Serial measurements are used clinically to assess severity and course of renal disease.
ß
GFR = ß renal function (ie, disease)
Ý
GFR = improvement in renal function
stable but subnormal GFR = stable renal disease
Normal value for total kidney GFR =125mL/min men = 115-130 mL/min women = 100-125 mL/min
Necessary for determining drug dose: Patient with renal disease -normal [drug]plasma can accumulate to toxic levels
Clearance
The volume of plasma cleared of a substance by renal excretion
always in units of Volume/time: usually mL/min
Inulin – used to estimate GFR (glomerular filtration rate)
clearance of inulin accurately estimates GFR because (like all GFR markers) it:
achieves stable plasma concentration
is freely filtered at the glomerulus
is not reabsorbed, secreted, synthesized or metabolized by kidney
Therefore the amount of inulin found in urine per unit time reflects the amount of inulin filtered from plasma per unit time. (Filtered inulin = Excreted inulin)
If plasma inulin concentration is known, then the volume of plasma filtered per unit time (GFR) can be calculated as follows: GFR =urine inulin concentration X urine volume over time / plasma inulin concentration
Cinulin (GFR) is measured by infusing inulin and measuring plasma and urine inulin levels and urine volume per unit time
is completely secreted from the pertitubular capillaries to the proximal tubules
Cx = [X]urine x V/[X]plasma
X = any molecule
Clearance of any molecule relative to inulin describes renal handling of that compound
Cx = Cinulin
no net reabsorbtion or secretion of x
Cx < Cinulin
net reabsorption of x (ie, urea)
Cx > Cinulin
net secretion of x
Creatinine Clearance
: Common clinical estimate of GFR: Creatinine is an endogenouse marker (less cumbersome)
Ccreatinine determined using venous blood creatinine concentration and 24 hr urine collection for V and urine creatinine concentration
Creatinine derives from creatine metabolism in the skeletal muscle (relatively constant production)
Is basically not reabsorbed or synthesized at the kidney
Ccr is only an estimate of GFR: several factors introduce error (ie, small amount of Cr is secreted by tubules)
Has stable plasma levels: Crexcretion= Crproduction at Steady State (SS)
Is freely filtered at the glomerulus: GFR x [Creatinine]plasma = Constant; therefore
ß GFR Þ Ý [Cr]Plasma until new SS
The inverse relationship between GFR and [Cr]plasma is a somewhat insensitive indicator of GFR
1.4mg/dl is considered a normal [Cr]plasma level. However, due to
Ý tubular secretion and hyper filtration of creatinine in renal disease many patients present with [Cr]plasma near this range inspite of greatly reduced GFRs (40-80ml/min).
Creatinine secretion becomes saturated at [Cr]plasma above 1.5-2 mg/dl. therefore [Cr]plasma rise as expected with further decreases in GFR