW, Douglas BH, Guyton AC. Arterial pressure‐urinary output relationship in hypertensive rats. Am J Physiol 234: R98‐R103, 1978.
 167. O'Connor PM. Renal oxygen delivery: Matching delivery to metabolic demand. Clin Exp Pharmacol Physiol 33: 961‐967, 2006.
 168. O'Connor PM, Kett MM, Anderson WP, Evans RG. Renal medullary tissue oxygenation is dependent on both cortical and medullary blood flow. Am J Physiol Renal Physiol 290: F688‐F694, 2006.
 169. Ofjord ES, Clausen G, Aukland K. Skimming of microspheres in vitro: Implications for measurement of intrarenal blood flow. Am J Physiol 241: H342‐H347, 1981.
 170. Pallone TL. Microdissected perfused vessels. Methods Mol Med 86: 443‐456, 2003.
 171. Pallone TL, Work J, Myers RL, Jamison RL. Transport of sodium and urea in outer medullary descending vasa recta. J Clin Invest 93: 212‐222, 1994.
 172. Pallone TL, Zhang Z, Rhinehart K. Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol 284: F253‐F266, 2003.
 173. Park JB, Olcott EW, Nishimura DG. Rapid measurement of time‐averaged blood flow using ungated spiral phase‐contrast. Magn Reson Med 49: 322‐328, 2003.
 174. Park JB, Santos JM, Hargreaves BA, Nayak KS, Sommer G, Hu BS, Nishimura DG. Rapid measurement of renal artery blood flow with ungated spiral phase‐contrast mri. J Magn Reson Imaging 21: 590‐595, 2005.
 175. Patel TY, Hovsepian DM, Duncan JR. Measurement of blood flow before and after embolization with use of fluorescent microspheres in an animal model. J Vasc Interv Radiol 17: 103‐111, 2006.
 176. Patzak A, Mrowka R, Storch E, Hocher B, Persson PB. Interaction of angiotensin II and nitric oxide in isolated perfused afferent arterioles of mice. J Am Soc Nephrol 12: 1122‐1127, 2001.
 177. Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function. New insights into old concepts. Clin Chem 38: 1933‐1953, 1992
 178. Peti‐Peterdi J. Multiphoton imaging of renal tissues in vitro. Am J Physiol Renal Physiol 288: F1079‐F1083, 2005.
 179. Peti‐Peterdi J, Morishima S, Bell PD, Okada Y. Two‐photon excitation fluorescence imaging of the living juxtaglomerular apparatus. Am J Physiol Renal Physiol 283: F197‐F201, 2002.
 180. Peti‐Peterdi J, Toma I, Sipos A, Vargas SL. Multiphoton imaging of renal regulatory mechanisms. Physiology (Bethesda) 24: 88‐96, 2009.
 181. Philips RW, Lewis LD, Knox KL. Alterations in body water turnover and distribution in neonatal calves with acute diarrhea. Ann NY Acad Sci 176: 231‐243, 1971.
 182. Pichler BJ, Wehrl HF, Kolb A, Judenhofer MS. Positron emission tomography/magnetic resonance imaging: The next generation of multimodality imaging? Semin Nucl Med 38: 199‐208, 2008.
 183. Pilkington LA, Binda R, deHaas JCM, Pitts RF. Intrarenal distribution of blood flow. Am J Physiol 208: 1107‐1113, 1965.
 184. Pitts RF, Lotspeich WD. Use of thiosulfate clearance as a measure of glomerular filtration rate in acidotic dogs. Proc Soc Exptl Biol Med 64: 224‐227, 1947.
 185. Prasad PV. Evaluation of intra‐renal oxygenation by bold mri. Nephron Clin Pract 103: c58‐c65, 2006
 186. Prasad PV, Edelman RR, Epstein FH. Noninvasive evaluation of intrarenal oxygenation with bold mri. Circulation 94: 3271‐3275, 1996.
 187. Prasad PV, Li LP, Halter S, Cabray J, Ye M, Batlle D. Evaluation of renal hypoxia in diabetic mice by bold mri. Investig Radiol 45: 819‐822, 2010.
 188. Prasad PV, Priatna A, Spokes K, Epstein FH. Changes in intrarenal oxygenation as evaluated by bold mri in a rat kidney model for radiocontrast nephropathy. J Magn Reson Imaging 13: 744‐747, 2001.
