# Creatinine Clearance Calculator

## Estimate glomerular filtration rate (GFR)

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Weight
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Creatinine

### Renal Stability

 Stable Unstable creatinine Most recent creatinine mg/dL µmol/L Less recent creatinine mg/dL µmol/L Time between creatinine values

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### About This Calculator

#### Cockcroft-Gault 19761

Particularly for renally dosing medications, the Cockcroft-Gault equation has been the long-standing gold standard for the estimation of creatinine clearance for decades. The original study was based on data from 249 male patients with stable renal function. The study used actual body weight, but mentioned that a correction factor of some kind should be used in patients with marked obesity or ascites.

$$\\ CrCl =\frac{(140-Age)*(WeightInKg)}{72*SCr} *0.85\;(if\;female)$$

#### CKD-EPI2

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed as a follow-up to the MDRD equation in an attempt to be as accurate in describing renal function at lower GFR (less than 60 mL/min/1.73 m2), but more accurate at a higher GFR. The CKD-EPI equation was developed and validated retrospectively in 8,254 patients from 10 studies. The study included all patients age > 20 years old who were not pregnant and did not have renal failure (defined as an eGFR < 15 mL/min/1.73 m2). The data set included 45% women and 87% non-black patients.

$$\\ GFR\;(mL/min/1.73 m^2) =\\ Black\;females,\;SCr\;\le\;0.7\;mg/dL:\\ 166 * (SCr/0.7)^{-0.329} * (0.993)^{Age}\\ Black\;females,\;SCr\;>\;0.7\;mg/dL:\\ 166 * (SCr/0.7)^{-1.209} * (0.993)^{Age}\\ Black\;males,\;SCr\;\le\;0.9\;mg/dL:\\ 163 * (SCr/0.9)^{-0.411} * (0.993)^{Age}\\ Black\;males,\;SCr\;>\;0.9\;mg/dL:\\ 163 * (SCr/0.9)^{-1.209} * (0.993)^{Age}\\ Non-black\;females,\;SCr\;\le\;0.7\;mg/dL:\\ 144 * (SCr/0.7)^{-0.329} * (0.993)^{Age}\\ Non-black\;females,\;SCr\;>\;0.7\;mg/dL:\\ 144 * (SCr/0.7)^{-1.209} * (0.993)^{Age}\\ Non-black\;males,\;SCr\;\le\;0.9\;mg/dL:\\ 141 * (SCr/0.9)^{-0.411} * (0.993)^{Age}\\ Non-black\;males,\;SCr\;>\;0.9\;mg/dL:\\ 141 * (SCr/0.9)^{-1.209} * (0.993)^{Age}$$

#### Jelliffe 1973 (stable renal function)3

DEPRECATED

Published as a "Letter to the Editor", the Jelliffe equation does not require a patient's height or weight because it describes renal function normalized to a body surface area of 1.73 m2. While this was a landmark equation for its era, its use has become deprecated in favor of newer equations.

$$\\ CrCl\;(mL/min*1.73\;m^2) = \frac{98 - 16*(\frac{Age-20}{20})}{SCr}\\ (CrCl\;is\;multiplied\;by\;0.9\;for\;female\;patients)$$

#### Salazar-Corcoran 19884

DEPRECATED

This equation was specifically designed to measure creatinine clearance in obese patients (defined as a BMI ≥ 30 m2). The equation is derived from a "fat free mass" equation and was shown to be superior to the Cockcroft-Gault and Jelliffe methods when using total body weight. Although interesting for historical reasons, the Salazar-Corcoran method has largely become deprecated in favor of the Cockcroft-Gault method with a body weight adjustment, such as the 40% adjustment factor equation.

$$\\ CrCl\;(for\;men)\;=\\ \frac{(137-Age)*((0.285*WeightInKg) + (12.1*HeightInMeters^2) )}{51*SCr}\\ CrCl\;(for\;women)\;=\\ \frac{(146-Age)*((0.287*WeightInKg) + (9.74*HeightInMeters^2) )}{60*SCr}$$

#### MDRD (four-variable)5,6

DEPRECATED

The MDRD equation was originally developed in 19997 as a six-variable equation, but has since been updated to a simpler, four-variable equation in two variations (to reflect the conventional and IDMS laboratory methods). The MDRD equation is more accurate than the Cockcroft-Gault method (particularly when using total body weight), but it is rarely used for drug dosing because most medications are validated using the Cockcroft-Gault method.

