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Renal functions include maintaining an acid–base balance; regulating
fluid balance Fluid balance is an aspect of the homeostasis of organisms in which the amount of water in the organism needs to be controlled, via osmoregulation and behavior, such that the concentrations of electrolytes ( salts in solution) in the various b ...
; regulating
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...
,
potassium Potassium is the chemical element with the symbol K (from Neo-Latin '' kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmos ...
, and other
electrolyte An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon ...
s; clearing
toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...
s; absorption of
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
,
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s, and other small molecules; regulation of
blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure ...
; production of various
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s, such as
erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...
; and activation of
vitamin D Vitamin D is a group of Lipophilicity, fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group ar ...
. 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. Creatinine clearance rate (CCr or CrCl) is the volume of
blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the int ...
that is cleared of
creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...
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 Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. The development of longer-acting H2 r ...
. 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 Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
is based on categories of GFR as well as
albuminuria Albuminuria is a pathological condition wherein the protein albumin is abnormally present in the urine. It is a type of proteinuria. Albumin is a major plasma protein (normally circulating in the blood); in healthy people, only trace amounts of ...
and cause of
kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
. 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 The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
(kidney) glomerular capillaries into the
Bowman's capsule Bowman's capsule (or the Bowman capsule, capsula glomeruli, or glomerular capsule) is a cup-like sac at the beginning of the tubular component of a nephron in the mammalian kidney that performs the first step in the filtration of blood to form u ...
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 Min or MIN may refer to: Places * Fujian, also called Mǐn, a province of China ** Min Kingdom (909–945), a state in Fujian * Min County, a county of Dingxi, Gansu province, China * Min River (Fujian) * Min River (Sichuan) * Mineola (Amtr ...
). Compare to filtration fraction. :GFR = \frac 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 Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...
is a breakdown product of
creatine phosphate Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated form of creatine that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine trip ...
, 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 Sinistrin is a naturally occurring sugar polymer or polysaccharide, also known as polyfructosane. It belongs to the fructan group, like inulin. As it is the case with similar substances, such as fructans or inulin, sinistrin acts as an energy stor ...
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 Naturally occurring chromium (24Cr) is composed of four stable isotopes; 50Cr, 52Cr, 53Cr, and 54Cr with 52Cr being the most abundant (83.789% natural abundance). 50Cr is suspected of decaying by β+β+ to 50Ti with a half-life of (more than) 1.8 ...
and
technetium-99m Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medica ...
. 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 Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...
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 Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin, or neuroendocrine basic polypeptide), a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicti ...
, 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: : = K_f \times (P_G - P_B - \Pi_G + \Pi_B) Where: * is the GFR. * K_f is called the ''filtration constant'' and is defined as the product of the
hydraulic conductivity Hydraulic conductivity, symbolically represented as (unit: m/s), is a property of porous materials, soils and rocks, that describes the ease with which a fluid (usually water) can move through the pore space, or fractures network. It depends on ...
and the surface area of the glomerular capillaries. * P_G is the
hydrostatic pressure Fluid statics or hydrostatics is the branch of fluid mechanics that studies the condition of the equilibrium of a floating body and submerged body " fluids at hydrostatic equilibrium and the pressure in a fluid, or exerted by a fluid, on an i ...
within the glomerular capillaries. * P_B is the hydrostatic pressure within the Bowman's capsule. * \Pi_G is the
colloid osmotic pressure Oncotic pressure, or colloid osmotic-pressure, is a form of osmotic pressure induced by the proteins, notably albumin, in a blood vessel's plasma (blood/liquid) that causes a pull on fluid back into the capillary. Participating colloids displac ...
within the glomerular capillaries. * and \Pi_B is the colloid osmotic pressure within the Bowman's capsule.


