renal clearance / excretion

see also:

• renal physiology
• renal medicine (nephrology)
• urinalysis
• pathology tests - urea, creatinine, eGFR, creatinine clearance, etc

• there are a variety of ways to assess renal excretion rates of a substance

• absolute renal clearance refers to the volume of plasma cleared of a substance by the kidneys over unit time
• eg. normal renal clearance rate of uric acid in a healthy adult is typically 6 to 12 mL/min

absolute clearance (mL/min) = urine concentration of substance x urine output rate (mL/min) / plasma concentration of substance

• the calculated rate of excretion via the kidneys for a substance
• eg. for uric acid with a clearance of 12mL/min and a serum concentration of 8.0 mg/dL, ~57mg would be excreted each hour

excretion rate (mg/hr) = absolute clearance (ml/min) x 60 x serum concentration of substance (mg/dL)

• percent of body content of substance eliminated per hour

k_e(percent per hour) = absolute clearance (L/hr) / volume of distribution (Vd) (L)

volume of distribution (Vd) (L) = fractional Vd/kg x lean body weight (kg)

elimination half-Life in hours = 0.693 / k_e(percent per hour)

• this is the fraction of filtered substance which is excreted into the urine (many substances are significantly re-absorbed)
• eg. for uric acid fractional excretion is usually only 7-12%

fractional clearance (%) = (urine concentration of substance x serum concentration of creatinine) / (urine concentration of creatinine x serum concentration of substance)

• the fraction of renal plasma flow that is filted by the glomeruli

filtration fraction = glomerular filtration rate (GFR) / renal plasma flow rate (RPF)

• normal serum concentrations generally range from 3.4 to 7.2 mg/dL (0.20–0.43 mmol/L) in men
• uric acid poorly crosses cell membranes hence volume of distribution (Vd) = 0.2-0.3L/lean body weight in kg = 14-21L for an average 70kg adult
• GIT bioavailability of purines is ~60%
• every 1mg of base purines yields roughly 1.2mg of uric acid
• a 300g steak plus a beer gives ~450mg purines of which ~270mg is absorbed and metabolized which gives about 324mg uric acid
• assuming 324mg uric acid is absorbed, the expected rise in serum levels would be = 324mg / 17L = 19mg/L = 1.9mg/dL
• a renal clearance of 12mL/min for uric acid (upper limit normal range) with serum levels of 10mg/dL would give a uric acid excretion rate of 72mg/hr and thus take the kidneys several hours to reduce serum uric acid levels back to normal after this spike (actually longer as does not take into account endogenous production rate and even longer if impaired renal function, concomitant alcohol or a larger intake)