The MDRD equation was only studied in patients with renal dysfunction (GFR < 60 mL/min/1.73 m2), and therefore it should not be used in patients with normal renal function. For this reason, the MDRD equation has become deprecated in favor of the CKD-EPI equation, which was developed similarly to the MDRD equation, but is able to accurately describe GFR in patients without renal dysfunction.

$$\\ For\;IDMS-calibrated\;assays:\\ GFR\;(mL/min/1.73\;m^2) = 175 * (SCr)^{-1.154} * (Age)^{-0.203} \\ * (0.742\;if\;female) \\ * (1.210\;if\;African-American)\\ For\;non-IDMS\;assays:\\ GFR\;(mL/min/1.73\;m^2) = 186 * (SCr)^{-1.154} * (Age)^{-0.203} \\ * (0.742\;if\;female) \\ * (1.210\;if\;African-American)$$

#### Equations for estimating unstable renal function

Most conventional, commonly used equations to estimate renal function require that patients have a stable renal function. Usually, this is defined as having two consecutive serum creatinine values, drawn at least 24 hours apart, within 20% of each other. Unfortunately, many hospitalized patients do not have stable renal function. For this reason, other equations have been developed to aid clinicians in estimating renal function for the purposes of drug dosing.

The two most common equations for estimating unstable renal function are the Jelliffe 19728 and Chiou 19759 methods.10 All of these equations lack the robust evidence of the equations for stable renal function and are poorly validated in a large group of patients. Generally speaking, these equations are developed using a one-compartment pharmacokinetic estimation model, and are less accurate when renal function is improving (rather than worsening).11 Although the data are not compelling, these are the best equations available for this patient population.

$$\\ (Men)\;E^{SS} = IdealBW * (29.3 - (0.203*Age))\\ (Women)\;E^{SS} = IdealBW * (25.1 - (0.175*Age))\\ SCr_{avg} = (SCr1+SCr2)/2\\ E^{SS}_{corr} = E^{SS} * (1.035 - (0.0337*SCr_{avg}))\\ E = E^{SS}_{corr} - \frac{4*IdealBW*(SCr_2 - SCr_1)}{\Delta Time\;(days)}\\ CrCl (mL/min/1.73 m^2) = \frac{E}{14.4*SCr_{avg}}$$

#### Creatinine Clearance (CrCl) versus Glomerular Filtration Rate (GFR)

Creatinine clearance (CrCl) is an estimate of Glomerular Filtration Rate (GFR); however, CrCl is slightly higher than true GFR because creatinine is secreted by the proximal tubule (in addition to being filtered by the glomerulus). The additional proximal tubule secretion falsely elevates the CrCl estimate of GFR.12

Equations that express GFR (such as MDRD and CKD-EPI) express GFR in mL/min/1.73 m2. For the purposes of drug dosing or estimating GFR in patients with body size that is very different than average, GFR can be non-normalized using the following equation:12

$$\\ BSA = \sqrt{\frac{(HeightInCm * WeightInKg)}{3600}} \\ GFR\;(mL/min) = GFR\;(mL/min/\;1.73 m^2) * BSA / 1.73$$

#### Adjustment Factors for Female Gender

Many equations have an adjustment factor to account for the fact that female patients have less muscle mass, and therefore produce less creatinine. Historically, the Cockcroft-Gault and Jelliffe equations used an arbitrary value of 0.85 or 0.9 as a correction factor, but this value was largely based on empiric estimates with limited data. Fortunately, newer data have shown that this correction factor is actually relatively accurate, with an "optimal" correction factor between 0.84 and 0.88 being the most appropriate for female patients.13

#### Adjustment for Obesity14

Obesity has been a long-standing problem in the estimation of renal function. Serum creatinine production is approximated based on lean body weight because muscle tissue (not fat) is responsible for creatine production. Furthermore, a change in total body mass does not increase the size of the kidney (or GFR) proportionally. Equations that do not correct or adjust for obesity risk overestimation of true renal function.

While there is still significant debate regarding the optimal method of controlling for obesity, it appears that using the Cockcroft-Gault equation with a 40% adjustment is the most appropriate method. In one of the largest study on the topic to date of nearly 3000 overweight and obese patients, the following conclusions can be drawn:14

• Actual body weight will significantly overestimate renal function
• Ideal body weight will significantly underestimate renal function
• The LBW2005 equation, while initially very promising,15,16 significantly underestimates renal function.
• For all classes of obesity (overweight, obese, and morbid obesity), the Cockcroft-Gault equation with a 40% adjustment proved to consistently offer the most accurate estimate of creatinine clearance (often within about 5 mL/min of accuracy)

There are equations that report GFR as a normalized value to body surface area (mL/min/1.73 m2). While these may appear to circumvent the issue of obesity, these values need to be converted to a non-normalized GFR (mL/min) for the purposes of drug dosing. In the process of conversion, however, the non-normalized value will also overestimate GFR in obese patients.

