BUN and creatinine are waste products excreted by the kidneys that can indicate renal function. BUN is formed from protein breakdown while creatinine is from muscle metabolism. Both are filtered by the glomeruli and their levels in blood and urine can show if renal function is normal, decreased due to poor blood flow or damage to the kidneys. Renal clearance tests measure how much of a substance is cleared from the blood by the kidneys and help evaluate kidney function. Elevated BUN and creatinine levels often mean impaired renal excretion due to problems with blood flow to the kidneys, obstruction, or direct kidney damage.
BUN and creatinine are waste products excreted by the kidneys that can indicate renal function. BUN is formed from protein breakdown while creatinine is from muscle metabolism. Both are filtered by the glomeruli and their levels in blood and urine can show if renal function is normal, decreased due to poor blood flow or damage to the kidneys. Renal clearance tests measure how much of a substance is cleared from the blood by the kidneys and help evaluate kidney function. Elevated BUN and creatinine levels often mean impaired renal excretion due to problems with blood flow to the kidneys, obstruction, or direct kidney damage.
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BUN and creatinine are waste products excreted by the kidneys that can indicate renal function. BUN is formed from protein breakdown while creatinine is from muscle metabolism. Both are filtered by the glomeruli and their levels in blood and urine can show if renal function is normal, decreased due to poor blood flow or damage to the kidneys. Renal clearance tests measure how much of a substance is cleared from the blood by the kidneys and help evaluate kidney function. Elevated BUN and creatinine levels often mean impaired renal excretion due to problems with blood flow to the kidneys, obstruction, or direct kidney damage.
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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
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.