Because this constant is a measurement of
hydraulic conductivity Hydraulic conductivity, symbolically represented as (unit: m/s), is a property of porous materials, soils and rocks, that describes the ease with which a fluid (usually water) can move through the pore space, or fractures network. It depends on ...
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 = \frac=\frac


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 \times Q_a : P_G - P_e = R_e \times Q_e Where: * P_a is the afferent arteriole pressure. * P_G is the
hydrostatic pressure Fluid statics or hydrostatics is the branch of fluid mechanics that studies the condition of the equilibrium of a floating body and submerged body " fluids at hydrostatic equilibrium and the pressure in a fluid, or exerted by a fluid, on an i ...
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.


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 \times (Q_a - Q_e) Where: * P_d is the pressure in the descending tubule. * And, R_d is the resistance of the descending tubule.


Blood plasma has a good many proteins in it and they exert an inward directed force called the
osmotic pressure Osmotic pressure is the minimum pressure which needs to be applied to a solution to prevent the inward flow of its pure solvent across a semipermeable membrane. It is also defined as the measure of the tendency of a solution to take in a pure ...
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: : \Pi_G = RTc Where: * R is the
universal gas constant The molar gas constant (also known as the gas constant, universal gas constant, or ideal gas constant) is denoted by the symbol or . It is the molar equivalent to the Boltzmann constant, expressed in units of energy per temperature increment per ...
* T is the temperature. * And, c is concentration in mol/L of plasma ''proteins'' (remember the solutes can freely diffuse through the glomerular capsule).


This value is almost always taken to be equal to zero because in a healthy
nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...
, 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 is the filtration fraction * GFR is the glomerular filtration rate * RPF is the renal plasma flow Normal human FF is 20%.


Renal clearance

* is the clearance of X (normally in units of mL/min). * is the urine concentration of X. * is the plasma concentration of X. * 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 Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...
is a breakdown product of
creatine phosphate Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated form of creatine that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine trip ...
, 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 Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
, 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 Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
. 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 (mGFR) is recommended as a confirmatory test when more accurate assessment is required.


Creatinine clearance CCr

One method of determining GFR from creatinine is to collect urine (usually for 24 h) to determine the amount of creatinine that was removed from the blood over a given time interval. If one removes 1440 mg in 24 h, this is equivalent to removing 1 mg/min. If the blood concentration is 0.01 mg/mL (1 mg/dL), then one can say that 100 mL/min of blood is being "cleared" of creatinine, since, to get 1 mg of creatinine, 100 mL of blood containing 0.01 mg/mL would need to have been cleared. Creatinine clearance (CCr) is calculated from the creatinine concentration in the collected urine sample (UCr),
urine flow rate Urine flow rate or urinary flow rate is the volumetric flow rate of urine during urination. It is a measure of the quantity of urine excreted in a specified period of time (per second or per minute). It is measured with uroflowmetry, a type of flow ...
(V''dt''), and the plasma concentration (PCr). Since the product of urine concentration and urine flow rate yields creatinine excretion rate, which is the rate of removal from the blood, creatinine clearance is calculated as removal rate per min (UCr×V''dt'') divided by the plasma creatinine concentration. This is commonly represented mathematically as :C_ = \frac Example: A person has a plasma creatinine concentration of 0.01 mg/mL and in 1 hour produces 60 mL of urine with a creatinine concentration of 1.25 mg/mL. :C_ = \frac \mathrm\mathrm = \frac \mathrm\mathrm = \frac \mathrm\mathrm = \mathrm The common procedure involves undertaking a 24-hour urine collection, from empty-bladder one morning to the contents of the bladder the following morning, with a comparative blood test then taken. The urinary flow rate is still calculated per minute, hence: :C_ = \frac \mathrm To allow comparison of results between people of different sizes, the CCr is often corrected for the body surface area (BSA) and expressed compared to the average sized man as mL/min/1.73 m2. While most adults have a BSA that approaches 1.7 m2 (1.6 m2 to 1.9 m2), extremely obese or slim patients should have their CCr corrected for their ''actual'' BSA. :C_\text = \frac \mathrm :BSA can be calculated on the basis of weight and height. Twenty-four-hour urine collection to assess creatinine clearance is no longer widely performed, due to difficulty in assuring complete specimen collection. To assess the adequacy of a complete collection, one always calculates the amount of creatinine excreted over a 24-hour period. This amount varies with muscle mass and is higher in young people/old, and in men/women. An unexpectedly low or high 24-hour creatinine excretion rate voids the test. Nevertheless, in cases where estimates of creatinine clearance from serum creatinine are unreliable, creatinine clearance remains a useful test. These cases include "estimation of GFR in individuals with variation in dietary intake (vegetarian diet, creatine supplements) or muscle mass (amputation, malnutrition, muscle wasting), since these factors are not specifically taken into account in prediction equations." A number of formulae have been devised to estimate GFR or Ccr values on the basis of serum creatinine levels. Where not otherwise stated serum creatinine is assumed to be stated in mg/dL, not μmol/L—divide by 88.4 to convert from μmol/Lto mg/dL.


