A 58-year-old man comes to the emergency department due to generalized weakness, anorexia, and nausea for the past several weeks. He also reports lower extremity swelling but has had no dyspnea or chest pain. The patient was diagnosed with hypertension several years ago but did not follow up and takes no medications. Blood pressure is 182/100 mm Hg and pulse is 84/min. Physical examination shows pitting edema of the bilateral lower extremities. Laboratory studies reveal elevated serum creatinine and blood urea nitrogen levels. During evaluation of renal dysfunction, total urinary creatinine is measured over a 24-hour period, and creatinine clearance is calculated using the serum and urine creatinine concentrations and urinary volume. Compared to the calculated creatinine clearance, this patient's true glomerular filtration rate is most likely to be:
This patient with elevated creatinine and blood urea nitrogen levels has symptoms of uremia (eg, weakness, nausea, anorexia) due to kidney disease, most likely from chronic uncontrolled hypertension.
Kidney filtration function is reflected by the glomerular filtration rate (GFR), which is the sum of the filtration rates of all the nephrons in the kidneys. Normal GFR ranges between 120 and 130 mL/min per 1.73 m2 of body surface area, and can vary considerably based on age, sex, and body habitus. GFR is reduced in both chronic kidney disease (due to loss of functional nephrons) and acute kidney injury (eg, due to decreased renal perfusion).
The GFR can be directly measured using an ideal filtration marker that is freely filtered across the glomerulus and is not metabolized, secreted, or reabsorbed by the kidney tubules. However, this is time intensive and invasive and requires multiple blood draws. In addition, the substance previously used to perform these calculations, inulin, is no longer available in the United States.
Because of the limitations in directly measuring GFR, renal filtration function is more commonly estimated using creatinine, a waste product generated from the breakdown of creatine in the muscles. Creatinine is released from muscle at a relatively constant rate and is neither metabolized nor reabsorbed by the kidney. However, in addition to passive filtration, a portion of creatinine is actively secreted by the proximal tubules. Therefore, uncorrected creatinine clearance overestimates the GFR by approximately 10%-20%. Creatinine clearance has further limitations in patients with low muscle mass (eg, malnutrition, lower extremity amputation) or high- or low-protein diets.
(Choices A, C, D, and E) Creatinine clearance overestimates the GFR by 10%-20% due to the proximal tubular secretion of creatinine.
Educational objective:
Glomerular filtration rate (GFR) can be assessed using an ideal filtration marker that is freely filtered across the glomerulus and is not metabolized, secreted, or reabsorbed by the kidney tubules. In common practice, GFR is estimated using creatinine clearance. However, creatinine is actively secreted by the proximal tubules, so uncorrected creatinine clearance overestimates the GFR by approximately 10%-20%.