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Laboratory Evaluation of Renal Function


Transient albuminuria may occur with fever,infection,exercise,decompensated CHF ... US done shows 6 cm abdominal aortic aneurysm, she undergoes resection with cross ... – PowerPoint PPT presentation

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Title: Laboratory Evaluation of Renal Function

Laboratory Evaluation of Renal Function
  • S .POPLI. M.D.,F.A.C.P.
  • 7/13/2005

Proteinuria Case 1
  • A 20 year old patient is referred to you for ,he
    has been diabetic for 6 years ,he was told to
    have some kidney problem by his MD.He wants to
    know the cause of renal dysfunction.
  • GPEBP 145/90 ,otherwise exam is normal
  • How would you proceed ?
  • BUN 15mg/dl, creatinine 1.0mg/dl ,U/A shows SG
    1.024 ,trace protein ,a few hyaline casts
  • What test would you order next ?
  • 24h protein collection , U protein/U creatinine
    ratio or both?

Case 1 continued
  • Urine protein /Urine creatinine returns
    15mg/150mg ratio(lt0.1)
  • Does this patient have abnormal proteinuria ?
  • Patient wants to know if he has microalbuminuria
    ,you order urine micro albumin result is 60mg
    micro albumin /gm creatinine .
  • Is this abnormal, does this patient have diabetic

Urine ProteinCategories of persistent
  • Overflow Capacity to reabsorb normally filtered
    protein in proximal tubules over whelmed due to
    overproductione.g.light chains,hemoglobinuria
    and myoglobinuria
  • Tubular proteinuria Decreased reabsorption of
    filtered proteins by tubules due to
    tubulointerstitial damage usually lt2 gm
  • Glomerular proteinuria Microalbuminuria to overt
    proteinuria usuallygt3.5 gm

Screening for Urine protein
  • Dipstick Gives green color, does not check for
    light chains
  • Negative 10 mg/dl
  • Trace 15-25 mg/dl
  • 1-2 30-100 mg/dl
  • 3 300 mg/dl
  • Sulfosalicylic acid white precipitate

Urine protein Quantitative measurement
  • 24 hour collection of urine for protein normal
    excretion is lt150 mg/24 hour
  • Spot urine protein/urine creatinine ratio (as
    24 h urine creatinine excretion is a function of
    muscle mass i.e. 15 mg/kg for females and 20mg/kg
    for males ) a normal ratio is 150/1500 or lt0.1 .
    A ratio gt3 indicates nephrotic range proteinuria
  • Case 1 has normal urine protein excretion, trace
    protein on u/a is due to highly concentrated
    urine ,pt may still have microalbuminuria

  • Urine albumin excretion below detection by
    regular dipstick
  • First clinical sign of diabetic nephropathy
  • Incidence increases with the duration of diabetes
    and may be present at the diagnosis of NIDDM
  • Transient albuminuria may occur with
    fever,infection,exercise,decompensated CHF
  • Associated with poor glycemic control and
    elevated BP

Detection of Micro albuminuria 24 hour urine
  • Normal urine protein excretion lt150mg (20 of
    this is albumin)
  • Therefore, normal urinary albumin excretion is lt
    30 mg/day
  • Microalbuminuria urinary albumin excretion
    30-300 mg/day

Microalbuminuria Detection by Spot Urine Albumin
to Urine Creatinine ratio
  • Easier than cumbersome 24 hr.collection
  • If we assume daily creatinine excretion to be
    1000 mg and normal urine albumin excretion lt30
    mg albumin / creatinine ratio should be less
    than 0.03 or 30mg/g creatinine
  • Thus case 1 has micro albuminuria which is likely
    due to diabetic nephropathy.How would you manage
    him now?

