glomerular filtration rate glomerular filtration rate renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin d. diagram showing a schematic nephron and its blood supply. the basic physiologic mechanisms of handling fluid and electrolytes by the nephron - filtration, secretion, reabsorption, and excretion - are labelled. one of the measures of kidney function is the glomerular filtration rate (gfr). glomerular filtration rate describes the flow rate of filtered fluid through the kidney. the creatinine clearance rate (ccr or crcl) is the volume of blood plasma that is cleared of creatinine per unit time and is a useful measure for approximating the gfr. creatinine clearance exceeds gfr due to creatinine secretion, which can be blocked by cimetidine. both gfr and ccr may be accurately calculated by comparative measurements of substances in the blood and urine, or estimated by formulas using just a blood test result (egfr and eccr) the results of these tests are used to assess the excretory function of the kidneys. staging of chronic kidney disease is based on categories of gfr as well as albuminuria and cause of kidney disease. the normal range of gfr, adjusted for body surface area, is 100–130 average 125 ml/min/1.73m2 in men and 90–120 ml/min/1.73m2 in women younger than the age of 40. in children, gfr measured by inulin clearance is 110 ml/min/1.73 m2 until 2 years of age in both sexes, and then it progressively decreases. after age 40, gfr decreases progressively with age, by 0.4–1.2 ml/min per year. estimated gfr (egfr) is now recommended by clinical practice guidelines and regulatory agencies for routine evaluation of gfr whereas measured gfr (mgfr) is recommended as a confirmatory test when more accurate assessment is required. definition glomerular filtration rate (gfr) is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the bowman's capsule per unit time. central to the physiologic maintenance of gfr is the differential basal tone of the afferent and efferent arterioles (see diagram). in other words, the filtration rate is dependent on the difference between the higher blood pressure created by vasoconstriction of the input or afferent arteriole versus the lower blood pressure created by lesser vasoconstriction of the output or efferent arteriole. gfr is equal to the renal clearance rate when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys. the rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood. relating this principle to the below equation – for the substance used, the product of urine concentration and urine flow equals the mass of substance excreted during the time that urine has been collected. this mass equals the mass filtered at the glomerulus as nothing is added or removed in the nephron. dividing this mass by the plasma concentration gives the volume of plasma which the mass must have originally come from, and thus the volume of plasma fluid that has entered bowman's capsule within the aforementioned period of time. the gfr is typically recorded in units of volume per time, e.g., milliliters per minute (ml/min). compare to filtration fraction. g f r = urine concentration × urine flow plasma concentration \times there are several different techniques used to calculate or estimate the glomerular filtration rate (gfr or egfr). the above formula only applies for gfr calculation when it is equal to the clearance rate. measurement creatinine in clinical practice, however, creatinine clearance or estimates of creatinine clearance based on the serum creatinine level are used to measure gfr. creatinine is produced naturally by the body (creatinine is a breakdown product of creatine phosphate, which is found in muscle). it is freely filtered by the glomerulus, but also actively secreted by the peritubular capillaries in very small amounts such that creatinine clearance overestimates actual gfr by 10% to 20%. this margin of error is acceptable, considering the ease with which creatinine clearance is measured. unlike precise gfr measurements involving constant infusions of inulin, creatinine is already at a steady-state concentration in the blood, and so measuring creatinine clearance is much less cumbersome. however, creatinine estimates of gfr have their limitations. all of the estimating equations depend on a prediction of the 24-hour creatinine excretion rate, which is a function of muscle mass which is quite variable. one of the equations, the cockcroft and gault equation (see below) does not correct for race. with a higher muscle mass, serum creatinine will be higher for any given rate of clearance. inulin the gfr can be determined by injecting inulin or the inulin-analog sinistrin into the blood stream. since both inulin and sinistrin are neither reabsorbed nor secreted by the kidney after glomerular filtration, their rate of excretion is directly proportional to the rate of filtration of water and solutes across the glomerular filter. incomplete urine collection is an important source of error in inulin clearance measurement. using inulin to measure kidney function is the "gold standard" for comparison with other means of estimating glomerular filtration rate. radioactive tracers gfr can be accurately measured using radioactive substances, in particular chromium-51 and technetium-99m. these come close to the ideal properties of inulin (undergoing only glomerular filtration) but can be measured more practically with only a few urine or blood samples. measurement of renal or plasma clearance of 51cr-edta is widely used in europe but not available in the united states, where 99mtc-dtpa may be used instead. renal and plasma clearance 51cr-edta has been shown to be accurate in comparison with the gold standard, inulin. use of 51cr‑edta is considered a reference standard measure in uk guidance. cystatin c problems with creatinine (varying muscle mass, recent meat ingestion (much less dependent on the diet than urea), etc.) have led to evaluation of alternative agents for estimation of gfr. one of these is cystatin c, a ubiquitous protein secreted by most cells in the body (it is