Physiology 5th Ed.

RENAL CLEARANCE

Clearance is a general concept that describes the rate at which substances are removed (or cleared) from plasma. Thus, whole-body clearance means the total rate of removal of a substance by all organs, hepatic clearance means the rate of removal by the liver, and renal clearance means the rate of removal by the kidneys. The concept of renal clearance is being introduced at this point because it is employed in several basic concepts of renal physiology discussed throughout the chapter. For reference, see the tables of commonly used abbreviations (Table 6-3) and commonly used equations (Table 6-4).

Table 6–3 Commonly Used Abbreviations in Renal Physiology

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Table 6–4 Commonly Used Equations in Renal Physiology

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By definition, renal clearance is the volume of plasma completely cleared of a substance by the kidneys per unit time. The higher the renal clearance, the more plasma that is cleared of the substance. Substances with the highest renal clearances may be completely removed on a single pass of blood through the kidneys; substances with the lowest renal clearances are not removed at all.

The equation for renal clearance is as follows:

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where

C

= Clearance (mL/min)

[U]x

= Urine concentration of substance X (mg/mL)

image

= Urine flow rate per minute (mL/min)

[P]x

= Plasma concentration of substance X (mg/mL)

Thus, renal clearance is the ratio of urinary excretion ([U]x × image) to plasma concentration. For a given plasma concentration, renal clearance of a substance increases as the urinary excretion increases. Again, the units of clearance are volume per unit time (e.g., mL/min; L/hour; L/day), which means the volume of plasma cleared of the substance per unit time.

Clearance of Various Substances

Renal clearance can be calculated for any substance. Depending on the characteristics of the substance and its renal handling, renal clearance can vary from zero to greater than 600 mL/min. For example, renal clearance of albuminis approximately zero because, normally, albumin is not filtered across the glomerular capillaries. The renal clearance of glucose is also zero, although for a different reason: Glucose is filtered and then completely reabsorbed back into the bloodstream. Other substances such as Na+, urea, phosphate, and Cl have clearances that are higher than zero because they are filtered and partially reabsorbed. Inulin, a fructose polymer, is a special case. Inulin is freely filtered across the glomerular capillaries, but it is neither reabsorbed nor secreted; therefore, its clearance measures the glomerular filtration rate. Organic acids such as para-aminohippuric acid (PAH) have the highest clearances of all substances because they are both filtered and secreted.

Clearance Ratios

Inulin has unique properties that make it the only substance whose clearance is exactly equal to the glomerular filtration rate (GFR). Inulin is freely filtered across the glomerular capillaries, but once filtered, it is neither reabsorbed nor secreted. Thus, the amount of inulin filtered will be exactly equal to the amount of inulin excreted. For these reasons, inulin is a reference substance called a glomerular marker.

The clearance of any substance (x) can be compared with the clearance of inulin and is expressed as the clearance ratio. Thus,

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The meanings of various values of the clearance ratio are as follows:

image Cx/Cinulin = 1.0. The clearance of x equals the clearance of inulin. The substance also must be a glomerular marker (filtered, but neither reabsorbed nor secreted).

image Cx/Cinulin <1.0. The clearance of x is lower than the clearance of inulin. Either the substance is not filtered, or it is filtered and subsequently reabsorbed. For example, albumin is not filtered, and the clearance of albumin is less than the clearance of inulin. The clearances of Na+, Cl, HCO3, phosphate, urea, glucose, and amino acids also are less than the clearance of inulin because these substances are filtered and then reabsorbed.

image Cx/Cinulin > 1.0. The clearance of x is higher than the clearance of inulin. The substance is filtered and secreted. Examples of substances whose clearances are higher than that of inulin are organic acids and bases and, under some conditions, K+.

SAMPLE PROBLEM. In a 24-hour period, 1.44 L of urine is collected from a man receiving an infusion of inulin. In his urine, the [inulin] is 150 mg/mL and the [Na+] is 200 mEq/L. In his plasma, the [inulin] is 1 mg/mL and the [Na+] is 140 mEq/L. What is the clearance ratio for Na+, and what is the significance of its value?

SOLUTION. The clearance ratio for Na+ is the clearance of Na+ relative to the clearance of inulin. The clearance equation for any substance is C = [U] × image. All of the values needed are provided in the description, although urine flow rate (image) must be calculated.

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The calculated clearance ratio for Na+ of 0.01 (or 1%) provides a great deal of information about the renal handling of Na+. Because Na+ is freely filtered across the glomerular capillaries, it also must be extensively reabsorbed by the renal tubule, making its clearance much less than the clearance of inulin. The clearance ratio of 0.01 means that only 1% of the filtered Na+ is excreted. Stated differently, 99% of the filtered Na+ must have been reabsorbed.