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Investigational Tests of Renal Function

Glomerular Filtration Rate
Radioisotopic Filtration Markers

The use of intravascularly injected radiolabeled compounds to define the GFR is potentially simpler and more precise than the methods discussed earlier because it involves detection of decay in radiation and avoids the necessity for a timed urine collection. These compounds include sodium iothalamate (125 I), diethylenetriamine penta-acetic acid (DTPA) (99m Tc), and ethylenediamine tetra-acetic acid (EDTA) (51 Cr). However, none of these compounds is inherently superior to inulin in its renal handling, the tests require great attention to detail and quality control, and there is the constant risk, albeit low, of radiation exposure.[11]

Total Renal Blood Flow
Flow Probes

Flow measurement by electromagnetic flow probes is based on the creation of a magnetic field around the circumference of the vessel. The field is disrupted by blood flow, and a voltage output proportional to blood velocity is generated. Ultrasonic flow probes use the Doppler technique in which high-frequency sound is transmitted across the lumen of the vessel. A shift in sound frequency is created by the movement of blood and is proportional to blood velocity.



Flow (mL/min) = Blood velocity (cm/min) × Area of vessel (cm2 )

Flow probe placement is invasive and requires direct surgical exposure of the renal arteries. Probes must be calibrated in vitro before and after measurements. However, they are generally very accurate.

Thermodilution Estimation of Renal Vein Effluent

Schaer and colleagues[24] used a double-lumen pigtail catheter with a thermistor placed in the renal vein of dogs under direct vision or fluoroscopy. RBF was calculated by thermodilution with cold saline, which allowed repeated measurements in conscious animals. The effect of the presence of the probe itself on RBF is unknown. A similar technique was used by Haywood and coworkers[25] to measure RBF for the assessment of renal oxygen delivery and consumption during septic shock in pigs.

Contrast Ultrasonography

Aronson and associates[26] attempted to measure RBF in vivo by contrast ultrasound. They injected sonicated albumin microspheres into the aorta of anesthetized dogs and then recorded simultaneous ultrasonographic images of the kidney and aorta and calculated RBF with a mathematical model. RBF was altered by means of a renal artery occluder or vasoactive drugs (dopamine or fenoldopam), and the results were compared with direct measurements by electromagnetic flow probe. Although the correlation between ultrasonography and flow probe measurements of RBF was reasonable (0.84), there was a large bias (in many cases greater than 200 mL/min) and variance. Ultrasonography tended to overestimate RBF, especially when cardiac output was changing. The authors concluded that this method allows estimation of trends in RBF and may be helpful in the qualitative assessment of regional distribution of blood flow between the renal cortex and medulla.

Intrarenal Blood Flow Distribution
Diffusible Gas Tracers

Considerable supposition about the intrarenal distribution of RBF within and between the renal cortex and medulla was based on studies using the radioactive gases 133 Xe and 85 Kr. The gases are injected into the renal artery, and radioactivity is counted externally. Renal radioactivity disappears faster the higher the blood flow, and flow is calculated mathematically from washout curves. In 1963, Thorburn and colleagues[27] extrapolated four monoexponential components from these curves, said to represent the outer renal cortex (zone I), juxtamedullary cortex (zone II), medulla (zone III), and perihilar fat (zone IV). Blood flow was greatest in zone I and progressively diminished through zones II to IV.

During the next decade, gas tracer studies such as those by Hollenberg and associates[28] suggested that ischemia and stress cause intrarenal redistribution of blood flow from zones I to II. Juxtamedullary nephrons are relatively


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salt retaining and have loops of Henle that penetrate the hypertonic medulla. Thus, this finding explained the retention of NaCl and edema observed during states of relative renal cortical hypoperfusion. However, the shortcomings of gas tracer techniques have generated skepticism about the validity of these studies.[29] The washout curves have not been matched to any specific anatomic area; 133 Xe itself decreases RBF, and the inert gases may diffuse out into the interstitium, especially in pathologic states.

Radioactive Microspheres

This terminal experimental procedure consists of the injection of radioactive microspheres—radiolabeled polystyrene beads 9 to 50 µm in diameter—into the central circulation. It is presumed that the microspheres are distributed to and within organs proportional to blood flow. The animal is then sacrificed, the organs are removed and dissected, and radioactivity is counted.

RBF = [Renal radioactivity (counts/min) × Cardiac output]/Total radioactivity of injected microspheres

Intrarenal localization of the microspheres truly represents regional blood flow. However, certain assumptions are made—that the injection itself does not interfere with renal hemodynamics and that all microspheres come to rest in the glomeruli without passing through the kidney or plugging arteries. It is also possible for this method to overestimate outer cortical blood flow because inner cortical afferent arterioles run at right angles to the interlobular arteries and microspheres may bypass through axial streaming.

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