(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 (vdt), 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×vdt) divided by the plasma creatinine concentration. this is commonly represented mathematically as c c r = u c r × v ˙ p c r =\times 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 c r = 1.25 m g / m l × 60 m l 60 m i n 0.01 m g / m l = 1.25 m g / m l × 1 m l / m i n 0.01 m g / m l = 1.25 m g / m i n 0.01 m g / m l = 125 m l / m i n = } }}=\times } }}= } }}=\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 c r = u c r × 24-hour volume p c r × 24 × 60 m i n =\ \times \ \ \times \ 24\times 60min} }}} 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 cr-corrected = c c r × b s a 1.73 =\ \times \ }}} 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 donald william cockcroft (b. 1946) and the nephrologist matthew henry gault (1925–2003), who first published the formula in 1976, and it employs serum creatinine measurements and a patient's weight to predict the creatinine clearance. the formula, as originally published, is: e c c r = ( 140 − a g e ) × mass (in kilograms) × [ 0.85 if female ] 72 × [ serum creatinine (in mg/dl) ] = \ \times \ \ \times \ } \ \times \ }}} this formula expects weight to be measured in kilograms 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. when serum creatinine is measured in μmol/l: e c c r = ( 140 − a g e ) × mass (in kilograms) × constant [ serum creatinine (in μ m o l / l ) ] = \ \times \ \ \times \ where constant is 1.23 for men and 1.04 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. 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 and albumin 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: egfr = 32788 × [ serum creatinine ] − 1.154 × age − 0.203 × × =\ \times \ ^\ \times \ ^\ \times \ \times for creatinine in mg/dl: egfr = 186 × [ serum creatinine ] − 1.154 × age − 0.203 × × =\ \times \ ^\ \times \ ^\ \times \ \times 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 (bun) levels: egfr = 170 × [ serum creatinine ] − 0.999 × age − 0.176 × × × bun − 0.170 × albumin + 0.318 =\ \times \ ^\ \times \ ^\ \times \ \times \ \times \ ^\ \times \ ^ 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: e g f r = 141 × min ( s c r / k , 1 ) a × max ( s c r / k , 1 ) − 1.209 × 0.993 age × × =141\ \times \ \mathrm ^\ \times \ \mathrm ^\ \times \ 0.993^\ \times \ \times \ } 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 e g f r = 141 × ( s c r / 0.9 ) − 0.411 × 0.993 age =141\ \times \ \mathrm ^\ \times \ 0.993^\ } if serum creatinine (scr) > 0.9 e g f r = 141 × ( s c r / 0.9 ) − 1.209 × 0.993 age =141\ \times \ \mathrm ^\ \times \ 0.993^\ } female, not black if serum creatinine (scr) ≤ 0.7 e g f r = 144 × ( s c r / 0.7 ) − 0.329 × 0.993 age =144\ \times \ \mathrm ^\ \times \ 0.993^\ } if serum creatinine (scr) > 0.7 e g f r = 144 × ( s c r / 0.7 ) − 1.209 × 0.993 age =144\ \times \ \mathrm ^\ \times \ 0.993^\ } black male if serum creatinine (scr) ≤ 0.9 e g f r = 163 × ( s c r / 0.9 ) − 0.411 × 0.993 age =163\ \times \ \mathrm ^\ \times \ 0.993^\ } if serum creatinine (scr) > 0.9 e g f r = 163 × ( s c r / 0.9 ) − 1.209 × 0.993 age =163\ \times \ \mathrm ^\ \times \ 0.993^\ } black female if serum creatinine (scr) ≤ 0.7 e g f r = 166 × ( s c r / 0.7 ) − 0.329 × 0.993 age =166\ \times \ \mathrm ^\ \times \ 0.993^\ } if serum creatinine (scr) > 0.7 e g f r = 166 × ( s c r / 0.7 ) − 1.209 × 0.993 age =166\ \times \ \mathrm ^\ \times \ 0.993^\ } 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: egfr = exp ( 1.911 + 5.249 / [ serum creatinine ] − 2.114 / [ serum creatinine ] 2 − 0.00686 × age − ) =-0.00686\ \times \ -)}} if