Glomerular Filtration Rate: Adult
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#### Renal Function Estimation in Adult Patients

Evaluation of a patient's renal function often includes the use of equations to estimate glomerular filtration rate (GFR) (eg, estimated GFR [eGFR] creatinine clearance [ClCr]) using an endogenous filtration marker (eg, serum creatinine) and other patient variables. For example, the Cockcroft-Gault equation estimates renal function by calculating ClCr and is typically used to steer medication dosing. Equations which calculate eGFR are primarily used to categorize chronic kidney disease (CKD) staging. The rate of creatinine clearance does not always accurately represent GFR; creatinine may be cleared by other renal mechanisms in addition to glomerular filtration and serum creatinine concentrations may be affected by non-renal factors (eg, age, gender, race, body habitus, illness, diet). In addition, these equations were developed based on studies in limited populations and may either over- or underestimate the renal function of a specific patient.

Nevertheless, most clinicians estimate renal function using ClCr as an indicator of actual renal function for the purpose of adjusting medication doses. For medications that require dose adjustment for renal impairment, utilization of eGFR (ie, Modification of Diet in Renal Disease [MDRD]) may overestimate renal function by up to 40% which may result in supratherapeutic medication doses (Hermsen, 2009). These equations should only be used in the clinical context of patient-specific factors noted during the physical exam/work-up. Decisions regarding drug therapy and doses must be based on clinical judgment.

#### RENAL FUNCTION ESTIMATION EQUATIONS

Commonly used equations include the Cockcroft-Gault, Jelliffe, four-variable Modification of Diet in Renal Disease (MDRD), and six-variable MDRD (aka, MDRD extended). All of these equations were originally developed using a serum creatinine assay measured by the alkaline picrate-based (Jaffe) method. Many substances, including proteins, can interfere with the accuracy of this assay and overestimate serum creatinine concentration. The National Kidney Foundation and The National Kidney Disease Education Program (NDKEP) advocate for a universal creatinine assay, in order to ensure an accurate estimate of renal function in patients. As a result, a more specific enzymatic assay with an isotope dilution mass spectrometry (IDMS)-traceable international standard has been developed. Compared to the older methods, IDMS-traceable assays may report lower serum creatinine values and may, therefore, overestimate renal function when used in the original equations (eg, Cockcroft-Gault, Jelliffe, original MDRD). Updated four-variable MDRD and six-variable MDRD equations based on serum creatinine measured by the IDMS-traceable method has been proposed for adults (Levey, 2006); the Cockcroft-Gault and Jelliffe equations have not been re-expressed and may overestimate renal function when used with a serum creatinine measured by the IDMS-traceable method. Clinicians should be aware of the serum creatinine assay used by their institution and the ramifications the assay may have on the equations used for renal function estimation.

Regardless of the serum creatinine assay used, the following factors may contribute to an inaccurate estimation of renal function (Stevens, 2006):

- Increased creatinine generation (may underestimate renal function):

  - Black or African American patients

  - Muscular body habitus

  - Ingestion of cooked meats

- Decreased creatinine generation (may overestimate renal function):

  - Increased age

  - Female patients

  - Hispanic patients

  - Asian patients

  - Amputees

  - Malnutrition, inflammation, or deconditioning (eg, cancer, severe cardiovascular disease, hospitalized patients)

  - Neuromuscular disease

  - Vegetarian diet

- Rapidly changing serum creatinine (either up or down): In patients with rapidly rising serum creatinines (ie, increasing by >0.5-0.7 mg/dL/day), it is best to assume that the patient's renal function is severely impaired

Use extreme caution when estimating renal function in the following patient populations:

- Low body weight (actual body weight < ideal body weight)

- Liver transplant

- Elderly (>90 years old)

- Dehydration

- Recent kidney transplantation (serum creatinine values may decrease rapidly and can lead to renal function underestimation; conversely, delayed graft function may be present)

Note: In most situations, the use of the patient's ideal body weight (IBW) is recommended for estimating renal function, except when the patient's actual body weight (ABW) is less than ideal. Use of actual body weight (ABW) in obese patients (and possibly patients with ascites) may significantly overestimate renal function. Some clinicians prefer to use an adjusted body weight in such cases [eg, IBW + 0.4 (ABW - IBW)]; the adjustment factor may vary based on practitioner and/or institutional preference.