an inhibitor of cysteine protease). cystatin c is freely filtered at the glomerulus. after filtration, cystatin c is reabsorbed and catabolized by the tubular epithelial cells, with only small amounts excreted in the urine. cystatin c levels are therefore measured not in the urine, but in the bloodstream. equations have been developed linking estimated gfr to serum cystatin c levels. most recently, some proposed equations have combined (sex, age and race) adjusted cystatin c and creatinine. the most accurate is (sex, age and race) adjusted cystatin c, followed by (sex, age and race) adjusted creatinine and then cystatine c alone in slightly different with adjusted creatinine. calculation more precisely, gfr is the fluid flow rate between the glomerular capillaries and the bowman's capsule: q = d ⁡ v d ⁡ t = k f × ( p g − p b − π g + π b ) v \over \operatorname t}=k_\times (p_-p_-\pi _+\pi _)} where: q is the gfr. k f is called the filtration constant and is defined as the product of the hydraulic conductivity and the surface area of the glomerular capillaries. p g is the hydrostatic pressure within the glomerular capillaries. p b is the hydrostatic pressure within the bowman's capsule. π g is the colloid osmotic pressure within the glomerular capillaries. and π b is the colloid osmotic pressure within the bowman's capsule. kf because this constant is a measurement of hydraulic conductivity multiplied by the capillary surface area, it is almost impossible to measure physically. however, it can be determined experimentally. methods of determining the gfr are listed in the above and below sections and it is clear from our equation that k f can be found by dividing the experimental gfr by the net filtration pressure: k f = gfr net filt. pressure = gfr ( p g − p b − π g + π b ) ==-p_-\pi _+\pi _)}}} pg the hydrostatic pressure within the glomerular capillaries is determined by the pressure difference between the fluid entering immediately from the afferent arteriole and leaving through the efferent arteriole. the pressure difference is approximated by the product of the total resistance of the respective arteriole and the flux of blood through it: p a − p g = r a × q a -p_=r_\times q_ p g − p e = r e × q e -p_=r_\times q_ where: p a is the afferent arteriole pressure. p g is the hydrostatic pressure within the glomerular capillaries. p e is the efferent arteriole pressure. r a is the afferent arteriole resistance. r e is the efferent arteriole resistance. q a is the afferent arteriole flux. and, q e is the efferent arteriole flux. pb the pressure in the bowman's capsule and proximal tubule can be determined by the difference between the pressure in the bowman's capsule and the descending tubule: p b − p d = r d × ( q a − q e ) -p_=r_\times (q_-q_)} where: p d is the pressure in the descending tubule. and, r d is the resistance of the descending tubule. πg blood plasma has a good many proteins in it and they exert an inward directed force called the osmotic pressure on the water in hypotonic solutions across a membrane, i.e., in the bowman's capsule. because plasma proteins are virtually incapable of escaping the glomerular capillaries, this oncotic pressure is defined, simply, by the ideal gas law: π g = r t c =rtc} where: r is the universal gas constant t is the temperature. and, c is concentration in mol/l of plasma proteins (remember the solutes can freely diffuse through the glomerular capsule). πb this value is almost always taken to be equal to zero because in a healthy nephron, there should be no proteins in the bowman's capsule. clearance and filtration fraction filtration fraction the filtration fraction is the amount of plasma that is actually filtered through the kidney. this can be defined using the equation: ff=gfr/rpf ff is the filtration fraction gfr is the glomerular filtration rate rpf is the renal plasma flow normal human ff is 20%. renal clearance cx=(ux)v/px cx is the clearance of x (normally in units of ml/min). ux is the urine concentration of x. px is the plasma concentration of x. v is the urine flow rate. estimation in clinical practice, however, creatinine clearance or estimates of creatinine clearance based on the serum creatinine level are used to measure gfr. creatinine is produced naturally by the body (creatinine is a breakdown product of creatine phosphate, which is found in muscle). it is freely filtered by the glomerulus, but also actively secreted by the peritubular capillaries in very small amounts such that creatinine clearance overestimates actual gfr by 10% to 20%. this margin of error is acceptable, considering the ease with which creatinine clearance is measured. unlike precise gfr measurements involving constant infusions of inulin, creatinine is already at a steady-state concentration in the blood, and so measuring creatinine clearance is much less cumbersome. however, creatinine estimates of gfr have their limitations. all of the estimating equations depend on a prediction of the 24-hour creatinine excretion rate, which is a function of muscle mass which is quite variable. one of the equations, the cockcroft and gault equation (see below) does not correct for race. with a higher muscle mass, serum creatinine will be higher for any given rate of clearance. a common mistake made when just looking at serum creatinine is the failure to account for muscle mass. hence, an older woman with a serum creatinine of 1.4 mg/dl may actually have a moderately severe chronic kidney disease, whereas a young muscular male can have a normal level of renal function at this serum creatinine level. creatinine-based equations should be used with caution in cachectic patients and patients with cirrhosis. they often have very low muscle mass and a much lower creatinine excretion rate than predicted by the equations below, such that a cirrhotic patient with a serum creatinine of 0.9 mg/dl may have a moderately severe degree of chronic kidney disease. estimated gfr (egfr) is now recommended by clinical practice guidelines and regulatory agencies for routine evaluation of gfr whereas measured gfr