What the meaning of GFR ?

 Glomerular Filtration Rate (GFR) and Creatinine Clearance (CrCl) in Health and Disease: Using Popular Formulae (September 2009) 

This discussion piece reviews common methods for estimating kidney function. The reader may find it helpful to become re-acquainted with basic renal physiology as that information will not be covered here. 

It is considered good Radiologic practice to screen patients for renal dysfunction prior to the administration of any iodinated or gadolinium-based contrast medium. The American College of Radiology recommends that all practitioners screen patients for renal dysfunction; this can easily be done by questioning the patient or by chart review, looking for a history of renal disease/transplant, diabetes mellitus, long-standing hypertension, diuretics or nephrotoxic drugs, multiple myeloma, hyperuricemia, or advanced age (≥70 years). If renal dysfunction is present or suspected, then laboratory measurements of renal function should be obtained. The US FDA recommends that patient renal function be assessed either by history or laboratory measurements prior to the administration of gadolinium-based contrast agents.

Renal function can be evaluated by obtaining laboratory measurements of blood urea nitrogen (BUN) and serum creatinine (SCr), but neither are sensitive measures of renal function. SCr is influenced by the patient’s gender, muscle mass, nutritional status, and age. GFR is traditionally considered the best overall index of renal function in health and disease. Direct measurement of GFR (or CrCl using the compound inulin) would be the most accurate method of defining renal function, but this requires timed urine collections or radioisotope elimination methods, and thus is difficult to measure in clinical practice. Therefore, most people estimate the GFR from the SCr using specially derived predictive equations.

The GFR may be estimated using several formulae, but the most common are:

• Cockcroft-Gault formula, estimates CrCl in adults
• Schwartz formula, estimates GFR in children under 12 years
• Modification of Diet in Renal Disease, estimates GFR in adults

Cockcroft-Gault equation for estimating GFR (CrCl):

eGFR = [(140-age) X body weight (kg) X 0.85 (if female)] ÷ [72 X SCr (mg/dl)]

The most widely used method for estimating GFR, this equation considers age, sex, body weight, and SCr in estimating GFR. It is thought to more accurately reflect creatinine clearance. This equation was validated in group of normal volunteers (Canadian Mounties) and is considered by some to be inaccurate as renal function decreases.

Schwartz formula for the prediction of GFR in children:

GFR(ml/min per 1.73 m2) = 39.1[height (m)/Scr (mg/dl)]0.516 X [1.8/cystatin C (mg/L)]0.294[30/BUN (mg/dl)]0.169[1.099]male[height (m)/1.4]0.188

Cockcroft-Gault also works well in children.

Modification of Diet in Renal Disease (MDRD) for deriving CrCl (GFR):

eGFR = 186 x SCr-1.154 X (age)-0.203 X (0.742 if female) X (1.210 if black)

The MDRD formula is based on GFR values measured by iothalamate clearance in 1628 adults and subsequently validated in another 1775 adults in the African American study of Kidney Disease. The four-variable MDRD Study equation uses age, sex, race, (African-American vs. non-African-American) and SCr. This equation does not require a body weight because it normalizes GFR for a standard body surface area of 1.73 m2. The MDRD formula has been demonstrated to be useful for chronic kidney disease patients and performs similarly in diabetic and non-diabetic individuals, but its use is unclear in healthy individuals and is not recommended for hospitalized patients. The MDRD formula is the recommended method for estimating GFR among Nephrology specialists.

These formulae are available at several websites and can be downloaded into hand-held computers for easy access. There are also simple cardboard “slide-rule” style calculators available from GE Healthcare, and while these are “low-tech”, they are convenient to use and require no batteries.

RENAL DYSFUNCTION

There is no uniform definition of renal dysfunction. When CrCl is less than 60 ml/min (in a normal young adult equivalent to a SCr of 133 mmol/L or 1.5 mg/dl) the term “renal insufficiency” has been used, and when CrCl is less than 30 ml/min the term “renal failure” is often used.

Discussion: The most accurate results are obtained with the Cockroft-Gault equation, whereas the most precise formula is the MDRD study equation. The predictive capabilities of these formulae are suboptimal for ideal patient care, but are superior for assessing renal function compared to a simple SCr measurement. Recall that a raised SCr implies that GFR has been reduced by at least 50%, making the patient at risk for developing contrast-induced acute kidney injury (CIAKI).

Some investigators have proposed using “cut-off” values for SCr and/or eGFR

Cut-off values: eGFR < 80 ml/min, or
SCr > 1.3 mg/dl (115 µmol/L) for males 
SCr > 1.1 mg/dl (90 µmol/L) for females

eGFR < 60 ml/min, or
SCr > 1.55 mg/dl (137 µmol/L) for males 
SCr > 1.18 mg/dl (104 µmol/L) for females

eGFR < 30 ml/min, or
SCr > 2 mg/dl (177 µmol/L) for males 
SCr > 1.65 mg/dl (146 µmol/L) for females

The use of cut-off levels, especially the low levels, will include several patients with normal renal function and the use of the high levels will exclude patients with renal impairment.

It is the responsibility of each Radiologist or other prescriber to have a protocol in-place to identify patients for CIAKI.  The referring physician must be involved in identifying patients at-risk so the necessary precautions can be taken in time.  A recent SCr level should be obtained in patients with a history of risk factors.  Professional guidelines have been produced and are helpful for crafting local standard procedures.

References:

1. Bostom AG, Kronenberg F, Ritz E  Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels. J Am Soc Nephrol 2002; 13:2140-2144