BUN and CREATININE • Electrochemical approach

VOLTAIRE C. YABUT, M.D. DPSP  rate of inc. conductivity (NH4+ &

HCO3)
UREA  potentiometric (NH4+ selective
• major excretory product of protein catabolism electrode)
• 45% of total NPNs
Normal Values
• Liver --- CO2 & NH3- (Ornithine or Kreb’s
Henseleit Cycle) • blood: 8-20 mg/dL (2.8-7.1 mmol/L)
• 90% --- kidneys; 10% --- GIT & skin • urinary excretion: 17-20 g/24h
• 25 gm of total urinary solids
CREATINE
• 80-90% of total urinary N
• conc. is affected by: • main storage cmpd of high energy PO4
o renal function & perfusion • Arg, Gly, Met
o dietary protein intake • Muscle --- 98% of total creatine pool
o level of protein metabolism • filtered by glomeruli but completely reabsorbed
• N intake & state of hydration > renal fxn by prox tubules
• BUN:Crea • looses water --- cyclized creatinine
• inc. level --- Azotemia • inc. serum conc --- ske M necrosis/atrophy,
trauma, muscular dystrophies,
Prerenal Azotemia poliomyelitis,myasthenia gravis, starvation
• inadequate perfusion --- diminished filtration • methyltestosterone use, hyperthyroidism,
• CHF, shock, dehydration, hemorrhage, diabetic acidosis, puerperium
diminished blood volume, • measured by the difference in creatinine before
• High protein diet, muscle wasting, & after conversion of creatine to creatinine ---
heat
glucocorticoid Tx, fever, stress, burns
Normal Values
Renal Azotemia
• serum
• primarily diminished glomerular filtration
 0.2-0.6 mg/dl (15-45 umol/L) – males
• acute & chronic renal failure, GN, tubular
necrosis, interstitial nephritis, pyelonephritis  0.6-1.0 mg/dl (45-76 umol/L) – females
• urinary excretion
Postrenal Azotemia  0-40 mg/24h (0-0.35 mmol/24h – males
• UT obstruction --- inc. in back diffusion of urea  0-100 mg/24h (0-0.88 mmol/24h) -
from renal tubules into circulation females
• nephrolithiasis, prostatic hypertrophy, GUT
tumors CREATININE
• once formed can’t be reused --- waste
Uremia • K excretory rate, 1.6-1.7% of T creatinine ---
• clinical syndrome with marked inc. levels of proportional to M mass
urea + acidemia & electrolyte imbalance • freely filtered by glomerulus but not
• N/V, anemia, altered mentation reabsorbed
• in excess of 100 mg/dl – 200 mg/dl --- deep • inhibited by cimetidine, probenecid, TMP
stupor to coma • serum conc is affected by: renal handling,
pregnancy, DM, CRF
Low Levels of Urea • elevated serum crea --- dec GFR --- impaired
• poor nutrition, high fluid intake renal fxn
• pregnancy, severe liver impairment, intake of
anabolic hormones Measurement
1. Jaffe Rxn – treatment w/ alkaline picrate solution ---
Direct Method bright orange-red complex
• Fearon Rxn --- direct condensation w/ diacetyl • chromogens: glucose, fructose, ascorbic acid,
monoxime + strong acid = yellow diazine pyruvate, uric acid
derivative • inc in T°, pH changes
• simple, no interference w/ NH3- • bilirubin, Hgb, lipemic specimens --- neg
• caustic chemicals • Fuller’s earth or Lloyd’s reagent --- remove
interference
Indirect Method • hemolyzed, icteric, lipemic specimens
• Berthelot Rxn • acetoacetate, acetone, barbiturates,
 Urease --- NH4+ & HCO3 phenolsulfonphthalein, sulfobromophthalein,
 NH4+ + nitroprusside --- indophenol protein
• Coupled Enzymatic Rxn
 NH4+ --- coupled rxns --- H2O2 + 2. Coupled Enzymatic Methods
phenol & 4-aminophenazone – quinone- • crea amidohydrolase & crea deaminase --- crea
imine dye cleaving enz
 • H2O2 + phenol derivative + dye --- color
product Urea
• major end product of protein & nucleic acid
3. HPLC metabolism
• high specificity • 80% of N excreted
• deproteinization • reabsorption & filtration
• time consuming • not reliable estimate of GFR --- ingestion,
catabolism, GI losses
Normal Values • inc. --- excess production, diminished renal
 serum blood flow (prerenal causes); UT obstruction
 0.6-1.2 mg/dl (53-106 umol/L) - males (postrenal cause); parenchymal renal damage
 0.5-1.0 mg/dl (44-88 umol/L) – females (true renal cause)
 0.3-1.0 mg/dl (26.5-88.4 umol/L) - <12
 T crea excretion Urea Clearance Test
 1.0-2.0 g/24h (8.8-17.6 mmol/24h) – • infrequently used
males
 0.6-1.5 g/24h (5.3-13.2 mmol/24h) - Methods of Measuring Urea
females 1. Indirect
• generates NH+4 from urea --- urease
• NH+4 is coupled w/ glutamate
dehydrogenase --- converts A-
RENAL FUNCTION TESTS ketoglutarate to Glu w/ NADH as
• serum urea & creatinine cofactor --- measured
spectrophotometrically
• urinalysis
2. Direct
• GFR
• Condensation of urea w/ a diacetyl grp
• clearance studies --- chromogen measured
spectrophotometrically
RENAL CLEARANCE STUDIES
• vol of serum/plasma that contained the
measured subs excreted into urine per unit of
time
• serum clearance is proportional to total # & BUN as an indicator of RF
size of glomeruli, w/c is proportional to renal • BUN:crea --- 10:1-20:1
parenchymal mass • renal parenchymal damage --- maintained
• RBF must be appropriate • inc. ratio --- compromised bld flow --- low urine
• glomerular filtration must be adequate flow rate (dehydration, CHF, hepato-renal
• renal tubular function should be normal syndrome, UT obstruction, GI bleeding, fever)
• no significant obstruction to urine outflow • dec. ratio --- low CHON diet, pregnancy, chronic
hemodialysis
Creatinine
• cyclized form of creatinine Renal Clearance
• related to muscle mass  General Clearance Formula in mL/min =
• affected by ingestion of sterilized canned Urine substance in mg/dL x Volume in
meats mL/min Serum substance in mg/dL
• active tubular secretion --- counterbalanced by
reabsorption in tubules  Clearance in mL/min/std. surface area =
Urine substance x Urine Volume x
Creatinine Clearance 1.73m2 Serum Substance
• N GFR --- crea clearance exceeds inulin A
clearance by 5-10%
• dec. GFR --- crea clearance is largely composed  Creatinine Clearance = denotes GFR
of tubular secretion Urine Creat in mg/dL x Urine Volume in
• glomerular filtration is inc. in NS mL/min Serum Creat in mg/dL
• drug interference
Urine Creat x Urine Volume x 1.73m2
Methods of Measuring Creatinine Serum Creat 1440 A
I. Jaffe Reaction  Where 1440 = number of
• colorimetric determination --- complex minutes/24 hrs
of creatinine w/ picric acid  1.73m2 = BSA of an average
II. Ektachem Chemistry Analyzer normal person
• enzymatic degradation of creatinine w/  A = BSA from a normogram
creatinase
• NH+4 + Bromphenol Blue ---  Estimated Creatinine Clearance
reflectance spectrophotometry
  Cockcroft & Gault (1976) with  Creatinine
correction for age and weight; results  Jaffe reaction
reported in mL/min  Elevated with primary renal disease
Males = (140-age) x Weight in  Uric Acid
kg (72 x  Uricase method
Serum Creat in mg/dL)  Elevated with renal disease,
hyperuricemia
Females = (140-age) x Weight in  BUN = 1/GFR
kg (0.85 x Serum Creat in  BUN:Creatinine ratio = NV 10:1 to 20:1
mg/dL)  Abnormal:
 >20:1 = Prerenal low
 NV males 90-139 females perfusion
80-125
 10:1 to 20:1 = Renal
slight impairment 52--62.5
moderate impairment 28 – 42
mild impairment 42–52 severe
impairment < 28