Cockcroft-Gault formula

A commonly used surrogate marker for the estimation of creatinine clearance is the Cockcroft-Gault (CG) formula, which in turn estimates GFR in ml/min: It is named after the scientists, the asthmologist (b. 1946) and the nephrologist (1925–2003), who first published the formula in 1976, and it employs serum
creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...
measurements and a patient's weight to predict the creatinine clearance. The formula, as originally published, is: :eC_ = \frac :This formula expects weight to be measured in
kilogram The kilogram (also kilogramme) is the unit of mass in the International System of Units (SI), having the unit symbol kg. It is a widely used measure in science, engineering and commerce worldwide, and is often simply called a kilo colloquially. ...
s and creatinine to be measured in mg/dL, as is standard in the USA. The resulting value is multiplied by a constant of 0.85 if the patient is female. This formula is useful because the calculations are simple and can often be performed without the aid of a
calculator An electronic calculator is typically a portable electronic device used to perform calculations, ranging from basic arithmetic to complex mathematics. The first solid-state electronic calculator was created in the early 1960s. Pocket-sized ...
. When serum creatinine is measured in μmol/L: :eC_ = \frac :Where ''Constant'' is for men and for women. One interesting feature of the Cockcroft and Gault equation is that it shows how dependent the estimation of CCr is based on age. The age term is (140 – age). This means that a 20-year-old person (140 – 20 = 120) will have twice the creatinine clearance as an 80-year-old (140 – 80 = 60) for the same level of serum creatinine. The C-G equation assumes that a woman will have a 15% lower creatinine clearance than a man at the same level of serum creatinine.


