pa_ureacrn

pathology tests - urea and creatinine

urea

  • NH2CONH2
  • MW 60.1 ⇒ 1mmol/L = 60mg/L = 6mg/dL BUT measured urea is actually “blood urea nitrogen” so as there are 2 atoms of nitrogen per urea molecule and atomic weight of N is 14, the “MW” of BUN is 28g, thus:
    • 1mmol/L urea = 28mg/L “BUN” = 2.8mg/dL “BUN”
  • urea is primarily formed in the liver (it is also formed in the brain) from ammonium ion which is formed by deamination of amino acids. Ammonium ion is converted to urea via the urea cycle, thus in severe liver disease, urea production falls but ammonia levels rise.

renal handling of urea

  • 10% excretion at low urine flow rates
  • 60% excretion at high urine flow rates
  • cortical collecting duct impermeable to urea

uraemia

causes of raised urea levels

  • decreased urine flow (once glomerular filtrate has been formed renal urea clearance is largely a function of urine flow rate):
    • normal BUN:CRN ratio (and urinary sodium usually > 40mEq/L)
      • renal failure (usually has normal BUN:CRN ratio if uncomplicated)
    • raised BUN:CRN ratio (and urinary sodium < 20mEq/L as tubular reabsorption not damaged)
      • intravascular volume depletion (eg. dehydration)
      • cardiac failure
      • acute urinary obstruction
  • increased urea production (raised BUN:CRN ratio):
    • catabolic states causing increased protein turnover:
      • fever
      • surgery, trauma
      • steroids, tetracycline
      • starvation
      • GIT bleed
    • increased protein intake

effects of raised levels of urea:

  • bone marrow suppression
  • platelet dysfunction
  • nausea
  • altered mental state

decreased serum urea levels

causes of lowered serum urea:

  • pregnancy
  • liver disease
  • low protein diet
  • anabolic state

effects of low urea:

creatinine (CRN)

  • 1mg/dL = 88.7 umol/L (ie. MW must be 112.8) (ie. 1 mmol/L = 11.28mg/dL)
  • usually serum creatinine varies inversely with GFR although creatinine clearance is a more reliable measure of GFR
  • creatinine is formed from the breakdown of muscle creatine, thus amount produced is proportional to muscle mass
  • creatine is synthesized in the liver from methionine, glycine & arginine. In skeletal muscle, creatine is phosphorylated to phosphorylcreatine which is an important energy store for ATP synthesis. ATP formed from glycolysis & oxidative phosphorylation reacts with creatine to form ADP & phosphorylcreatine. During exercise the process is reversed, maintaining a supply of ATP.

creatinine is formed from phosphorylcreatine & thus is not directly formed from creatine.

  • urinary creatine is negligible except for:
  • children (occasionally)
  • women during & after pregnancy
  • conditions where there is extensive muscle breakdown eg. starvation, thyrotoxicosis, myopathies
  • production and excretion are reasonably constant
  • reference ranges: usually stated to be 53-133umol/L = 0.6-1.5mg/dL in adults

aetiology of raised serum creatinine levels

  • increased muscle mass
  • catabolic states
    • muscle diseases eg. rhabdomyolysis may cause serum CRN to rise by more than 2mg/dL/day
  • decreased GFR:
    • under steady state conditions, if GFR is halved then serum creatinine doubles
    • abrupt cessation of glomerular filtration causes serum creatinine to rise by 1-2mg/dL/day
  • drugs which reversibly inhibit tubular creatinine secretion despite a normal GFR
  • creatinine may appear to be falsely elevated in:

estimated GFR (eGFR)

  • an estimation of glomerular filtration rate, derived from the patient’s creatinine result, their age and gender using the MDRD calculator
    • GFR = 186 × (SCR ÷ 88.4)-1.154 × AGE-0.203
    • Females: multiply result by 0.742
  • the eGFR has been found to be at least as reliable an estimate of kidney excretory function as is the 24 hour urine creatinine clearance test, if not better.
  • values above 60 ml/min/1.73m2 are reported as >60.

clinical situations where eGFR results may be unreliable and/or misleading:

  • Acute changes in kidney function (eg. acute kidney failure)
  • Dialysis-dependent patients
  • Exceptional dietary intake (eg. vegetarian diet, high protein diet, creatine supplements)
  • Extremes of body size
  • Diseases of skeletal muscle, paraplegia, those with high muscle mass and amputees
  • Children under the age of 18 years
  • Severe liver disease present
  • eGFR values above 60 mL/min/1.73m2

eGFR has not been validated or shown to have acceptable accuracy in:

  • Aboriginal and Torres Strait Islander peoples
  • Asian populations (including Japanese, Chinese and Vietnamese)
  • Maori and Pacific Islander peoples
  • Calculations for drug dosing

indications for referral to a nephrologist

  • eGFR <30 mL/min/1.73 m2
  • Rapidly declining kidney function (>15% in eGFR over 3 months irrespective of baseline level)
  • Proteinuria >1g/24 hrs
  • Glomerular haematuria
  • Kidney disease and hypertension that proves difficult to control
  • Diabetes and eGFR <60 mL/min/1.73 m2

BUN:CRN ratio

  • in pre-renal or post-renal acute renal failure the BUN:CRN ratio (each in mmol/L) is usually > 40:1 whereas in uncomplicated intrinsic acute renal failure the normal ration of 40:1 is not markedly increased.
  • NB. BUN:CRN(each in mg/dL) of 10:1 is equiv. to ratio of 40:1 (each in mmol/dL)
    • 10x(1/2.8) / 0.0887 = 40.26

creatinine clearance

  • estimate of GFR
  • normal values:
    • males:
      • 140-200 L/day
      • 70 +/- 14 ml/min/m2
      • 1.5-2.0 ml/sec
    • females:
      • 120-180 L/day
      • 60 +/- 10 ml/min/m2
    • much lower values in neonates & infants
  • not useful in detecting early kidney damage due to hypertrophy of residual glomeruli
  • decreases only after > 50% of normal glomerular filtration surface destroyed
pa_ureacrn.txt · Last modified: 2009/02/16 07:13 (external edit)