#### Cockcroft-Gault 40% Obesity Adjustment

The most accurate equation for creatinine clearance in obese patients is the Cockcroft-Gault equation with a 40% adjustment factor.14 This equation is most appropriate for patients who are greater than 20-30% of their ideal body weight.17 In essence, this correction accounts for 40% of body mass above a patient's "ideal" body weight:

$$\\ Adjusted\;weight = IdealBW + 0.4*(ActualBW-IdealBW)$$

#### Ideal and Lean Body Weight (Devine 1974 and LBW2005)

Historically, the Devine 1974 equation18 has been used to estimate fat-free, ideal, or lean body weight (all terms generally meaning the same thing). This equation was not scientifically derived or validated,15 but is extensively used in medicine. A newer equation, called LBW200519 may be a more promising estimation of lean body weight and has been derived and validated with actual patient data.

#### Rounding Creatinine in the Elderly

Some practitioners routinely round the serum creatinine of elderly patients (eg, > 60 years) to a value of 1 mg/dL in an effort to control for a reduced muscle mass. Intuitively, this practice does not make sense because rounding a serum creatinine of 0.3 mg/dL (230% increase) is much different than rounding a value of 0.8 mg/dL (25% increase). This practice becomes even more inconsistent when an elderly patient's serum creatinine is already above 1 mg/dL. The literature does not support this practice as it often results in an underestimation of true renal function.20,21 If any correction factor is used, it is likely that a percent adjustment, similar to underweight patients, would be the most appropriate; however, such a correction factor has not been studied in elderly patients.

#### Rounding Creatinine in Underweight Patients

In underweight patients, a low serum creatinine may be more reflective of a decrease in production rather than an increased rate of renal elimination. Similarly to elderly patients, clinicians may be tempted to round creatinine in underweight patients to account for less muscle mass; however, this practice is not supported by the literature.22 The most accurate method to control for underweight patients is to multiply the patient's Cockcroft-Gault value by an adjustment factor of 0.69 (regardless of whether the patient's serum creatinine is above or below 1 mg/dL). This correction factor was shown to be more precise and less bias than rounding or making no adjustment.

#### Medications that Modify Serum Creatinine

Because serum creatinine undergoes tubular secretion, any medications that interfere with this process will falsely elevate the patient's serum creatinine; however, this will not impact the patient's true GFR. The following medications have been shown to falsely elevate serum creatinine:12,20,23

• Cefoxitin
• Cimetidine
• Cisplatin
• Flucytosine
• Trimethoprim

#### Populations who are Difficult to Estimate

Certain patient groups have dramatically different serum creatinine production or elimination compared to the normal patient population. The following groups are notoriously difficult to estimate true renal function:

• Amputation - Falsely low serum creatinine due to less production from muscle mass
• Burn injury - Increased GFR
• Cirrhosis - Falsely low serum creatinine due to less muscle mass and reduced hepatic conversion of creatine to creatinine
• Cystic fibrosis - Increased GFR
• Muscle disorders - Muscular dystrophy and other muscle disorders that can cause cachexia
• Pregnancy - Difficult to estimate lean body mass, increased GFR
• Unstable renal function - Equations used to estimate unstable renal function are very old and not validated in a large patient population

#### Impact of IDMS

There are primarily two laboratory methods for measuring serum creatinine: a number of conventional (older) methods (eg, alkaline picrate), and the newer IDMS method. The conventional methods have a positive bias (falsely elevated by up to 20%) because they detected non-creatinine chromagens.24 The conventional assay method is most susceptible to bias when serum creatinine is within the normal range. The NKDEP guidelines25 recommend that all laboratories convert their systems to use the newer, more accurate IDMS method. According to the NKDEP, almost all laboratories are expected to convert to the IDMS method by the end of 2010.

Note that this calculator automatically converts to and from IDMS as indicated based on the CrCl/GFR equation. All equations before the MDRD equation use non-IDMS creatinine values, the MDRD equation has two equations for either assay, and the CKD-EPI equation is only standardized for IDMS. The following equations are used to convert between IDMS and non-IDMS:26

$$\\ Conventional\;SCr\;(mg/dL) = (IDMS\;SCr)*1.065 + 0.067 \\ IDMS\;SCr\;(mg/dL) = ((Conventional\;SCr)-0.067)/1.065$$

You may specify whether you are entering serum creatinine as an IDMS or 'conventional' assay by clicking the "Config" icon in the top, right-hand corner of the page heading.

