Interpreting the estimated glomerular filtration rate in primary care: Benefits and pitfalls

Chronic kidney disease is most often discovered and diagnosed by primary care providers. The equations for estimating the glomerular filtration rate (GFR) facilitate earlier detection of this disease. However, the estimated GFR must be interpreted in the context of the individual patient. The diagnostic criteria and staging of chronic kidney disease must be understood so that it can be recognized and managed at the earliest possible stage. In this way, primary care physicians and nephrologists can better coordinate the care of these patients.

THE STAGES OF RENAL DISEASE AND THE GFR

Before 2002, an organized approach to the clinical management of patients with renal dysfunction was hampered by a lack of a standardized way to define this condition. This changed when the National Kidney Foundation, through the Kidney Disease Outcomes Quality Initiative (K/DOQI),¹ defined the stages of chronic kidney disease based on the GFR as estimated by the Modification of Diet in Renal Disease (MDRD) equation.^2,3

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This system has increased the recognition of chronic kidney disease by the health care community and the general public. But the entire system hinges on the utility, accuracy, and reliability of the equations used to estimate the GFR.

In this article, we review the concepts of renal clearance and how to interpret the GFR in healthy patients and in those with chronic kidney disease. The following cases illustrate the interpretation of GFR in the context of patient care.

CASE 1: A 60-YEAR-OLD WOMAN WITH A ‘NORMAL’ CREATININE LEVEL

A 60-year-old white woman with no significant medical history has routine laboratory tests done as part of her annual physical examination. She weighs 135 pounds (61.2 kg) and is 64 inches (163 cm) tall. Her serum creatinine level is 1.1 mg/dL; her estimated GFR is 53 mL/min/1.73 m². A urine dipstick test for protein and blood is normal.

CASE 2: PROTEINURIA WITH A PRESERVED GFR

A 20-year-old African American man with no medical history is undergoing routine blood testing. His serum creatinine level is 1.1 mg/dL; his estimated GFR is reported as “> 60 mL/min/1.73 m²” (calculated at 109 mL/min/1.73 m²). He is 72 inches (183 cm) tall and weighs 180 pounds (83.0 kg); he lifts weights four times a week. Urine dipstick testing reveals 3+ proteinuria.

SERUM CREATININE: AN IMPERFECT MARKER OF KIDNEY FUNCTION

Of the various functions of the kidney, the ability of the glomeruli to filter the blood, as assessed by the GFR, is considered the best index of overall kidney function.^4,5 The GFR can be thought of as the clearance of a substance from the plasma by the kidney in a period of time. This is useful because no method is available to routinely and directly measure filtration across the glomerular basement membrane.

Substances that are cleared by the kidney are used to estimate the GFR. The ideal substance for this estimate is one that is cleared only by filtration and not through metabolism or excretion by other means.

The urinary clearance of the exogenous substance inulin is considered the gold standard method, but radioisotopes such as iothalamate and other markers have replaced inulin in clinical laboratories. Because these methods are expensive, time-consuming, and not widely available, alternative methods that use endogenous markers such as creatinine have been developed for clinical practice.

The serum creatinine concentration possesses many of the qualities of an ideal marker for estimating kidney function. Creatinine is produced by the body at a relatively constant rate under normal conditions and is easy and inexpensive to measure. However, it has several limitations:

• 

  Data presented in Rolin HA III, et al. Evaluation of glomerular filtration rate and renal plasma flow. In: Jacobson HR, et al, eds. The Principles and Practice of Nephrology. St. Louis: Mosby-Year Book 1995:8-13.

  Its clearance does not solely reflect glomerular filtration because the renal tubules also excrete it into the urine.⁶ As a result, creatinine clearance (see below) will tend to overestimate the GFR (Figure 1).
• The serum creatinine concentration is directly dependent on muscle mass, which varies with sex (women tend to have less muscle mass as a percent of body weight than men), age (muscle mass decreases with age), and race (African Americans have a higher serum creatinine level for the same GFR than other Americans).⁶ Thus, there is no “normal” value for serum creatinine that applies to all patients.
• 
  Other factors can alter the creatinine level without changing the GFR, such as changes in dietary protein intake, exercise, and drugs such as cimetidine⁷ and fibrates⁸ (Table 1).

Another important point is that the relationship between the serum creatinine concentration and the GFR is parabolic.⁹ At high kidney function, large changes in the GFR are reflected by very small changes in serum creatinine—the GFR must fall quite a bit before the serum creatinine level rises very much (points A to B in Figure 1). At lower kidney function, small changes in GFR are reflected by large changes in serum creatinine (points C to D in Figure 1). This phenomenon can cause physicians to view small changes in creatinine as unimportant in patients with creatinine levels in the normal or near-normal range. Conversely, small changes may be due to random error inherent in the methods of measuring creatinine rather than to changes in kidney function.

Because the serum creatinine concentration by itself may be misleading when estimating GFR, the National Kidney Foundation and the National Kidney Disease Education Program recommend that it not be used on its own to estimate kidney function.