Renal Clearance

The concept of renal clearance is based on the Fick principle (i.e., mass balance or conservation of mass). Fig. 3.1 illustrates the various factors required to describe the mass balance relationships of a kidney. For substances that are neither synthesized nor metabolized by the kidney, the renal artery is the single input source to the kidney, whereas the renal vein and ureter constitute the two output routes. In other words, if a substance is neither synthesized nor metabolized by the kidney, the amount entering the renal circulation via the renal artery may only exit this circulation via the renal vein (i.e., the unfiltered fraction plus any filtered amount that is subsequently reabsorbed back into the blood) or the ureter (the combined filtered and secretion fractions less any tubular reabsorption). The following equation defines the mass balance relationship:

Mass balance relationships for the kidney. <SPAN role=presentation tabIndex=0 id=MathJax-Element-5-Frame class=MathJax style="POSITION: relative" data-mathml='Pxa’>PaxPxa
P x a
and <SPAN role=presentation tabIndex=0 id=MathJax-Element-6-Frame class=MathJax style="POSITION: relative" data-mathml='Pxv’>PvxPxv
P x v
, concentrations of substance x in the renal artery and renal vein plasma, respectively; RPF ^a and RPF ^v , renal plasma flow rates in the artery and vein, respectively; U _x , concentration of x in the urine; <SPAN role=presentation tabIndex=0 id=MathJax-Element-7-Frame class=MathJax style="POSITION: relative" data-mathml='V˙’>?˙V˙
V ˙
, urine flow rate.

This relationship permits the quantification of the amount of x excreted in the urine versus the amount returned to the systemic circulation in the renal venous blood. Therefore for any substance that is neither synthesized nor metabolized by the kidneys, the amount that enters the kidneys is equal to the amount that leaves the kidneys in the urine plus the amount that leaves the kidneys in the renal venous blood.

The principle of renal clearance emphasizes the excretory function of the kidneys; it considers only the rate at which a substance is excreted into the urine and not its rate of return to the systemic circulation in the renal vein. Therefore in terms of mass balance ( Eq. 3.1 ), the urinary excretion rate of x ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-8-Frame class=MathJax style="POSITION: relative" data-mathml='Ux×V˙’>??×?˙Ux×V˙
U x × V ˙
) is proportional to the plasma concentration of x ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-9-Frame class=MathJax style="POSITION: relative" data-mathml='Pxa’>???Pxa
P x a
):

To equate the urinary excretion rate of x to its renal arterial plasma concentration, it is necessary to determine the rate at which x is removed from the plasma by the kidneys. This removal rate is the clearance ( C _x ).

If Eq. 3.3 is rearranged and the concentration of x in the renal artery plasma ( <SPAN role=presentation tabIndex=0 id=MathJax-Element-12-Frame class=MathJax style="POSITION: relative" data-mathml='Pxa’>PaxPxa
P x a
) is assumed to be identical to its concentration in a plasma sample from any peripheral blood vessel, the following relationship is obtained:

Clearance has the dimensions of volume/time, and it represents a virtual volume of plasma from which all the substance has been removed and excreted into the urine per unit time. The last point is best illustrated by considering the following example. If a substance is present in the urine at a concentration of 100 mg/mL and the urine flow rate is 1 mL/min, the excretion rate for this substance is calculated as follows:

If this substance is present in the plasma at a concentration of 1 mg/mL, its clearance according to Eq. 3.4 is as follows:

In other words, 100 mL of plasma are completely cleared of substance x each minute. The definition of clearance as a volume of plasma from which all the substance has been removed and excreted into the urine per unit time is somewhat misleading because it is not a real volume of plasma; rather, it is an virtual volume. ^a

a For most substances cleared from plasma by the kidneys, only a portion is actually removed and excreted in a single pass through the kidneys.

Glomerular Filtration Rate

The GFR of the kidney is equal to the sum of the filtration rates of all functioning nephrons. Thus it is an aggregate index of kidney function. A fall in GFR generally means that kidney disease is progressing, whereas movement toward a normal GFR generally suggests recuperation. Thus serial assessment of a patient’s GFR is essential to evaluate the severity and course of kidney disease.

One way to measure GFR is to calculate creatinine clearance. Creatinine is a by-product of normal skeletal muscle creatine metabolism, and creatinine is freely filtered across the glomerular filtration barrier into Bowman’s space. It is normally generated by the body at a fairly constant rate, and—to a first approximation—it is not appreciably reabsorbed, secreted, or metabolized by the cells of the nephron after its filtration. Accordingly the amount of creatinine excreted in the urine per minute is fairly constant at steady state (i.e., when [creatinine] is constant) and equals the amount of creatinine filtered at the glomerulus each minute ( Fig. 3.2 ):

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Structure and Function of the Kidneys Regulation of Body Fluid Osmolality: Regulation of Water Balance Physiology of Diuretic Action Regulation of Calcium and Phosphate Homeostasis Review Examination Answers to Review Examination

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