 189. Priatna A, Epstein FH, Spokes K, Prasad PV. Evaluation of changes in intrarenal oxygenation in rats using multiple gradient‐recalled echo (mgre) sequence. J Magn Reson Imaging 9: 842‐846, 1999
 190. Prinzen FW, Bassingthwaighte JB. Blood flow distributions by microsphere deposition methods. Cardiovasc Res 45: 13‐21, 2000.
 191. Prokop M. General principles of mdct. Eur J Radiol 45 (Suppl 1): S4‐S10, 2003.
 192. Qi Z, Whitt I, Mehta A, Jinn J, Zhao M, Harris RC, Fogo AB, Breyer MD. Serial determination of glomerular filtration rate in conscious mice using FITC‐inulin clearance. Am J Physiol Renal Physiol 286: F590‐F596, 2004.
 193. Quail AW, Cottee DB, White SW. Limitations of a pulsed Doppler velocimeter for blood flow measurement in small vessels. J Appl Physiol 75: 2745‐2754, 1993.
 194. Rao S, Verkman AS. Analysis of organ physiology in transgenic mice. Am J Physiol 279: 1‐18, 2000.
 195. Rehberg PB. Studies on kidney function. II. The rate of filtration and reabsorption in the human kidney. Biochem J 20: 447‐460, 1926.
 196. Relman AS, Levinsky NG. Clinical examination of renal function. In: MB Strauss, LG Welt, editors. Diseases of the Kidney, Boston: Little Brown, 1963, p. 80‐162.
 197. Ren Y, Garvin JL, Liu R, Carretero OA. Crosstalk between the connecting tubule and the afferent arteriole regulates renal microcirculation. Kidney Int 71: 1116‐1121, 2007.
 198. Ren Y, Garvin JL, Liu R, Carretero OA. Cross‐talk between arterioles and tubules in the kidney. Pediatr Nephrol 24: 31‐35, 2009.
 199. Rigalleau V, Lasseur C, Raffaitin C, Perlemoine C, Barthe N, Chauveau P, Combe C, Gin H. The Mayo Clinic Quadratic equation improves the prediction of glomerular filtration rate in diabetic subjects. Nephrol Dial Transplant 22 (3): 813‐818, 2007.
 200. Roman RJ, Carmines PK, Loutzenhiser R, Conger JD. Direct studies on the control of the renal microcirculation. J Am Soc Nephrol 2: 136‐149, 1991.
 201. Roman RJ, Cowley AW. Measurement of regional blood flow in the kidney using laser‐doppler flowmetry. Meth Mol Med 51: 407‐426, 2001.
 202. Ringgaard S, Christiansen T, Bak M, Pedersen EM, Stodkilde‐Jorgensen H, Flyvbjerg A. Measurement of renal vein blood flow in rats by high‐field magnetic resonance. Kidney Intl 52: 1359‐1363, 1997.
 203. Ritt M, Janka R, Schneider MP, Martirosian P, Hornegger J, Bautz W, Uder M, Schmieder RE. Measurement of kidney perfusion by magnetic resonance imaging: Comparison of mri with arterial spin labeling to para‐aminohippuric acid plasma clearance in male subjects with metabolic syndrome. Nephrol Dial Transplant 25: 1126‐1133, 2010.
 204. Rosivall L, Peti‐Peterdi J. Heterogeneity of the afferent arteriole–correlations between morphology and function. Nephrol Dial Transplant 21: 2703‐2707, 2006.
 205. Rostoker G, Andrivet P, Pham I, Griuncelli M, Adnot S. A modified Cockcroft‐Gault formula taking into account the body surface area gives a more accurate estimation of the glomerular filtration rate. J Nephrol 20: 576‐585, 2007.
 206. Rostoker G, Andrivet P, Pham I, Griuncelli M, Adnot S. Accuracy and limitations of equations for predicting the glomerular filtration rate during follow‐up of patients with non‐diabetic nephropathies. BMC Nephrol 708549, 2009.
 207. Rule AD, Larson TS, Bergsralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate; accuracy in good health and in chronic kidney disease. Ann Intern Med 141: 929‐937, 2004.
 208. Sarnak MJ, Katz R, Stehman‐Breen CO. Cystatin C concentration as a risk factor for heart failure in older adults. Ann Intern Med 142 (7): 497‐505, 2005.