Modification of Diet in Renal Disease (MDRD) formula

Another formula for calculating the GFR is the one developed by the ''Modification of Diet in Renal Disease Study Group''. Most laboratories in Australia, and the United Kingdom now calculate and report the estimated GFR along with creatinine measurements and this forms the basis of diagnosis of
chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
. The adoption of the automatic reporting of MDRD-eGFR has been widely criticised. The most commonly used formula is the "4-variable MDRD", which estimates GFR using four variables: serum creatinine, age, ethnicity, and gender. The original MDRD used six variables with the additional variables being the
blood urea nitrogen Blood urea nitrogen (BUN) is a medical test that measures the amount of urea nitrogen found in blood. The liver produces urea in the urea cycle as a waste product of the digestion of protein. Normal human adult blood should contain 6 to 20 mg/dL ...
and
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...
levels. The equations have been validated in patients with chronic kidney disease; however, both versions underestimate the GFR in healthy patients with GFRs over 60 mL/min. The equations have not been validated in acute renal failure. For creatinine in μmol/L: :\text = \text\ \times \
text Text may refer to: Written word * Text (literary theory), any object that can be read, including: **Religious text, a writing that a religious tradition considers to be sacred **Text, a verse or passage from scripture used in expository preachin ...
\ \times \ \text^ \ \times \text \ \times \text For creatinine in mg/dL: :\text = \text\ \times \
text Text may refer to: Written word * Text (literary theory), any object that can be read, including: **Religious text, a writing that a religious tradition considers to be sacred **Text, a verse or passage from scripture used in expository preachin ...
\ \times \ \text^ \ \times \text \ \times \text :Creatinine levels in μmol/L can be converted to mg/dL by dividing them by 88.4. The 32788 number above is equal to 186×88.41.154. A more elaborate version of the MDRD equation also includes serum albumin and
blood urea nitrogen Blood urea nitrogen (BUN) is a medical test that measures the amount of urea nitrogen found in blood. The liver produces urea in the urea cycle as a waste product of the digestion of protein. Normal human adult blood should contain 6 to 20 mg/dL ...
(BUN) levels: :\text = \text\ \times \
text Text may refer to: Written word * Text (literary theory), any object that can be read, including: **Religious text, a writing that a religious tradition considers to be sacred **Text, a verse or passage from scripture used in expository preachin ...
\ \times \ \text^ \ \times \text \ \times \text \ \times \ \text^ \ \times \ \text^ :where the creatinine and blood urea nitrogen concentrations are both in mg/dL. The albumin concentration is in g/dL. These MDRD equations are to be used only if the laboratory has NOT calibrated its serum creatinine measurements to isotope dilution mass spectrometry (IDMS). When IDMS-calibrated serum creatinine is used (which is about 6% lower), the above equations should be multiplied by 175/186 or by 0.94086. Since these formulae do not adjust for body size, results are given in units of mL/min per 1.73 m2, 1.73 m2 being the estimated body surface area of an adult with a mass of 63 kg and a height of 1.7m.


CKD-EPI formula

The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was published in May 2009. It was developed in an effort to create a formula more accurate than the MDRD formula, especially when actual GFR is greater than 60 mL/min per 1.73 m2. This is the formula currently recommended by NICE in the UK. Researchers pooled data from multiple studies to develop and validate this new equation. They used 10 studies that included 8254 participants, randomly using 2/3 of the data sets for development and the other 1/3 for internal validation. Sixteen additional studies, which included 3896 participants, were used for external validation. The CKD-EPI equation performed better than the MDRD (Modification of Diet in Renal Disease Study) equation, especially at higher GFR, with less bias and greater accuracy. When looking at NHANES (National Health and Nutrition Examination Survey) data, the median estimated GFR was 94.5 mL/min per 1.73 m2 vs. 85.0 mL/min per 1.73 m2, and the prevalence of chronic kidney disease was 11.5% versus 13.1%. Despite its overall superiority to the MDRD equation, the CKD-EPI equations performed poorly in certain populations, including black women, the elderly and the obese, and was less popular among clinicians than the MDRD estimate. The CKD-EPI equation is: :\mathrm = 141\ \times \ \mathrm^ \ \times \ \mathrm^ \ \times \ 0.993^\text \ \times \text \ \times \text \ where SCr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, a is −0.329 for females and −0.411 for males, min indicates the minimum of SCr/k or 1, and max indicates the maximum of SCr/k or 1. As separate equations for different populations: For creatinine (IDMS calibrated) in mg/dL: ;Male, not black : If serum creatinine (Scr) ≤ 0.9 :: \mathrm = 141\ \times \ \mathrm^ \ \times \ 0.993^\text \ : If serum creatinine (Scr) > 0.9 :: \mathrm = 141\ \times \ \mathrm^ \ \times \ 0.993^\text \ ;Female, not black : If serum creatinine (Scr) ≤ 0.7 :: \mathrm = 144\ \times \ \mathrm^ \ \times \ 0.993^\text \ : If serum creatinine (Scr) > 0.7 :: \mathrm = 144\ \times \ \mathrm^ \ \times \ 0.993^\text \ ;Black male : If serum creatinine (Scr) ≤ 0.9 :: \mathrm = 163\ \times \ \mathrm^ \ \times \ 0.993^\text \ : If serum creatinine (Scr) > 0.9 :: \mathrm = 163\ \times \ \mathrm^ \ \times \ 0.993^\text \ ;Black female : If serum creatinine (Scr) ≤ 0.7 :: \mathrm = 166\ \times \ \mathrm^ \ \times \ 0.993^\text \ : If serum creatinine (Scr) > 0.7 :: \mathrm = 166\ \times \ \mathrm^ \ \times \ 0.993^\text \ This formula was developed by Levey et al. The formula CKD-EPI may provide improved cardiovascular risk prediction over the MDRD Study formula in a middle-age population.


