PREDICTION OF GLOMERULAR FILTRATION RATE (GFR)

The GFR is considered the best overall index of renal function. Urinary clearance of inulin or radioactive markers provide an accurate measurement of GFR, but these methods are cumbersome and not readily available. Instead, the creatinine clearance is generally used for determining GFR. As it involves a 24hr urine collection, it is unfortunately time-consuming and prone to errors.

Many clinicians rely on the serum creatinine concentration as an indicator of GFR. The accuracy of this estimate ishowever limited, because the serum creatinine concentration is affected by factors other than GFR, e.g. muscle mass, dietary intake, drugs, ketosis, extra-renal excretion and renal tubular secretion. Serum creatinine is also aninsensitive index of decreased GFR - the serum creatinine level generally does not rise above the laboratory reference range before the GFR is reduced by 50%. Many individuals with decreased GFR may therefore have a serum creatinine level within the normal range.

Several formulas have been developed which incorporate age, sex and body size together with the serum creatinine concentration, yielding a GFR estimate which is considerably more accurate and precise than when using serum creatinine alone.

Formula / Information required
Cockroft-Gault / S-creat, age, sex, weight
MDRD / S-creat, s-urea, s-alb, age, sex, race
Abbreviated MDRD / S-creat, age, sex, race
Schwartz / S-creat, height, age, sex

Which equation to use?

In adults, the MDRD, Abbreviated MDRD and Cockroft-Gault equations are all endorsed by the National Kidney Foundation.

The Cockroft-Gault formula was developed to predict creatinine clearance. It was derived from 24hr urine creatinineclearance as gold standard. Of the subjects,96% were male and no information on race was given. It is reported that the Cockroft-Gault equation tends to overestimate the GFR and results appear more widely dispersed than with the MDRD equation.

The MDRD was developed from the Modification of Diet in Renal Disease Study data. Radioactive marker clearance was used as the gold standard. GFR is expressed per 1.73m2 of body surface area. Of the subjects, 60% were male and12% were black. Evaluation studies report that this equation seems to underestimate the GFR, but better precision is obtained compared to Cockroft-Gault.

Anabbreviated MDRD equation was also published, using only serum creatinine, for cases where albumin and urea are not available. Results correlate well with the original MDRD calculation.

The equations above are only applicable to adults. In children, the Schwartz formula should be used, based on serum creatinine and height.

Limitations

The GFR prediction equations assume that the patient is in a steady state and that the average rate of creatinine production can be estimated.

Therefore, the equations will be unreliableif the level of GFR is rapidly changing, if muscle mass is unusually high or low or if dietary creatinine intake is unusually high or low. A creatinine clearance is therefore necessary to estimate GFR in the following conditions: pregnancy, obesity, malnutrition, paraplegia, muscle wasting, amputation, vegetarian diet, creatine supplements.

Prediction equations also do not perform well inpeople with normal or mildly impaired renal function.

Creatinine clearance would probably provide a more accurate estimate of GFR in these cases too.

Interpretation

In patients with chronic kidney disease, the stage of disease can be assigned based on the level of kidney function, as estimated by the MDRD equation:

STAGES OF CHRONIC KIDNEY DISEASE
Stage / Description / GFR (ml/min/1.73m2)
1 / Normal /  90
2 / Mild  in GFR / 60 – 89
3 / Moderate  in GFR / 30 – 59
4 / Severe  in GFR / 15 – 29
5 / Kidney failure / < 15

Implementation

The National Kidney Foundationstrongly recommends the use of GFR prediction equations to improve the GFR estimating ability of serum creatinine results. These calculations have now been implemented in our laboratory. As the MDRD requires albumin and urea, and the Cockroft-Gault requires weight, these calculationsneed to be requested specifically. The abbreviated MDRD will be reported with routine creatinine results, if the age and sex of the patient are available.

References

Ann Intern Med. 1999;130:877-84

NKF K/DOQI Guidelines 2002

Pediatrics 2003;111:1416-21

J Am Soc Nephrol. 2003;14:2573-80

Compiled by dr E Hitchcock

July 2005