When kidney disease is suspected, it is important to measure the glomerular filtration rate (GFR) since a decrease in GFR may be the first and only clinical sign. Although a 50% loss of functioning nephrons only reduces GFR by about 25%, the remaining nephrons compensate to prevent a larger decline. However, measuring GFR directly is cumbersome, so kidney function is usually assessed by measuring the plasma concentration of creatinine (PCr), which is inversely related to GFR. It should be noted that a significant decrease in GFR is required for an increase in PCr to be detected clinically. For example, a decrease in GFR from 120 to 100 mL/min is accompanied by a small increase in PCr from 1.0 to 1.2 mg/dL, representing almost a 20% decrease in GFR. In the clinical setting, estimated GFR (eGFR) takes into account various factors such as age, sex, body size, and race. A free app for calculating eGFR is available for download. The glomerular filtration barrier determines the composition of the plasma ultrafiltrate by restricting the filtration of molecules based on size and electric charge. Neutral molecules with a radius smaller than about 0.2 Å are freely filtered, while molecules larger than about 42 Å are not filtered at all. Molecules between 18 and 42 Å are filtered to varying degrees.
A fall in GFR may be the first and only clinical sign of kidney disease. Thus measuring GFR is important when kidney disease is suspected. A 50% loss of functioning nephrons reduces GFR only by about 25%. The decline in GFR is not 50% because the remaining nephrons compensate. Because measurements of GFR are cumbersome, kidney function is usually assessed in the clinical setting by measuring the plasma concentration of creatinine (PCr),which is inversely related to GFR (
Fig. 33.14 ). However, as
Fig. 33.14 shows, GFR must decline substantially before an increase in PCr can be detected in a clinical setting. For example, a fall in GFR from 120 to 100 mL/min is accompanied by an increase in PCr from 1.0 to 1.2 mg/dL. This does not appear to be a significant change in PCr, but GFR has actually fallen by almost 20%. In the clinical setting, estimated GFR (eGFR) also includes consideration of several other factors in addition to the plasma concentration of creatinine, including age, sex, body size, and race. A free app to calculate eGFR can be downloaded at: https://www.kidney.org/apps/professionals/ platelets) and is essentially protein free. The concentration • Fig. 33.14 Relationship between GFR and plasma [creatinine] (Pcr). The amount of creatinine filtered is equal to the amount excreted; thus GFR × PCr = UCr × V. Because the production of creatinine is constant, excretion must be constant to maintain creatinine balance. Therefore if GFR falls from 120 to 60 mL/min, PCr must increase from 1 to 2 mg/dL to keep filtration of creatinine and its excretion equal to the production rate.
1.0 0.8 0.6 0.4 of salts and organic molecules (e.g., glucose, amino acids) is similar in plasma and the ultrafiltrate. Starling forces drive ultrafiltration across the glomerular capillaries, and changes in these forces alter GFR. GFR and RPF are normally held within very narrow ranges by a phenomenon called autoregulation. The next sections of this chapter review the composition of the glomerular filtrate, the dynamics of its formation, and the relationship between RPF and GFR. In addition, factors that contribute to autoregulation and regulation of GFR and RBF are discussed.
Determinants of Ultrafiltrate Composition
The glomerular filtration barrier determines the composition of the plasma ultrafiltrate. It restricts filtration of molecules on the basis of both size and electric charge (
Fig. 33.15 ). In general, neutral molecules with a radius smaller than about 0.2 • Fig. 33.15 Influence of the size and electric charge of dextran on its filterability. A value of 1 indicates that it is filtered freely, whereas a value of zero indicates that it is not filtered. The filterability of dextrans between approximately 18 and 42 Å depends on charge. Dextrans larger than 42 Å are not filtered regardless of charge, and polycationic dextrans and neutral dextrans smaller than 18 Å are freely filtered. The major proteins in plasma are albumin and immunoglobulins. Because the effective molecular radii of immunoglobulin (Ig)G (53 Å) and IgM (>100 Å) are greater than 42 Å, they are not filtered. Although the effective molecular radius of albumin is 35 Å, it is a polyanionic protein, so it does not cross the filtration barrier to a significant degree.
18 Å are freely filtered, molecules larger than about 42 Å are not filtered, and molecules between about 18 and 42 Å are filtered to varying degrees.