 209. Schimmel C, Frazer D, Glenny RW. Extending fluorescent microsphere methods for regional organ blood flow to 13 simultaneous colors. Am J Physiol Heart Circ Physiol 280: H2496‐H2506, 2001
 210. Schmulder A, Gur E, Zaretski A. Eight‐year experience of the cook‐swartz doppler in free‐flap operations: Microsurgical and reexploration results with regard to a wide spectrum of surgeries. Microsurgery 31: 1‐6, 2011.
 211. Schoenberg SO, Just A, Bock M, Knopp MV, Persson PB, Kirchheim HR. Noninvasive analysis of renal artery blood flow dynamics with mr cine phase‐contrast flow measurements. Am J Physiol 272: H2477‐H2484, 1997.
 212. Schultheis PJ, Lorenz JN, Meneton P, Nieman ML, Riddle TM, Flagella M, Duffy JJ, Doetschman T, Miller ML, Shull GE. Phenotype resembling Gitelman's syndrome in mice lacking the apical Na+‐ Cl− cotransporter of the distal convoluted tubule. J Biol Chem 273: 29150‐29155, 1998.
 213. Schwartz GJ, Abraham AG, Furth SL. Optimizing iohexol plasma disappearance curves to measure the glomerular filtration rate in children with chronic kidney disease. Kidney Int 77: 65‐71, 2009.
 214. Schwartz GJ, Feld LG, Langford DJ. A simple estimate of glomerular filtration rate in full‐term infants during the first year of life. J Pediatr 104: 849‐54, 1984.
 215. Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58: 259‐63, 1976.
 216. Sehgal CM, Arger PH, Silver AC, Patton JA, Saunders HM, Bhattacharyya A, Bell CP. Renal blood flow changes induced with endothelin‐1 and fenoldopam mesylate at quantitative doppler us: Initial results in a canine study. Radiology 219: 419‐426, 2001.
 217. Shaffer CB, Critchfield FH, Carpenter CP. Renal excretion and volume distribution of some polyethylene glycols in the dog. Am J Physiol 152: 93‐99, 1948.
 218. Shirai M, Schwenke DO, Eppel GA, Evans RG, Edgley AJ, Tsuchimochi H, Umetani K, Pearson JT. Synchrotron‐based angiography for investigation of the regulation of vasomotor function in the microcirculation in vivo. Clin Exp Pharmacol Physiol 36: 107‐116, 2009.
 219. Shlipak MG, Sarnak MJ, Katz R. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med 352: 2049‐2060, 2005.
 220. Smith HW. The Kidney – Structure and Function in Health and Disease. New York: Oxford, University Press, 1951.
 221. Sourbron SP, Michaely HJ, Reiser MF, Schoenberg SO. Mri‐measurement of perfusion and glomerular filtration in the human kidney with a separable compartment model. Investi Radiol 43: 40‐48, 2008.
 222. Stanek KA, Smith TL, Murphy WR, Coleman TG. Hemodynamic disturbances in the rat as a function of the number of microspheres injected. Am J Physiol 245: H920‐H923, 1983.
 223.Stedman's Medical Dictionary. Copyright © 2006 Lippincott Williams & Wilkins.
 224. Steigerwalt S, Carretero OA, Beierwaltes WH. A stop‐flow study of intarenal effects of atrial natriuretic factor. Proc Soc Exptl Biol Med 182: 88‐94, 1986.
 225. Steinhausen M, Kucherer H, Parekh N, Weis S, Wiegman DL, Wilhelm KR. Angiotensin II control of the renal microcirculation: Effect of blockade by saralasin. Kidney Int 30: 56‐61, 1986.
 226. Steinhausen M, Snoei H, Parekh N, Baker R, Johnson PC. Hydronephrosis: A new method to visualize vas afferens, efferens, and glomerular network. Kidney Int 23: 794‐806, 1983.
 227. Steinhausen M, Sterzel RB, Fleming JT, Kühn R, Weis S. Acute and chronic effects of angiotensin II on the vessels of the split hydronephrotic kidney. Kidney Int Suppl 20: S64‐S73, 1987.
 228. Stevens LA, Coresh J, Smid CH, Feldman H, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce RD, Zhang YL, Green T, Levey AS. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: A pooled analysis of 3118 individuals with CKD. Am J Kidney Dis 51: 395‐406, 2008.
 229. Strauss MB, Lamdin E, Smith P, Bleifer DJ. Surfeit and deficit of sodium. AMA Arch Int Med 102: 527‐536, 2011.
 230. Sturgeon C, Ii ADS, Law WR. Rapid determination of glomerular filtration rate by single‐bolus inulin: A comparison of estimation analyses. J Appl Physiol 84: 2154‐2162, 1998.
