Blood urea nitrogen (BUN) concentration is poorly correlated with GFR. Since urea is highly permeable to renal tubules, urea clearance varies with urine flow rate: at urine flow rates of less than 30 mL/h, urea clearance is as low as 30 percent of GFR and, with urine outputs greater than 100 mL/h, urea clearance can increase to 70 to 100 percent of GFR. Ihis relation is used clinically to help differentiate prerenal failure from other etiologies of ARF. In prerenal conditions, low urine flow rates favor BUN reabsorption, out of proportion to creatinine (Cr). Ihis results in a disproportionate rise of BUN to relative creatinine, creating a serum ratio of BUN/Cr that is greater than 20 in prerenal failure.
BUN concentration depends on both nitrogen balance and renal function. BUN concentration can rise significantly with no decrement in GFR by increases in urea production with protein loading, trauma, or gastrointestinal bleeding. Corticosteroids and tetracycline increase BUN by decreasing tissue anabolic rates. Basal BUN concentration can be severely depressed by malnutrition or advanced liver disease. Baseline BUN concentration should be estimated when attempting to correlate changes in BUN with GFR. For example, in a cirrhotic patient with a BUN of 12 mg/dL, a normal range GFR might be assumed, but only with the knowledge of a baseline BUN of 4 mg/dL does the real decrease in GFR become apparent.
Serum creatinine provides the most accurate and consistent estimation of GFR, yet the proper use of creatinine in gauging changes in GFR requires knowledge of its production and clearance.
Creatinine is the breakdown product of the skeletal muscle protein, creatine. Creatinine production is linked to muscle mass, which in turn depends on lean body weight, age, and gender. Muscle mass is a greater percentage of body weight in males and decreases with age.
Variations in muscle mass have important implications in using creatinine to estimate GFR. GFR declines by 1 percent a year after the age of 40 years, but serum creatinine remains unchanged because the decline in GFR is balanced by decreasing muscle mass with age. Ihis implies that older patients have lower GFRs than younger patients with the same serum creatinine. Ihe following formula attempts to compensate for these effects of body weight, age, and gender on the correlation between creatinine and GFR:21
Some diseases and medications can interfere with the correlation of serum creatinine with GFR. Acute glomerulonephritis causes increased tubular secretion of creatinine; this falsely depresses the rise in serum creatinine. Irimethoprim, cimetidine, and salicylates all cause decreased creatinine secretion, falsely elevating creatinine with no change in GFR.
A possible error may occur according to the laboratory method used to measure creatinine. Ihe most commonly used method uses alkaline picurate. Ihis method is also called the total chromogen method because it measures all serum chromogens: creatinine plus glucose, fructose, uric acid, acetone, acetoacetate, protein, ascorbic acid, pyruvate, and cephalosporins. At normal serum levels, these noncreatinine chromogens constitute only 5 to 20 percent of the total chromogens. In conditions such as diabetic and isopropyl ketosis, elevations of acetone and acetoacetate falsely elevate serum creatinine. High levels of bilirubin with this method falsely indicate a low creatinine level.
Ihe imidohydrolase method is an enzymatic method for measuring creatinine, which resolves the problem of noncreatinine chromogens and bilirubin with the picurate method. However, the imidohydrolase method has been shown to report falsely high creatinine levels in the presence of high glucose and the antifungal agent flucytosine.
Ihe rate of increase in serum creatinine can be used to estimate GFR. In patients with no renal function (GFR = 0), serum creatinine will increase 1 to 3 mg/dL/day. Lessor increases in serum creatinine indicate remaining renal function (GFR) and larger increases indicate excessive muscle breakdown (e.g., rhabdomyolysis). Under stable conditions, serum creatinine correlates with GFR (Tablelll88:10).
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