Why and When to Screen Patients for
Microalbuminuria ?
  • BP control with Ace_I and ARBs have been known
    to reduce microalbuminuria and delay the
    progression of kidney disease in diabetics
  • IDDM patients should be screened yearly,beginning
    5 years after the onset of disease
  • Patients with NIDDM should be screened at

Proteinuria Case 2
  • A70 year- old male is referred for chronic
  • PMH unremarkable
  • GPE BP120/60 , LE edema
  • Labs U/A SG 1.010 pH 6.0 , protein neg, glucose
    2, Uprotein /U creatinine ratio 4
  • BUN 30mg/dl creat.3.0, Blood Sugar 78mg/dl
    albumin 2.8, Hb 10 gm
  • What other tests would you order to diagnose
    cause of his renal dysfunction ?
  • UPEP,why?

Clinical Assessment of Renal Function Glomerular
Filtration Rate(GFR)
  • Parameters used
  • Blood urea nitrogen
  • Serum creatinine
  • Endogenous creatinine clearance

Case 3 Azotemia
  • A 55 year old diabetic female is admitted with
    intractable vomiting and low urine output
  • Exam BP 120/60 with postural hypotension
  • Labs BUN 60, Creat. 2.0 mg/dl ( baseline
    1.0mg/dl), Hb 16gm
  • ,U/A SG 1.020, sediment hyaline casts,UNa 10
    mmol/L,UOsm 600 mosm/kg,Ucreat.150mg/dl ,Fe Na lt
  • Q.What is the cause of her high BUN to creatinine
    ratio and her renal failure? What are the
    other causes of high BUN to creatinine ratio

Blood Urea Nitrogen (BUN)
  • Catabolism of aminoacids generates NH3
  • NH2
  • 2 NH3 CO2 C 0 H2O
  • NH2
  • Urea Mol wt 60
  • BUN Mol wt. 28
  • Normal BUN 10-20 mg/dl
  • After filtration 50 is reabsorbed by the
  • BUN level is related to Renal function, protein
    intake, and liver function

  • Formed at a constant rate by dehydration of
    muscle creatine
  • Normally 12 of muscle creatine is broken into
  • Mol. Wt. 113
  • Creatinine is freely filtered by the glomerulii
    and is not reabsorbed
  • 1015 is secreted into proximal tubule

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  • Normal serum level 12 mg/dl
  • 24 hour creatinine excretion
  • 20 mg/kg/day for males
  • 15 mg/kg/day for females
  • Children, females, elderly, spinal cord injured
    have low serum and urine creatinine

BUN/Creatinine ratio 101
  • Normal
  • Chronic renal failure

D/D in Case 3 with BUN Creatinine ratio gt101
  • Decreased perfusion
  • Hypovolemia
  • Congestive heart failure
  • Increased urea load
  • GI bleed
  • Glucocorticoids
  • -Tetracycline
  • Hyper catabolic states
  • High Protein diet
  • Obstructive uropathy
  • Decreased muscle mass

Pathophysiology of Pre-renal Azotemia in Case 3
  • Decreased Effective Intravascular
  • Volume
  • Renal Hypoperfusion activation of RAS
  • Diminished GFR aldosterone
  • Low urine volume and U sodium and high Uosmolality

Case 3 Diabetic patient continued..
  • Vomiting stopped ,BP improved and BUN/creat
    lowered to 35/1.8mg/dl. 24 hours later she
    developed UTI, trimethaprim/sulfamethoxazole was
  • Next day 24 hr urine output 800 mL
  • Exam Unremarkable
  • BUN 20 mg/dl Creat 3.0 mg/dl
  • Uosm 600 mosm/kg ,UNa 10 mom/l, FeNa lt1
  • Urine Sediment Hyaline casts
  • What is the cause of lt 10 1 ,BUN to creat ratio

BUN/Creatinine ratio 101
  • Decreased urea load
  • Low protein diet
  • Liver failure
  • Inhibition of creatinine secretion
  • Cimetidine
  • Trimethoprim
  • Probenecid
  • Increased removal Dialysis

BUN/Creatinine ratio 101
  • Increased creatinine load
  • Ingestion of cooked meat
  • Rhabdomyolysis
  • Interference with creatinine measurement
  • Ketosis
  • Cefoxitin
  • Increased muscle mass
  • Anabolic steroids
  • Muscular development

Case 3 continued… 6 months later
  • Pt was discharged with normal BUN and
    creatinine,6 months later she is admitted with
    vague abdominal pain, an US done shows 6 cm
    abdominal aortic aneurysm, she undergoes
    resection with cross-clamping of aorta for 2
  • Post surgery she is oliguric (u/o less than 70ml
    in 8 hours).On exam well hydrated.
  • U/A SG 1.015 ,Dirty brown sediment U Na 40
    mEq /L U osmolality 350 mOsm/l ,Fe Na 2
  • What is your diagnosis after reviewing the lab
    data ? How would you manage?

