Recently, the National Kidney Foundation published 15 clinical practice guidelines on chronic kidney disease. Their work shows that approximately 11% of the U.S. adult population have chronic kidney disease, which is defined as either kidney damage (i.e., persistent proteinuria) or decreased kidney function (i.e., decreased GFR) for 3 or more months. Adverse outcomes of chronic kidney disease, such as development of kidney failure and cardiovascular disease, can often be prevented or delayed through early detection and treatment.
Guideline 4 relates to the laboratory determination of GFR. Several points are worthy of discussion:
- "Clinicians should not use serum creatinine concentration as the sole means to assess the level of kidney function." Since serum creatinine concentration is affected by factors other than GFR (e.g. relative state of hydration, creatinine secretion and generation, and extrarenal excretion), there is a relatively wide range of values in normal persons. GFR must decline to about half the normal level before the serum creatinine value rises above the upper limit of the reference range. In the elderly, the age-related decline in GFR is not reflected in the serum creatinine because of the age-related decline in muscle mass that reduces creatinine generation.
- "Physicians should estimate the level of GFR from predictive equations that take into account the serum creatinine concentration and some or all of the following variables: age, sex, race and body size. The Modification of Diet in Renal Disease (MDRD) study and Cockcroft-Gault equations provide useful estimates of GFR in adults."
To aid in this recommendation, our Clinical Laboratory will calculate and report estimated GFR for every serum/plasma creatinine test performed on adults using the following MDRD study equation:
GFR (mL/min/1.73 m2) = 186 x (Creat.)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American)
The MDRD study equation has many advantages. It is more accurate and precise than other equations, particularly for persons with a GFR less than 90 mL/min/1.73m2. It predicts GFR as measured by an accepted method (urinary clearance of 125I-iothalamate). It was developed on a large database containing persons with various kidney diseases and was tested on a validation database containing more than 500 additional patients. Current studies are underway to validate the equation in a variety of ethnic groups, persons with diabetes and people with normal renal function. It has not been validated in children.
A GFR value less than 60 mL/min/1.73m2 represents loss of half or more of the adult level of normal kidney function. Below this level, the prevalence of complications of chronic kidney disease increases. Thus a GFR value of 60 has been considered the cutoff for the reference range, and values below this will be flagged as abnormal on our reports. In addition, the MDRD equation includes a patient's race (African-American or non-African American), and since this is often not available to the Clinical Lab, values for GFR will be reported for both.
- "Autoanalyzer manufacturers and clinical laboratories should calibrate serum/ plasma creatinine assays using an international standard." Our assay is a kinetic alkaline picrate (Jaffe) reaction similar to that used in the MDRD study and calibrated to National Institute of Standards and Technology (NIST).
- "Measurement of creatinine clearance by using timed (e.g., 24-hour) urine collections does not provide more accurate estimates of GFR than do predictive equations." In the MDRD study, the estimated GFR calculation provided a more accurate estimate of GFR than measured creatinine clearance. The guidelines recommend obtaining 24-hour urine collections only for special clinical circumstances; these include extremes of age and body size, diseases of skeletal muscle, paraplegia or quadriplegia, strict vegetarian diet, and rapidly changing kidney function. The guidelines are completely silent on the use of Cystatin C. One small study of 112 patients in Finland (Clin Chem 2003;49:1223-5) concluded that estimated GFR based on Cystatin C determinations were very similar to those from the MDRD study equation. While one study does not a trend make, it is worth considering that Cystatin C is a fairly new test and its place in the testing armamentarium for kidney disease is in evolution.
For more details on all of the guidelines, please see the following references:
- Ann Intern Med 2003;139:137-47. National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification.
- Am J Kidney Dis 2002;39:S1-246. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Kidney Disease Outcome Quality Initiative.
Barry P. Latner, M.D.