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

Quantifying Renal Clearance


  • 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


  • Small 194 Da anion, H2O soluble
  • Freely filtered
  • But also secreted by PCT cells
  • Secretion rate is saturable (TMAX)


  • 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

Creatinine Clearance for GFR

  • 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

Limitations of Creatinine

  • 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!