Plasma clearance

Plasma clearance is defined as the volume of plasma from which a substance is completely cleared by the kidneys per unit time (ml/min). Calculation of the plasma clearance of certain substances can be used to determine  

In order to measure plasma clearance of a substance, the following variables must be determined  

In order to use the plasma clearance of a substance to determine GFR, the following criteria regarding the substance must be met  

A substance that fulfills these criteria is inulin, a polysaccharide found in plants. Inulin is administered intravenously to a patient at a rate that results in a constant plasma concentration over the course of at least 1 h. The urine is collected and its volume and concentration of inulin are measured. 

Because inulin is neither reabsorbed nor secreted, all of the inulin in the urine was filtered at the glomerulus. Therefore, the plasma clearance of inulin is equal to the GFR. 

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The total clearance increases in proportion to the free plasma fraction while free plasma clearance remains constant. 

Toutain PL and Bousquet-Melou A. Plasma clearance. J Vet Pharmacol Ther 2004 27 415-25. 

Note that the steady-state plasma concentration varies proportionally with the rate of infusion and inversely with the plasma clearance C/p, the definition of... 

Explain how plasma clearance of inulin is used to determine glomerular filtration rate... 

Although the measurement of GFR with inulin is quite accurate, it is inconvenient because it requires the continuous infusion of this exogenous substance for several hours. More often, in clinical situations, the plasma clearance of creatinine is used to estimate GFR. Creatinine, an end-product of muscle metabolism, is released into the blood at a fairly constant rate. Consequently, only a single blood sample and a 24-h urine collection are needed. Measurement of the plasma clearance of creatinine provides only an estimate of GFR in fact, this measurement slightly overestimates it. A small amount of creatinine is secreted into the urine (about 10% on average). In other words, the concentration of creatinine in the urine is the result of the amount filtered (as determined by GFR) plus the amount secreted. 

A substance that fulfills these criteria is para-aminohippuric acid (PAH). All of the PAH not filtered at the glomerulus is secreted by the proximal tubule. The net effect is that all of the plasma flowing through the nephrons is completely cleared of PAH. It is important to note that about 10 to 15% of the total renal plasma flow supplies regions of the kidneys that are not involved with filtration or secretion. Consequently, this plasma cannot be cleared of PAH. Therefore, the plasma clearance of PAH provides a measurement of the effective renal plasma flow, that is, the volume of plasma that actually flows through the nephrons. The ERPF is normally about 625 ml/ min. (This value is based on a renal blood flow of about 1.1 1/min and a hematocrit of about 42.)... 

The filtration fraction is the percent of the plasma flowing through the nephrons that is filtered into the tubules. It is calculated using the plasma clearance of inulin (GFR) and the plasma clearance of PAH (ERPF) ... 

Fig. 11. Plasma clearance of selected lanthanides and plutonium compared to calcium.

If the apparent plasma clearance (dose/area under the plasma concentration-time curve, equivalent to true clearance/fraction of dose absorbed) gives an implausibly high value of clearance (e.g., greater than hepatic and renal plasma flow), it is likely the bioavailability is low. However, this could be due to presystemic metabolism in addition to low absorption. 

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