 Renal Failure Index (RFI) =

Urine Na in mEq/L x Serum Creatinine in
mg/dL Urine Creatinine in
mg/dL
 Interpretation
 RFI <= 1: prerenal azotemia
 RFI =1-3: less definitive but
usually indicates tubular
necrosis
 RFI >= 3: acute tubular
necrosis

 Functional Excretion of Sodium (FENa)

Na Clearance x 100
Creatinine Clearance

Urine Na x Serum Creat x 100

Urine Creat x Serum Na

Renal Function & Nitrogen Balance FE-Na < 1% FE-Na > 1%

 Nonprotein Nitrogenous compounds =
 Urea (45%) • 10% of cases of nonoliguric • most cases of ATN
 Amino acids (20%) ATN • after diuretic administration
 Uric acid (20%) • pre-renal azotemia • pre-existing chronic renal
 Creatinine (5%) • acute glomerulonephritis failure
 Creatine (1-2%) • early acute urinary tract • diuresis due to mannitol,
obstruction glycosuria, bicarbonaturia
 Ammonia (0.2%)
• early sepsis
 Urea as Blood Urea Nitrogen
 Enzymatic assay of NH3 most common
 Elevated with primary renal disease
Stages of Chronic Progressive Renal Disease
Stage Renal Function Serum Creatinine Serum BUN
Remaining (mg/dL) (mg/dL)

Decreased renal 50-75 1.0-2.5 15-30

reserve

Renal insufficiency 25-50 2.5-6.0 25-60

Renal failure 10-25 5.5-11.0 55-110
Factors Affecting Creatinine Clearance
• Sex: normally less in women than men.
• Age: lower in children, until the age of 2. It
decreases in 0-10
Uremic syndrome adults with age, starting
>8.0 at age 80
(ESRD) 20.
• Muscle mass: Decreased in elderly; changes
also noted in myopathies and cachexia.
• Pregnancy
• Hyperglycemia: Due to osmotic diuresis and
body fluid redistribution.
• Morbid obesity or marked ascites excrete less
creatinine/kg than expected
• Proteinuria: increases creatinine clearance.
• Time of day: It is highest in afternoon.