Renal Clearance

Renal clearance is a measurement that allows one to analyze the activity of the kidney. It is a very peculiar measurement and this leads to confusion for students. The definition for clearance is the volume of plasma from which a substance is completely removed by the kidney in a given amount of time (usually a minute). For example, the clearance for urea is 65 ml/min. This means that the kidney removes all of the urea in 65 ml of plasma in one minute. Now, what is the actual meaning of this number? Is this high? Is it low? What significance does this number have for you? (At the moment, none at all!!)

Before talking about clearance, lets examine the flow of plasma in the kidney. Every minute approximately 625 ml of plasma goes to the kidney. This is the renal plasma flow. Some of the fluid leaves the kidney in the plasma while some leaves the kidney as urine. There are only two ways for a substance to end up in the urine: either it is filtered at the glomerulus and then not reabsorbed from the tubules, or the substance is not filtered but is secreted by from the peritubular capillaries into the tubules. In either instance, the substance ends up in the collecting duct and is excreted into the urine.

Of the 625 ml/min of plasma that goes to the glomerulus, 125 ml/min are filtered into Bowman's Capsule forming the filtrate (this is known as the glomerular filtration rate). The remaining 500 ml/min remain in the blood and enter into the peritubular capillaries. Of the 125 ml/min filtered, almost all of the water in this fluid is reabsorbed and put back into the blood. It is important to remember that the composition of the filtrate in Bowman's Capsule is identical to the composition of the plasma except that the filtrate has no (or very few) proteins (do not forget that this is not true for the urine). This means, for example, that the concentration of glucose in the filtrate in Bowman's Capsule is the same as that in the plasma. The same is true for almost all of the other solutes in the filtrate don't forget this!

Now, imagine that is a substance, lets call it P, that is freely filtered by the glomerulus and is neither reabsorbed or secreted. Therefore, all the P that is filtered will end up in the urine, no more (as P is not secreted), no less (as P is not reabsorbed). Thus all the plasma that gets filtered is cleared of P (that is, all the P in the filtrate gets excreted) while none of the P that that is not filtered (and thus remains in the plasma) is excreted. Since clearance is defined as the volume of plasma 'cleared' of a substance in 1 min, the clearance for P is 125 ml/min. This means that of the 625 ml of plasma that come to the kidney in one minute, 125 ml (the fraction that is filtered) has all of the P removed from it in that minute, the other 500 ml (the fraction that is not filtered) keeps its P as there is no way for the P get into the urine as it is not secreted. P is an imaginary substance, however, there is a real substance that has the same properties. This compound is inulin (NOTE: this is not insulin, there is no 's'). You probably have never heard of inulin as it is not normally found in the body! So, why mention inulin? Well, remember that all of the plasma that is filtered and only the plasma filtered is cleared of inulin (just like P) so that if one were to measure the clearance of inulin, it would equal the amount of plasma filtered in a minute, the glomerular filtration rate. Therefore, the clearance of inulin is equal to the glomerular filtration rate, the volume of plasma filtered in one minute. Clinicians and medical doctors will measure the clearance of inulin to determine whether the kidneys of their patients are filtering properly.

You may be wondering if the clearance of all substances are equal to the clearance of inulin. The answer is no - lets take an example. Glucose, like inulin, is freely filtered. Thus glucose is present in Bowman's Capsule. However, we know (or should know) that no glucose appears in the urine because glucose is completely reabsorbed as it passes through the tubules. Remember, inulin was not reabsorbed. This means all of the glucose that comes to the kidney is saved and leaves the kidney in the plasma and that no glucose is excreted into the urine. The clearance of glucose is therefore 0 ml/min as no plasma has its glucose removed as it passes through the kidney. This would be true for any substance that is completely reabsorbed. If I told you that the clearance of alanine (an amino acid) is 0 ml/min, you could now infer that alanine must be completely reabsorbed (as long as it is freely filtered).

Lets take a look at another substance, para amino hippuric acid (PAH), one of my favorites! PAH is freely filtered, not reabsorbed and is completely secreted by the kidney. Thus all of the PAH entering the kidney ends up in the urine, both the PAH that is filtered and that that is not filtered. This means that all the plasma entering the kidneys would be cleared of PAH. since the renal plasma flow is about 625 ml/min in a 'normal' kidney, the clearance of PAH must be 625 ml/min. Therefore, the PAH clearance is equal to the renal plasma flow. Clinicians and medical doctors measure PAH clearance to determine whether the kidneys have an adequate plasma flow.

The following table shows the clearance values for inulin, glucose and PAH as well as what the kidney 'does' with each substance.

Normal Clearance Values (ml/min)
Glucose 0 completely rebsorbed
Inulin 125 not reabsorbed and not secreted
PAH 625 completely secreted

Now, suppose you measured the clearance of a substance to be 625 ml/min. This would suggest that the kidney completely secretes this substance (that is, the kidney 'treats' this substance the same as PAH which we know is completely secreted). Using similar logic, a clearance value of 125 would suggest that the kidney neither reabsorbs nor secretes the substance and a clearance value of 0 suggests that the kidney completely reabsorbs the substance (we are assuming that the substance is freely filterable in the glomerulus).

Now, let's go back to our original example - the clearance of urea. The urea clearance has been measured to be 65 ml/min. What does the kidney 'do' with urea (does it reabsorb, secrete or neither)? Well if urea was completely reabsorbed, its clearance would be like that of glucose (0 ml/min) so urea is not completely reabsorbed. However, if urea is not reabsorbed at all (and not secreted), its clearance would be 125 ml/min - thus it must be reabsorbed just not completely. In fact, urea is partially reabsorbed. Note that the common belief concerning kidney function is that it removes urea from the blood yet the nephron paritlly reabsorbs urea!

Now, what if you measured the clearance of a substance to be 400 m/min? What do you think the kidney would 'be doing' with this substance?

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