 231. Sturgeon C, Sam AD, law WR. Rapid determination of glomerular filtration rate by single‐bolus inulin: A comparison of estimation analyses. J Appl Physiol 84: 2154‐2162, 1998.
 232. Sullivan JC, Wang B, Boesen EI, D'Angelo G, Pollock JS, Pollock DM. Novel use of ultrasound to examine regional blood flow in the mouse kidney. Am J Physiol Renal Physiol 297: F228‐F235, 2009.
 233. Szabo Z, Alachkar N, Xia J, Mathews WB, Rabb H. Molecular imaging of the kidneys. Sem Nucl Med 41: 20‐28, 2011.
 234. Szolar DH, Sakuma H, Higgins CB. Cardiovascular applications of magnetic resonance flow and velocity measurements. J Magn Reson Imaging 6: 78‐89, 1996.
 235. Takenaka T, Harrison‐Bernard LM, Inscho EW, Carmines PK, Navar LG. Autoregulation of afferent arteriolar blood flow in juxtamedullary nephrons. Am J Physiol 267: F879‐F887, 1994.
 236. Tamaki N, Rabito CA, Alpert NM, Yasuda T, Correia JA, Barlai‐Kovach M, Kanke M, Dragotakes SC, Strauss HW. Serial analysis of renal blood flow by positron tomography with rubidium‐82. Am J Physiol 251: H1024‐H1030, 1986.
 237. Teo BW, Xu H, Wang D, Li J, Sinha AK, Shuter B, Sethi S, Lee EJ. GFR estimating equations in a multiethnic Asian population. Am J Kidney Dis 58: 56‐63, 2011.
 238. Tessitore N, LoSchiavo C, Corgnati A, Previato G, Valvo E, Lupo A, Chiaramonte S, Messa P, D'Angelo A, Zatti M, Maschio G. 125I‐iothalamate and creatinine clearances in patients with chronic renal diseases. Nephron 24: 41‐45, 1979.
 239. Thein E, Raab S, Harris AG, Kleen M, Habler O, Meisner F, Messmer K. Comparison of regional blood flow values measured by radioactive and fluorescent microspheres. European surgical research. Europ Chirur Forsch 34: 215‐223, 2002.
 240. Titze J, Larina IM, Garib K, Kirsch KO, Maye A, Lang R, Gunga HK, Johanes B, Gochlen‐Koch H, Kim E. Monitoring of sodium balance during long‐term isolation of humans in a groundbased space station model. Human Physiol 29: 595‐605, 2003.
 241. Tønder KH, Aukland K. Glomerular capillary pressure in the rat. Validation of pressure measurement through corticotomy. Acta Physiol Scand 106: 93‐95, 1979.
 242. Vallee JP, Lazeyras F, Khan HG, Terrier F. Absolute renal blood flow quantification by dynamic mri and gd‐dtpa. Europ Radiol 10: 1245‐1252, 2000.
 243. Vallon V. In vivo studies of the genetically modified mouse kidney. Nephron Physiol 94: 1‐5, 2003
 244. Van Oosterhout MF, Willigers HM, Reneman RS, Prinzen FW. Fluorescent microspheres to measure organ perfusion: Validation of a simplified sample processing technique. Am J Physiol.; 269: H725‐H733, 1995.
 245. Van Slyke DD, Hiller A, Miller BF. The clearance, extraction percentage and estimated filtration of sodium ferrocyanide in the mammalian kidney. Am J Physiol 113: 611‐628, 1935.
 246. Wallinus G. Renal clearance of dextran as a measure of glomerular permeability. Acta Soc Med Ups Suppl 59: 1‐91, 1954.
 247. Wang E, Meier DJ, Sandoval RM, Von Hendy‐Willson VE, Presser BM, Bunch RM, Alloosh M, Sturek MS, Schwartz GJ, Molitoris BA. A portable fiberoptic ratiometric fluorescence analyzer provides rapid point‐of‐care determination of glomerular filtration rate in large animals. Kidney Int 81: 112‐117, 2012.
 248. Wang JJ, Hendrich KS, Jackson EK, Ildstad ST, Williams DS, Ho C. Perfusion quantitation in transplanted rat kidney by mri with arterial spin labeling. Kid Int 53: 1783‐1791, 1998.
 249. Wang YX, Betton G, Floettmann E, Fantham E, Ridgwell G. Imaging kidney in conscious rats with high‐frequency ultrasound and detection of two cases of unilateral congenital hydronephrosis. Ultrasound Med Biol 33: 483‐486, 2007.
