pathology tests - urea and creatinine

see also:

• pathology
• renal medicine (nephrology)
• acute kidney injury (AKI) / acute renal failure (ARF)
• chronic renal failure

• 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.
  • see protein metabolism

• most is renally excreted
• some is excreted in sweat and faeces

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

• 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

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

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

• may impair concentrating ability of kidney ⇒ hyponatraemia

• 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 albeit insensitive measure of GFR
• production and excretion of creatinine are reasonably constant
• reference ranges: usually stated to be 53-133umol/L = 0.6-1.5mg/dL in adults

• creatinine is formed from the breakdown of muscle creatine, thus amount produced is proportional to muscle mass and is relatively constant
• plasma levels are ethnically and gender dependent, and are transiently increased by eating cooked meat.
• 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.
  • see protein metabolism

• creatinine is not reabsorbed
• virtually all filtered creatinine appears in urine
• a small amount is secreted by proximal tubules
• urinary creatine is negligible except for:
  • children (occasionally)
  • women during & after pregnancy
  • conditions where there is extensive muscle breakdown eg. starvation, thyrotoxicosis, myopathies

• 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
  • see acute kidney injury (AKI) / acute renal failure (ARF)
• drugs which reversibly inhibit tubular creatinine secretion despite a normal GFR
• creatinine may appear to be falsely elevated in:
  • diabetic ketoacidosis (DKA) due to interference of acetoacetate with automated assays
  • drugs that cross-react in the assay

• 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.
• see also MJA Feb 2009 - debates on the utility of eGFR

• 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

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

• 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

• BCR is the American usage (each in mg/dL) and has a normal range of 8-15 with a cutoff of 20 to signify increased BCR
• UCR is the SI usage with (each in mmol/L) as in Australia and has a normal range of 40-100
• in chronic renal failure, BCR and UCR usually remain in normal range as both urea and CRN excretion are reduced in tandem
• in AKI:
  • pre-renal causes of AKI tend to give a BCR of > 20 and this tends to be a good prognostic sign for AKI unless the patient is critically ill
  • intrinsic renal or post-renal AKI tends to give a BCR of < 20
• a high BCR in cardiac failure patients is a poor prognostic sign

• Plasma urea increased and Plasma creatinine normal
  • Dehydration
  • Heart failure (without renal involvement)
  • Gastrointestinal bleed
    • a BCR > 30 suggests upper GIT bleed, while a BCR of 20-30 suggests lower GIT bleed
  • High-protein diet
  • Catabolic state due to:
    • trauma
    • severe infection
    • starvation
    • corticosteroid drugs
• Plasma urea normal/Plasma creatinine reduced
  • Decreased muscle mass
• Plasma urea disproportionately higher than increased plasma creatinine
  • AKI caused by prerenal mechanisms:
    • shock
    • hypovolemia due to blood loss, vomiting, etc.
    • hypoperfusion due to:
      • cardiorenal syndrome, heart failure
      • severe hypotension

• 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

• URR = [1 – (Postdialysis urea / Predialysis urea)] × 100
• URR > 65 % is widely regarded as indicating adequate dialysis