Creatinine & Renal Function

Clearance:

• Renal clearance = vol of plasma completely cleared of a given substance by the kidneys per unit time (ml/min)
• Involves: glomerular filtration, secretion, reabsorption, and rarely tubular metabolism
• Renal clearance = V x [U]/[P]
  • V = volume of urine or urine flow rate in ml/min
  • [U] = urinary concentration of substance in mg/ml
  • [P] = plasma concentration of substance in mg/ml
    

Estimating GFR:

• GFR = renal clearance of a substance if it is:
  • Freely filtered at glomerulus
  • Not secreted
  • Not reabsorbed
  • Not synthesized
  • Not metabolised
• The amount excreted in the urine = amount filtered
• i.e. [plasma] x GFR = [urine] x urine vol
• Rearrange: GFR = urine vol x [urine] / [plasma]

Creatinine

• used to approximate GFR as is more practical
• Released at a steady state from skeletal muscle cells (phosphocreatine)
• Freely filtered + not reabsorbed.
• *Small amount secreted → overestimates GFR by small amount
• Serum creatinine levels can be used as a surrogate marker of GFR
• Creatinine clearance calculation better than creatinine levels
• most accurate to collect urine and use the formula to assess creatinine clearance
• because serum creatinine it is at steady state, eGFR can be calculated by Cockroft-Gault, MDRD or CKD-Epi
• During acute changes in GFR, serum creatinine will underestimate GFR until a new steady state is reached.

Creatinine Clearance Estimation from Serum Creatinine

• CG (Cockcroft-Gault Equation): common method which has a correlation of ~0.83 with CrCl:
  • CrCl = [(140−A) × W x S)] / (72 × Cr) , where:
    • Cl = Clearance (mL/min), A = Age, W = Lean body Wt (kg)
    • S = Sex coefficient (Male = 1, Female = 0.85), Cr = Creatinine in µmol.L^-1
• Alternative formulas are MDRD and CKD-EPI. These equations have two advantages over Cockcroft-Gault:
  • They are better predictors of GFR
  • They do not require weight, and so can be calculated by the laboratory automatically, Other required data (gender, race, age, creatinine) can be taken from hospital records.
• MDRD (Modification of Diet in Renal Disease Study): useful in estimating glomerular filtration rate (GFR) in stable chronic kidney disease
• CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration): more precise formula to estimate glomerular filtrate rate (GFR) from serum creatinine and other readily available clinical parameters, especially at when actual GFR is >60 mL/min per 1.73m2

Limitations

• General limitations
  • Dependent on serum creatinine, which can be highly variable. Formulas are derived from average values of dependent variables, and so will be unreliable at extremes of:
    • Age
    • Muscle mass
    • Critically ill
    • Malignancy
    • Diet (High production with red meat)
  • the relationship between creatinine clearance and serum creatinine is non-linear
  • fi­ltration is only one component of a complex kidney, although GFR is used as a surrogate of function
  • Small amount of creatinine is secreted by proximal tubule – so Creatinine clearance is ~10-20% higher than GFR
    • More severely overestimates GFR in patients with very low GFR
• Critically ill patients
  • the amount of creatinine produced varies with muscle mass, nutrition, steroid use, muscle injury
  • there can be a decline of almost 50% of function before serum creatinine levels rise
  • they do not indicate dynamic changes in renal function
  • are modified by aggressive fluid resuscitation

JC 2019

Answer by JC