##### Alkaline picrate-based (Jaffe) methods

Note: These equations have not been updated for use with serum creatinine methods traceable to IDMS. Use with IDMS-traceable serum creatinine methods may overestimate renal function; use with caution.

Method 1: MDRD equation:

eGFR = 186 X (Creatinine)-1.154 X (Age)-0.203 X (Gender) X (Race)

where:

eGFR = estimated GFR; calculated in mL/minute/1.73 m2

Creatinine is input in mg/dL

Age is input in years

Gender: Females: Gender = 0.742; Males: Gender = 1

Race: Black: Race = 1.212; White or other: Race = 1

Method 2: MDRD Extended equation:

eGFR = 170 X (Creatinine)-0.999 X (Age)-0.176 X (SUN)-0.170 X (Albumin)0.318 X (Gender) X (Race)

where:

eGFR = estimated GFR; calculated in mL/minute/1.73 m2

Creatinine is input in mg/dL

Age is input in years

SUN = Serum Urea Nitrogen; input in mg/dL

Albumin = Serum Albumin; input in g/dL

Gender: Females: Gender = 0.762; Males: Gender = 1

Race: Black: Race = 1.18; White or other: Race = 1

Method 3: Cockroft-Gault equation1

Males: ClCr = [(140 - Age) X Weight] / (72 X Creatinine)

Females: ClCr = {[(140 - Age) X Weight] / (72 X Creatinine)} X 0.85

where:

ClCr = creatinine clearance; calculated in mL/minute

Age is input in years

Weight is input in kg

Creatinine is input in mg/dL

Method 4: Jelliffe equation

Males: ClCr = {98 - [0.8 X (Age - 20)]} / (Creatinine)

Females: ClCr = Use above equation, then multiply result by 0.9

where:

ClCr = creatinine clearance; calculated in mL/minute/1.73m2

Age is input in years

Creatinine is input in mg/dL

##### IDMS-traceable methods

Method 1: MDRD equation2:

eGFR = 175 X (Creatinine)-1.154 X (Age)-0.203 X (Gender) X (Race)

where:

eGFR = estimated GFR; calculated in mL/minute/1.73 m2

Creatinine is input in mg/dL

Age is input in years

Gender: Females: Gender = 0.742; Males: Gender = 1

Race: Black: Race = 1.212; White or other: Race = 1

Method 2: MDRD Extended equation:

eGFR = 161.5 X (Creatinine)-0.999 X (Age)-0.176 X (SUN)-0.170 X (Albumin)0.318 X (Gender) X (Race)

where:

eGFR = estimated GFR; calculated in mL/minute/1.73 m2

Creatinine is input in mg/dL

Age is input in years

SUN = Serum Urea Nitrogen; input in mg/dL

Albumin = Serum Albumin; input in g/dL

Gender: Females: Gender = 0.762; Males: Gender = 1

Race: Black: Race = 1.18; White or other: Race = 1

#### FOOTNOTES

1Equation typically used for adjusting medication doses

2Preferred equation for CKD staging National Kidney Disease Education Program

#### REFERENCES

Cockcroft DW and Gault MH, "Prediction of Creatinine Clearance From Serum Creatinine," Nephron, 1976, 16(1):31-41.[PubMed 1244564]

Dowling TC, Matzke GR, Murphy JE, et al, "Evaluation of Renal Drug Dosing: Prescribing Information and Clinical Pharmacist Approaches," Pharmacotherapy, 2010, 30(8):776-86.[PubMed 20653353]

Hermsen ED, Maiefski M, Florescu MC, et al, "Comparison of the Modification of Diet in Renal Disease and Cockcroft-Gault Equations for Dosing Antimicrobials," Pharmacotherapy, 2009, 29(6):649-55.[PubMed 19476418]

Jelliffe RW, "Letter: Creatinine Clearance: Bedside Estimate," Ann Intern Med, 1973, 79(4):604-5.[PubMed 4748282]

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, 16;130(6):461–70.

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.[PubMed 16908915]

National Kidney Disease Education Program, "GFR Calculators." Available at: http://www.nkdep.nih.gov/professionals/gfr_calculators. Last accessed: January 20, 2011.

Stevens LA, Coresh J, Greene T, et al, "Assessing Kidney Function - Measured and Estimated Glomerular Filtration Rate," N Engl J Med, 2006, 354(23):2473-83.[PubMed 16760447]

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