Mayo Quadratic formula

Another estimation tool to calculate GFR is the Mayo Quadratic formula. This formula was developed by Rule et al., in an attempt to better estimate GFR in patients with preserved kidney function. It is well recognized that the MDRD formula tends to underestimate GFR in patients with preserved kidney function. Studies in 2008 found that the Mayo Clinic Quadratic Equation compared moderately well with radionuclide GFR, but had inferior bias and accuracy than the MDRD equation in a clinical setting. The equation is: :\text = \text If Serum Creatinine < 0.8 mg/dL, use 0.8 mg/dL for Serum Creatinine.


Schwartz formula

In children, the Schwartz formula is used. This employs the serum
creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...
(mg/dL), the child's height (cm) and a constant to estimate the glomerular filtration rate: :\text = \frac\text :Where ''k'' is a constant that depends on muscle mass, which itself varies with a child's age: ::In first year of life, for pre-term babies ''k''=0.33 and for full-term infants ''k''=0.45 ::For infants and children of age 1 to 12 years, ''k''=0.55. The method of selection of the constant ''k'' has been questioned as being dependent upon the gold-standard of renal function used (i.e. inulin clearance, creatinine clearance, etc.) and also may be dependent upon the urinary flow rate at the time of measurement. In 2009 the formula was updated to use standardized serum creatinine (recommend ''k''=0.413) and additional formulas that allow improved precision were derived if serum ''cystatin C'' is measured in addition to serum creatinine.


IDMS standardization effort

One problem with any creatinine-based equation for GFR is that the methods used to assay creatinine in the blood differ widely in their susceptibility to non-specific chromogens, which cause the creatinine value to be overestimated. In particular, the MDRD equation was derived using serum creatinine measurements that had this problem. The NKDEP program in the United States has attempted to solve this problem by trying to get all laboratories to calibrate their measures of creatinine to a "gold standard", which in this case is isotope dilution mass spectrometry (IDMS). In late 2009 not all labs in the U.S. had changed over to the new system. There are two forms of the MDRD equation that are available, depending on whether or not creatinine was measured by an IDMS-calibrated assay. The CKD-EPI equation is designed to be used with IDMS-calibrated serum creatinine values only.


Normal ranges

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.