Dirty Brown Sediment in ATN
Urinary Indices in Diagnosis of Acute Renal

  • Pre renal ATN
  • Uosm(mosm/kgH20) gt500 lt350
  • Urine sodium (mmol/l) lt20
  • Urine/plasma urea nitrogen gt8 lt3
  • Urine/Plasma Creatinine gt40
  • Fractional Excretion of Sodiumlt1 gt1
  • Sediment normal
    dirty brown

Fractional Excretion of filtered Sodium(FeNa)
  • FeNa Amount of Na excreted
    Amount of Na filtered
  • FeNaUNa x Urine volume
    PNa x GFR
  • FeNa UNa x V
  • PNa x(UCr x V) /PCr
  • FeNa UNa x PCr X 100
  • PNa x UCr

Case 4
  • 20 y/o male is seen at West point ,on admission
    physical wt 70Kg , BUN 10mg/dl, serum
    creatinine 1.0mg/dl, GFR was 100ml/min and he
    excreted 1500mg creatinine /day in the urine. 2
    months later he develops acute glomerulonephritis
    with RBC and fatty casts.His serum creatinine
    increases to 2mg/dl and remains at 2mg/dl at 1
    year follow up .Wt is 72kg
  • What is his estimated GFR by Cockcroft and Gault
    formula and by serum creatinine?
  • What would be the creatinine excretion now at 1
    year ?

Concept of Clearance ? Measurement of GFR by
Creatinine Clearance(Ccr)
  • Urine is collected for 24 hours and plasma
    creatinine is measured the next day
  • 1. Filtered creatinine Excreted creatinine
  • 2. GFR x Pcr Ucr x Volume
  • 3. GFR Ucr. mg/dl x V ml
  • Normal GFR 100 ml/min
  • GFR declines by 1 ml/min/year after age 40

GFR Estimation by Plasma Creatinine
  • Cockcroft and Gault Formula
  • Calculated creatinine clearance
  • (140age) x wt (kg)
  • 72 X serum creatinine(mg/dl)
  • For females, subtract 15 (or multiply by 0.85)
    for paraplegics multiply by 0.8, for
    quadriplegics, multiply by 0.6
  • Est GFR for this pt is ..
  • (140-20)x70
  • 72x2
  • Applicable only when patient is in a steady
    state, not edematous and not obese

GFR Estimation by Plasma Creatinine(Pcr)
  • In steady state
  • Creatinine excretion creatinine
  • Creatinine excretion Urine creatinine x Urine
  • Filtered creatinine GFR x Plasma creatinine
  • As creatinine production is a function of muscle
    mass and remains constant
  • Thus plasma creatinine values vary inversely with
  • GFR1/2 X 2 Pcr GFR x Pcr constant
  • A rise in Pcr almost always represents a fall in

In case 4 ,serum creatinine increased from from 1
to 2 mg/dl and remained at that level, his
24urine creatinine will remain the same
  • Another example 70 kg man with serum creat. of
    1 mg/dl and GFR of 100 ml/min was excreting 1500
    mg creatinine/day,if you remove his one kidney ,
    next day his GFR will be 50ml/min,urine
    creatinine excretion will be 750 mg /day.Over the
    next few days creatinine will accumulate in the
    blood and level will increase to 2 mg /dl and
    thus filtered and excreted amount will be the

  • How to evaluate a patient with renal disease
  • How to interpret u/a,urine protein to creatinine
  • Interpretation of urea nitrogen and creatinine
  • Estimation and measurement of GFR to see when a
    patient would need renal replacement therapy
  • Interpret urine indices in evaluation of various
    causes of ARF