Estimated GFR Methods

Measurement of GFR

The GFR is a measure of the rate at which water and dissolved substances (low molecular weight, ultrafiltrateable compounds) are filtered out of the blood per unit time. Normal GFR's for males are about of 150 mL/min per 1.73 m2 and 130 mL/min per 1.73 m2 for females. Procedures for determining GFR with high accuracy require the injection of exogenous substances which are known to be only filtered at the glomerulus and not absorbed or secreted by the renal tubules. These "gold standard" procedures include Cr-EDTA, radiological contrast media (Iohexol) and inulin. Procedures determining GFR using exogenous substances are invasive and carry some risk to the patient which usually are considered too expensive and time consuming for routine clinical use. Historically creatinine has been considered the renal marker of choice because it is a naturally occurring endogenous compound that is freely filtered at the glomerulus and has relatively minor absorption and secretion by the renal tubules. Even though serum creatinine determination remains the most commonly used renal marker for estimation of GFR, it is known to have a number of inherent difficulties which limit its clinical reliability.5,6 These include the fact that measurement of GFR by creatinine is influenced by multiple non-renal factors including diet, gender, muscle mass and tubular secretion which can result in an overstatement of GFR up to 20%. In an attempt to improve the accuracy of serum creatinine measurements the NKDEP has advocated the use of GFR estimates calculated from serum creatinine levels. These include the Modification of Diet in Renal Disease (MDRD) and the Cockroft-Gault (CG). In addition a quadratic formula has been introduced by the Mayo Clinic which has been referred to as the Mayo Clinic Quadratic (MCQ). Each of these equations has strengths and weaknesses for use in specific patient sub-populations.

Even though creatinine based GFR equations such as the MDRD improve the accuracy of serum creatinine measurements, concentrations of creatinine can be within the normal range even with a GFR of around 40 mL/min/1.73 m2 resulting in a so called "creatinine blind" range. This is due to the fact that MDRD understates normal and elevated GFR's and overstates decreases in GFR5.

NKDEP Classification
of Kidney Disease

Normal

Healthy kidneys GFR > 90 mL/min per 1.73 m2

Stage 1

Kidney damage with normal or elevated GFR GFR > 90 mL/min per 1.73 m2

Stage 2

Kidney damage and mild decrease in GFR GFR of 60 -89 mL/min per 1.73 m2

Stage 3

Moderate decrease in GFR GFR of 30 – 59 mL/min per 1.73 m2

Stage 4

Severe decrease in GFRGFR <16 – 29 mL/min per 1.73 m2

Stage 5

Kidney failure - End Stage Renal Disease (ESRD) GFR of <15 mL/min per 1.73 m2


Limitations of creatinine as a Marker for GFR

Limitation

Comments

Non-Renal Factors

Gender
Ethnicity
Diet
Muscle mass
Drugs which affect tubular secretion of Creatinine

Clinical Utility

Poor sensitivity for CKD "creatinine blind range"

Serum creatinine remains in the normal range until 50% of renal function is lost. Insensitive to loss of GFR in Stage 2 and Stage 3 of CKD.

Analytical Problems

Non-specific bias frequently reported with the commonly used Jaffé Assay Method (alkaline picrate )

Use of enzymatic assays for creatinine such as Diazyme's enzymatic creatinine method can significantly improve test performance by eliminating many sources of analytical error.