2004A13 Describe the concept of renal clearance and its use to estimate glomerular filtration rate.

· Intro: clearance, ideal tracer

· Tracer comparison

Renal clearance

· Hypothetical volume of plasma from which substance is completely removed per unit time

· Clearance = [X]_u / [X]_p x urine flow rate

· Normal renal plasma flow 600mL/min

· Normal glomerular filtration rate 120mL/min

· Filtration fraction 0.2

Ideal tracer

Clearance of a substance can be used to estimate GFR if:

· Freely filtered, not reabsorbed or secreted or metabolized

· Inert, non-toxic

· Does not affect renal function

Clearance of this substance = GFR

Inulin	· Fructose polymer · Freely filtered, not secreted, not reabsorbed · Method: insert urine catheter, IV infusion until steady state, measure concentrations and urine output · Gold standard for measurement of GFR
Creatinine	· Metabolite of sarcoplasmic creatine kinase · Freely filtered, 10% secreted in health, not reabsorbed · Methods: o 24 hour urine collection o Cockroft-Gault equation: CrCl = [(140 – age) x LBW] / (SCr x 72) x 0.85 if female o CKD-EPI equation (for eGFR): age, sex and SCr o MDRD equation: age, sex, race, SCr · Problems: o GFR can fall by 50% before significant ↑[creatinine] o Renal failure -> ↑secreted fraction -> overestimation of GFR o ↓Muscle mass -> ↓SCr -> overestimation of GFR
Urea	· End-product of amino acid de-amination · Renal handling: o Freely filtered, 50% reabsorbed o Same 50% secreted into thin descending limb of the loop of Henle o Same 50% reabsorbed at medullary collecting duct (i.e. urea recycling) · Problems: o GFR can fall by 50% before significant ↑[urea] o Dehydration or high protein intake -> ↑[urea] -> underestimation of GFR
PAH	· Para-aminohippuric acid: glycine amide of PABA · Freely filtered, secreted, not reabsorbed · i.e. used to measure renal plasma flow
Glucose	· Freely filtered, almost 100% reabsorbed (unless >10mM)