Blood Urea Nitrogen and Creatinine

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Blood urea nitrogen (BUN) is a byproduct of protein metabolism and is produced by the liver. The reference range for BUN level is 7 to 18 mg/dL. A rise in BUN can be seen with worsening renal function. However, an elevated BUN level is not specific for intrinsic renal disease and can be seen with prerenal causes of azotemia such as hypovolemia and congestive heart failure, postrenal causes of obstructive nephropa-thy, and gastrointestinal bleeding. At low flow rates, the renal tubules will increase reabsorption of urea, thereby elevating BUN proportionately more than creatinine. BUN can also be reduced in severe liver disease, malnutrition, the syndrome of inappropriate antidiuretic hormone secretion (SIADH), or occasionally the third trimester of pregnancy.

Creatinine is a product of muscle metabolism, and production is related to muscle mass, age, gender, and race, and dietary meat intake. Creatinine is filtered by the glomerulus and secreted by the proximal tubule. Creatinine levels increase as renal function is reduced. At normal renal function, most of the urinary creatinine excretion is from glomerular filtration, with about 5% to 10% from tubular secretion. As the glomerular filtration rate (GFR) declines, a larger proportion of creatinine excretion comes from secretion; therefore, direct measurements of creatinine clearance overestimate GFR with progressive reductions in renal function. Some drugs, including cimetidine, trimethoprim, fenofibrate, salicylates, and pyrimethamine, can block the secretion of creatinine and falsely elevate creatinine levels, particularly in the setting of a low GFR. Although serum creatinine has long been used to estimate renal function, current guidelines from the National Kidney Foundation recommend using estimated GFR (eGFR) from serum creatinine to report kidney function. Many clinical laboratories now automatically report the eGFR using the Modification of Diet in Renal Disease (MDRD) equation. This equation uses age, serum creatinine, and gender to estimate the GFR, expressing GFR in mL/min/1.73 m2. Limitations of the eGFR include lack of standardization of cre-atinine assays in different laboratories and underestimation of GFR in healthy persons. In addition, the equations were developed in persons with chronic kidney disease and may not accurately calculate GFR in elderly, nonwhite, or healthy persons (Stevens and Levey, 2005).

The BUN/creatinine ratio can help differentiate prerenal and postrenal causes of renal insufficiency from intrinsic renal disease. Ratios of 10:1 suggest intrinsic renal pathology; ratios greater than 20:1 suggest prerenal or postrenal causes.

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