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 volume

·  Normal renal plasma flow 600mL/min

·  Normal glomerular filtration rate 120mL/min

·  Filtration fraction 0.2

Ideal tracer

·  Freely filtered, not reabsorbed or secreted or metabolized

·  Inert, non-toxic

·  Does not affect renal function

Clearance of this substance = GFR


Tracer comparison


·  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


·  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


·  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


·  Para-aminohippuric acid: glycine amide of PABA

·  Freely filtered, secreted, not reabsorbed

·  i.e. used to measure renal plasma flow


·  Freely filtered, almost 100% reabsorbed (unless >10mM)



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