Glomerular Filtration Rate Estimation

Chronic kidney disease (CKD) is defined as: persistent proteinuria (urine albumin/creatinine ratio of greater than 30 mg/g in an untimed urine) or a reduced glomerular filtration rate (GFR less than 60 mL/min/1.73 m2).

The most common causes of CKD are diabetes mellitus, hypertension, and glomerulonephritis. Certain racial groups (African-American) and ethnic groups (Hispanics or Latinos regardless of race) are at increased risk.

A variety of treatments are available to slow the progression of kidney disease. For type 1 diabetics, strict control of blood glucose concentrations has been shown to limit the development of microalbuminuria. Patients with hypertension benefit from treatment with angiotensin converting enzyme (ACE) inhibitors.

Most laboratories measure kidney function by measuring serum creatinine and 24-hour creatinine clearance. Creatinine is a by-product of muscle turnover. Human beings produce a relatively constant amount of creatinine per day that is dependent on muscle mass. In general, men and women produce roughly 20 (range 14-26) and 15 (range 11-20) mg of creatinine per kg of body weight per day, respectively. Gender difference is related to the lower proportion of muscle typically found in females.The prototypical 70 kg man would be expected to produce 70 kg × 20 mg/kg/day or 1400 mg creatinine/day, while a 70 kg woman would produce 70 × 15 or 1050 mg creatinine/day.

Because creatinine is filtered through the glomerulus and not appreciably re-absorbed or secreted by the kidney tubules, serum creatinine level reflects the glomerular filtration rate (GFR). The more blood that is filtered through the kidneys, the more creatinine that is excreted from the body, and the lower the serum creatinine level.. Conversely, the less blood that is filtered, the less creatinine excreted, and the higher the serum creatinine level.

Recent studies have shown that serum creatinine level used in combination with other variables is an excellent predictor of GFR.Among the best known of these equations is the Cockroft-Gault equation,which has been in existence for many years:

GFR = {[140 - Age(yrs)] × Weight(kg)} / (72 × Pcr) × (0.85 if female)

This equation is not widely used because laboratories rarely know the patient’s weight.

The National Kidney Foundation recommended replacing the Cockroft-Gault equation with the Modification of Diet in Renal Disease (MDRD) equation. This equation uses four parameters: serum creatinine level, age, sex, and ethnic group (i.e., whether the patient is African-American or not). As shown below, the equation is quite complicated, involving two exponential terms:

GFR (mL/min/1.73 m2) = 186 × (Pcr)-1.154× (Age)-0.203 × 0.742 (if female) × 1.210 (if African-American)

There are a number of things to notice about this MDRD equation. First, even though creatinine production is dependent on muscle mass, body weight is not included in the MDRD equation. The reason the equation works despite this omission is that values are normalized by being reported as "per 1.73 m2” (an average body surface area).

Secondly, the 186 multiplier at its beginning of the equation has no physiologic significance; it was derived empirically. Third, for any given age and serum creatinine level, the estimated GFR is the same until corrections are applied for being female and/or for being African-American. There can be more than a 1.5-fold range in estimated GFR based on gender and race. Black men have the highest multiplier (1.210), and non-black women have the lowest (0.742).

Information about a patient’s ethnic group may not be readily available. This can be overcome by including values for both African-American and non-African-American patients in a single report, with the clinician being responsible for choosing the correct value for the patient in question. At this time, little guidance is available on how values should be interpreted for a patient of mixed ethnic background.

The National Kidney Foundation recommends reporting GFRs should be reported as above 60 mL/min/1.73 m2. Values below 60 mL/min/1.73 m2 are considered indicative of chronic kidney disease and should indicate the actual number. Population mean GFR varies with age as shown in the following table.

Age (years)

Average GFR (mL/min/1.73m2)

20-29

116

30-39

107

40-49

99

50-59

93

60-69

85

70+

75

Because of the high prevalence of early kidney disease in the general population and because of the evidence that early intervention can prevent or delay adverse outcomes, the recommendation of the National Kidney Foundationis that patients in high-risk groups for developing CKD be screened. Specifically, they recommend a spot urine for albumin/creatinine ratio and a serum creatinine level. These high-risk groups include the following:

  • Patients with diabetes
  • Patients with hypertension
  • Patients over the age of 60
  • Patients who have used non-steroidal anti-inflammatory drugs in the past year
  • Patients with a family history of kidney disease

Any patient who is identified as having a value less than 60 mL/min/1.73 m2 should have a complete evaluation for renal disease performed by his or her physician. Once the GFR falls below 30 mL/min/1.73 m2, the patient should be seen in conjunction with a nephrologist.

Values for both African American and non-African American individuals are reported for each patient. Values less than 60 mL/min/1.73 m2 are consistent with chronic kidney disease and values less than 15 mL/min/1.73 m2 are consistent with kidney failure.