 250. Warner L, Gomez SI, Bolterman R, Haas JA, Bentley MD, Lerman LO, Romero JC. Regional decreases in renal oxygenation during graded acute renal arterial stenosis: A case for renal ischemia. Am J Physiol 296: R67‐R71, 2009.
 251. Watschinger B, Kobinger I. Clearance tests with polyfructosan (Inutest). Wien Z Inn Med 45: 219‐28, 1964.
 252. Wen C, Li M, Whitworth JA. Validation of transonic small animal flowmeter for measurement of cardiac output and regional blood flow in the rat. J Cardio Pharm 27: 482‐486, 1996.
 253. Wentland AL, Artz NS, Fain SB, Grist TM, Djamali A, Sadowski EA. Mr measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: Noninvasive regional assessment of renal function. Nephrol Dial Transplant 27: 128‐135, 2011.
 254. Wei K, Le E, Bin JP, Coggins M, Thorpe J, Kaul S. Quantification of renal blood flow with contrast‐enhanced ultrasound. J Am Col Cardiol 37: 1135‐1140, 2001.
 255. Welch WJ, Deng X, Snellen H, Wilcox CS. Validation of miniature ultrasonic transit‐time flow probes for measurement of renal blood flow in rats. Am J Physiol 268: F175‐F178, 1995.
 256. Williams DS. Quantitative perfusion imaging using arterial spin labeling. Meth Mol Med 124: 151‐173, 2006.
 257. Williams DS, Zhang W, Koretsky AP, Adler S. Perfusion imaging of the rat kidney with mr. Radiology 190: 813‐818, 1994.
 258. Wu WC, Su MY, Chang CC, Tseng WY, Liu KL. Renal perfusion 3‐t mr imaging: A comparative study of arterial spin labeling and dynamic contrast‐enhanced techniques. Radiology 261: 845‐853, 2011.
 259. Xin‐Long P, Jing‐Xia X, Jian‐Yu L, Song W, Xin‐Kui T. A preliminary study of blood‐oxygen‐level‐dependent mri in patients with chronic kidney disease. Magn Reson Imaging 30: 330‐335, 2012.
 260. Yamamoto T, Hayashi K, Matsuda H, Kubota E, Tanaka H, Ogasawara Y, Nakamoto H, Suzuki H, Saruta T, Kajiya F. In vivo visualization of angiotensin II‐ and tubuloglomerular feedback‐mediated renal vasoconstriction. Kidney Int 60: 364‐369, 2001.
 261. Yamamoto T, Tada T, Brodsky SV, Tanaka H, Noiri E, Kajiya F, Goligorsky MS. Intravital videomicroscopy of peritubular capillaries in renal ischemia. Am J Physiol Renal Physiol 282: F1150‐F1155, 2002.
 262. Yamamoto T, Tomura Y, Tanaka H, Kajiya F. In vivo visualization of characteristics of renal microcirculation in hypertensive and diabetic rats. Am J Physiol Renal Physiol 281: F571‐F577, 2001.
 263. Yu W, Sandoval RM, Molitoris BA. Quantitative intravital microscopy using a generalized polarity concept for kidney studies. Am J Physiol Cell Physiol 289: C1197‐C1208, 2005.
 264. Yu W, Sandoval RM, Molitoris BA. Rapid determination of renal filtration fraction using an optical ratiometric imaging approach. Am J Physiol Renal Physiol 292: F1837‐F1880, 2007.
 265. Yuan BH, Robinette JB, Conger JD. Effect of angiotensin II and norepinephrine on isolated rat afferent and efferent arterioles. Am J Physiol 258: F741‐F750, 1990.
 266. Zhuang ZW, Gao L, Murakami M, Pearlman JD, Sackett TJ, Simons M, de Muinck ED. Arteriogenesis: Noninvasive quantification with multi‐detector row CT angiography and three‐dimensional volume rendering in rodents. Radiology 240: 698‐707, 2006.
 267. Zimmerhackl B, Parekh N, Kucherer H, Steinhausen M. Influence of systemically applied angiotensin II on the microcirculation of glomerular capillaries in the rat. Kidney Int 27: 17‐24, 1985.
 268. Zipfel WR, Williams RM, Webb WW. Nonlinear magic: Multiphoton microscopy in the biosciences. Nat Biotechnol 21: 1369‐1377, 2003.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

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