Inulin Clearance

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Glomerular Filtration and Clearance

The glomerular filtration rate (GFR) is the total volume of fluid filtered by the glomeruli per unit time. It is normally about 120 mL/min per 1.73 m2 of body surface area, equivalent to around 180 L/day. Accordingly, the volume of exchangeable extracellular fluid of the whole body (ca. 17 L) enters the renal tubules about 10 times a day. About 99% of the GFR returns to the extracellular compartment by tubular reabsorption. The mean fractional excretion of H2O is therefore about 1% of the GFR, and absolute H2O excretion (= urine output/time = Vu) is about 1 to 2 L per day. (The filtration of dissolved substances is described on p. 154).

The GFR makes up about 20% of renal plasma flow, RPF (^ p. 150). The filtration fraction (FF) is defined as the ratio of GFR/RPF. The filtration fraction is increased by atriopeptin, a peptide hormone that increases efferent arte-riolar resistance (Re) while lowering afferent arteriolar resistance (Ra). This raises the effective filtration pressure in the glomerular capillaries without significantly changing the overall resistance in the renal circulation.

The effective filtration pressure (Peff) is the driving "force" for filtration. Pef is the glomerular capillary pressure (Pcap ~ 48mmHg) minus the pressure in Bowman's capsule (PBow ~ 13 mmHg) and the oncotic pressure in plasma (ncap = 25 to 35 mmHg):

Pef at the arterial end of the capillaries equals 48-13-25 = 10 mmHg. Because of the high filtration fraction, the plasma protein concentration and, therefore, ncap values along the glomerular capillaries increase (^ p. 378) and Peff decreases. (The mean effective filtration pressure, Peff, is therefore used in Eq. 7.7.) Thus, filtration ceases (near distal end of capillary) when ncap rises to about 35 mmHg, decreasing Pef to zero (filtration equilibrium).

GFR is the product of Peff (mean for all glo-meruli), the glomerular filtration area A (dependent on the number of intact glomeruli), and the water permeability k of the glomerular filter. The ultrafiltration coefficient Kf is used to represent A • k. This yields

Indicators present in the plasma are used to measure GFR. They must have the following properties:

— They must be freely filterable

— Their filtered amount must not change due to resorption or secretion in the tubule

— They must not be metabolized in the kidney

— They must not alter renal function

Inulin, which must be infused intravenously, fulfills these requirements. Endogenous crea-tinine (normally present in blood) can also be used with certain limitations.

The amount of indicator filtered over time (^ A) is calculated as the plasma concentration of the indicator (Pm, in g/Lor mol/L) times the GFR in L/min. The same amount of indicator/time appears in the urine (conditions 2 and 3; see above) and is calculated asVu(in L/min), times the indicator conc. in u. rine (uIn, in g/L or mol/L, resp.), i.e. Pm ■ GFR = Vu ■ Um, or: VU ■ U|n

The expression on the right of Eq. 7.8 represents clearance, regardless ofwhich substance is being investigated. Therefore, the inulin or creatinine clearance represents the GFR. (Although the plasma concentration of creat-inine, Pcr, rises as the GFR falls, Pcr alone is a quite unreliable measure of GFR.)

Clearance can also be regarded as the completely indicator-free (or cleared) plasma volume flowing through the kidney per unit time. Fractional excretion (FE) is the ratio of clearance of a given substance X to inulin clearance (CX/CIn) and defines which fraction of the filtered quantity of X was excreted (cf. p. 154). FE < 1 if the substance is removed from the tubule by reabsorption (e.g. Na+, Cl-, amino acids, glucose, etc.; ^ B1), and FE > 1 if the substance is subject to filtration plus tubular secretion (^ B2). For PAH (^ p. 150), tubular secretion is so effective that FEpah ~ 5 (500%).

The absolute rate of reabsorption or secretion of a freely filterable substance X (mol/ min) is calculated as the difference between the filtered amount/time (GFR - Px) and the excreted amount/time (Vu - Ux), where a positive result means net reabsorption and a negative net secretion. (For inulin, the result would be zero.)

|— A. Inulin clearance = glomerular filtration rate (GFR)

|— A. Inulin clearance = glomerular filtration rate (GFR)

Gfr Filtration Fraction

|— B. Clearance levels (1) lower or (2) higher than inulin clearance

Glucose Amino acids Na+, Cl- etc.

Inulin Clearance

Filtration

Reabsorption

Low excretion rate

Organic anions or cations (e.g. PAH and atropine, resp.)

Filtration

Reabsorption

Low excretion rate cx cx = Fractional = fe <1 0 Cln GFR excretion '

cx = cx = Fractional = fe >10 Cln GFR excretion .

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Responses

  • Aston Hunter
    How is glomerular filtration rate calculated?
    8 years ago

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