H4ii: Describe the utility of measurement of serum Creatinine and estimation of Creatinine Clearance

Fick Principle

Renal clearance is based on the FICK PRINCIPLE which is the conservation of mass

DELIVERY (artery) = RETURN (vein) x EXCRETION (urine)

Renal clearance is the volume of plasma completely cleared of a substance per unit of time
Units = volume per unit time
- g. 5mg of a substance is excreted per hour
- 5mg of a substance exists in 200mL of plasma
- ∴clearance is 200mL/hr
- 200mL of volume has been completely cleared of a substance
Clearance is important because it pertains to one of the kidney’s major functions à removing waste

Gold standard of measuring renal clearance
Starch polysaccharide of 5000 Da
∴freely filtered, not absorbed ∴not excreted, not metabolised or synthesised by renal tubules
∴all inulin filtered into Bowman’s capsule appears in the urine

Protein of 5800 Da
Freely filtered → but taken up almost entirely by PCT cells → ∴ clearance <1mL/min

End product of creatine metabolism
Released into blood continuously by skeletal m.
Muscle mass is constant ∴level is constant
Freely filtered, not reabsorbed, small amount is secreted
- Patient 24hr urine collection
- Plasma creatinine taken
- Applied to clearance formula to yield creatine clearance

GFR is the sum of filtration rates for all kidneys
∴given an index of kidney function
Creatinine gives an estimate of GFR because it is freely filtered, not reabsorbed, synthesised or metabolised. It is secreted & gives a bit of an overestimated GFR
Advantages
- Endogenous & already at steady state
- Unlike insulin which needs to be infused over time to give steady state
Disadvantages
- Searched by PCT ∴CrCl will overestimate GFR
- Some drugs affect the secretion of creatinine
- Annoying to collect a 24hr urine sample
In practise it is more normal to measure PLASMA CREATININE alone
Used as an indicator of GFR e. an estimate of an estimate!
Normal plasma CrT = 1mg/dL
When GFR ↓plasma Crt ↑
But this relationship is non-linear & even at 50% nephron function plasma crt has only ↑slightly
∴predicting GFR from a single creatinine is pretty inaccurate
But monitoring the trend over time is useful to monitor progression of renal disease

Creatinine varies with muscle bulk
Requires correction for size, weight & sex e. by COCKCROFT-GAULT formula
In ICU many patients at risk of developing AKI
Often we do not know their baseline Crt & we have to use reference Crt (from admission)
But many factors in ICU affect patient’s Crt Cl & plasma Crt
- Muscle bulk ↓
- Variable renal haemodynamics
- Altered volumes of distribution
- Many confounding variable to an already inaccurate measurement of GFR!