### References and Additional Reading

1. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. PMID 1244564.
2. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-12. PMID 19414839.
3. Jelliffe RW. Letter: Creatinine clearance: bedside estimate. Ann Intern Med. 1973;79(4):604-5. PMID 4748282.
4. Salazar DE, Corcoran GB. Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. Am J Med. 1988;84(6):1053-60. PMID 3376975.
5. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1-266. PMID 11904577.
6. Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4):247-54. PMID 16908915.
7. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461-70. PMID 10075613.
8. Jelliffe RW, Jelliffe SM. A computer program for estimation of creatinine clearance from unstable serum creatinine levels, age, sex, and weight. Mathematical Biosciences. 1972;14(1-2):17-24. DOI 10.1016/0025-5564(72)90003-X.
9. Chiou WL, Hsu FH. A new simple and rapid method to monitor the renal function based on pharmacokinetic consideration of endogeneous creatinine. Res Commun Chem Pathol Pharmacol. 1975;10(2):315-30. PMID 1153839.
10. Matzke GR, Millikin SP. Influence of renal function and dialysis on drug disposition. In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring. 3rd ed. Vancouver, WA: Lippincott Williams & Wilkins; 1992:8-6/7.
11. Chow MS, Schweizer R. Estimation of renal creatinine clearance in patients with unstable serum creatinine concentrations: comparison of multiple methods. Drug Intell Clin Pharm. 1985 May;19(5):385-90. PMID 4006730.
12. National Kidney Foundation. Frequently Asked Questions about GFR Estimates. Available at http://www.kidney.org/.../KBA_FAQs_AboutGFR.pdf. Accessed December 18, 2011.
13. Canaday BR, Poe TE, Sawyer WT, et al. Fractional adjustment of predicted creatinine clearance in females. Am J Hosp Pharm. 1984;41(9):1842-3. PMID 6496521.
14. Winter MA, Guhr KN, Berg GM. Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy. 2012;32(7):604-12. PMID 22576791.
15. Pai MP, Paloucek FP. The origin of the "ideal" body weight equations. Ann Pharmacother. 2000;34(9):1066-9. PMID 10981254.
16. Demirovic JA, Pai AB, Pai MP. Estimation of creatinine clearance in morbidly obese patients. Am J Health Syst Pharm. 2009;66(7):642-8. PMID 19299371.
17. Nicolau DP, Freeman CD, Belliveau PP, et al. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. 1995;39(3):650-5. PMID 7793867.
18. Devine BJ. Gentamicin therapy. Drug Intell Clin Pharm. 1974;8:650–655.
19. Janmahasatian S, Duffull SB, Ash S, et al. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051-65. PMID 16176118.
20. Smythe M, Hoffman J, Kizy K, et al. Estimating creatinine clearance in elderly patients with low serum creatinine concentrations. Am J Hosp Pharm. 1994;51(2):198-204. PMID 8160670.
21. Hailemeskel B, Namanny MD, Kurz A. Estimating aminoglycoside dosage requirements in patients with low serum creatinine concentrations. Am J Health Syst Pharm. 1997;54(8):986-7. PMID 9114925.
22. Khuu T, Bagdasarian G, Leung J, et al. Estimating aminoglycoside clearance and creatinine clearance in underweight patients. Am J Health Syst Pharm. 2010;67(4):274-9. PMID 20133531.
23. Lau AH, Berk SI, Prosser T, et al. Estimation of creatinine clearance in malnourished patients. Clin Pharm. 1988;7(1):62-5. PMID 3126017.
24. Spruill WJ, Wade WE, Cobb HH 3rd. Estimating glomerular filtration rate with a modification of diet in renal disease equation: implications for pharmacy. Am J Health Syst Pharm. 2007;64(6):652-60. PMID 17353576.
25. National Kidney Disease Education Program. Chronic Kidney Disease and Drug Dosing: Information for Providers. Available at http://www.nkdep.nih.gov/.../CKD_DrugDosing_508.pdf. Updated January 2010. Accessed December 18, 2011.
26. Ortho-Clinical Diagnostics. Updated Information for IDMS Traceable VITROS® Chemistry Products CREA Slides. June 12, 2008. Written communication available for download.

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Updated Nov 5, 2015
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 Creatinine assay method IDMS Conventional IDMS is the newer, more precise method for measuring serum creatinine. Older methods falsely inflated the creatinine assay by as much as 20%. Most institutions are using IDMS by this point, but you should contacting your laboratory if you are unsure of your assay. For more information, read more about IDMS.
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