Decreased GFR

A decreased renal function can be caused by many types of
kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
. Upon presentation of decreased renal function, it is recommended to perform a
history History (derived ) is the systematic study and the documentation of the human activity. The time period of event before the invention of writing systems is considered prehistory. "History" is an umbrella term comprising past events as well ...
and
physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the pati ...
, as well as performing a
renal ultrasound Renal ultrasonography (Renal US) is the examination of one or both kidneys using medical ultrasound. Ultrasonography of the kidneys is essential in the diagnosis and management of kidney-related diseases. The kidneys are easily examined, and most ...
and a
urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and microscopic examination. Macroscopic e ...
. The most relevant items in the history are
medications A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and re ...
,
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
,
nocturia Nocturia is defined by the International Continence Society (ICS) as “the complaint that the individual has to wake at night one or more times for voiding (''i.e. to urinate'').” The term is derived from Latin ''nox, night'', and Greek '' �α ...
, gross
hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
,
family history Genealogy () is the study of families, family history, and the tracing of their lineages. Genealogists use oral interviews, historical records, genetic analysis, and other records to obtain information about a family and to demonstrate kin ...
of kidney disease,
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
and
polyuria Polyuria () is excessive or an abnormally large production or passage of urine (greater than 2.5 L or 3 L over 24 hours in adults). Increased production and passage of urine may also be termed diuresis. Polyuria often appears in conjunction wi ...
. The most important items in a physical examination are signs of
vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...
,
lupus erythematosus Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...
,
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
,
endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
and
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...
. A urinalysis is helpful even when not showing any pathology, as this finding suggests an extrarenal etiology.
Proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
and/or
urinary sediment Urinary casts are microscopic cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, wher ...
usually indicates the presence of
glomerular disease ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...
.
Hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
may be caused by glomerular disease or by a disease along the
urinary tract The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, c ...
. The most relevant assessments in a
renal ultrasound Renal ultrasonography (Renal US) is the examination of one or both kidneys using medical ultrasound. Ultrasonography of the kidneys is essential in the diagnosis and management of kidney-related diseases. The kidneys are easily examined, and most ...
are renal sizes, echogenicity and any signs of
hydronephrosis Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of t ...
. Renal enlargement usually indicates diabetic nephropathy, focal segmental glomerular sclerosis or myeloma. Renal atrophy suggests longstanding chronic renal disease.


Chronic kidney disease stages

Risk factors for kidney disease include diabetes, high blood pressure, family history, older age, ethnic group and smoking. For most patients, a GFR over 60 mL/min/1.73m2 is adequate. But significant decline of the GFR from a previous test result can be an early indicator of kidney disease requiring medical intervention. The sooner kidney dysfunction is diagnosed and treated the greater odds of preserving remaining nephrons, and preventing the need for dialysis. The severity of chronic kidney disease (CKD) is described by six stages; the most severe three are defined by the MDRD-eGFR value, and first three also depend on whether there is other evidence of kidney disease (e.g.,
proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
): :0) Normal kidney function – GFR above 90 mL/min/1.73 m2 and no
proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
:1) CKD1 – GFR above 90 mL/min/1.73 m2 with evidence of kidney damage :2) CKD2 (mild) – GFR of 60 to 89 mL/min/1.73 m2 with evidence of kidney damage :3) CKD3 (moderate) – GFR of 30 to 59 mL/min/1.73 m2 :4) CKD4 (severe) – GFR of 15 to 29 mL/min/1.73 m2 :5) CKD5 kidney failure – GFR less than 15 mL/min/1.73 m2 Some people add CKD5D for those stage 5 patients requiring dialysis; many patients in CKD5 are not yet on dialysis. Note: others add a "T" to patients who have had a transplant regardless of stage. Not all clinicians agree with the above classification, suggesting that it may mislabel patients with mildly reduced kidney function, especially the elderly, as having a disease. A conference was held in 2009 regarding these controversies by Kidney Disease: Improving Global Outcomes (KDIGO) on CKD: Definition, Classification and Prognosis, gathering data on CKD prognosis to refine the definition and staging of CKD.


See also

* Clearance * Dialysis * Filtration fraction * Kt/V *
Pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
*
Renal clearance ratio The renal clearance ratio or fractional excretion is a relative measure of the speed at which a constituent of urine passes through the kidneys. It is defined by following equation: : clearance\ ratio\ of\ X = \frac * X is the analyte substance * ...
*
Renal failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
* Standardized Kt/V * Tubuloglomerular feedback * Urea reduction ratio


References


External links


Online calculators


Online GFR Calculator


for estimating pediatric renal function
Creatinine clearance calculator
(Cockcroft-Gault Equation)- by MDCalc
MDRD GFR Equation

GFR calculator using Cystatin C


Reference links



Includes professional references and GFR calculators * eGFR a
Lab Tests Online
{{DEFAULTSORT:Renal Function Renal physiology Blood tests