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Laboratory Evaluation of Renal Function

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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


1
Laboratory Evaluation of Renal Function
  • S .POPLI. M.D.,F.A.C.P.
  • 7/13/2005

2
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?

3
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
    nephropathy?

4
Urine ProteinCategories of persistent
proteinuria
  • 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

5
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

6
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

7
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

8
Detection of Micro albuminuria 24 hour urine
collection
  • 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

9
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?

10
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
    presentation

11
Proteinuria Case 2
  • A70 year- old male is referred for chronic
    azotemia
  • 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?

12
Clinical Assessment of Renal Function Glomerular
Filtration Rate(GFR)
  • Parameters used
  • Blood urea nitrogen
  • Serum creatinine
  • Endogenous creatinine clearance

13
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
    0.5
  • 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

14
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
    tubule
  • BUN level is related to Renal function, protein
    intake, and liver function

15
Creatinine
  • Formed at a constant rate by dehydration of
    muscle creatine
  • Normally 12 of muscle creatine is broken into
    creatinine
  • Mol. Wt. 113
  • Creatinine is freely filtered by the glomerulii
    and is not reabsorbed
  • 1015 is secreted into proximal tubule

16
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17
Creatinine
  • 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

18
BUN/Creatinine ratio 101
  • Normal
  • Chronic renal failure

19
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

20
Pathophysiology of Pre-renal Azotemia in Case 3
  • Decreased Effective Intravascular
    ADH
  • Volume
  • Renal Hypoperfusion activation of RAS
  • Diminished GFR aldosterone
  • Low urine volume and U sodium and high Uosmolality

21
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
    started
  • 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
    now?

22
BUN/Creatinine ratio 101
  • Decreased urea load
  • Low protein diet
  • Liver failure
  • Inhibition of creatinine secretion
  • Cimetidine
  • Trimethoprim
  • Probenecid
  • Increased removal Dialysis

23
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

24
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
    hours.
  • 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?

25
Dirty Brown Sediment in ATN
26
Urinary Indices in Diagnosis of Acute Renal
Failure

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

27
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

28
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 ?

29
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
  • Pcr.mg/dl
  • Normal GFR 100 ml/min
  • GFR declines by 1 ml/min/year after age 40

30
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

31
GFR Estimation by Plasma Creatinine(Pcr)
  • In steady state
  • Creatinine excretion creatinine
    productionconstant
  • Creatinine excretion Urine creatinine x Urine
    volume
  • 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
    GFR
  • GFR1/2 X 2 Pcr GFR x Pcr constant
  • A rise in Pcr almost always represents a fall in
    GFR

32
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
    same

33
Summary
  • How to evaluate a patient with renal disease
  • How to interpret u/a,urine protein to creatinine
    ratios
  • Interpretation of urea nitrogen and creatinine
    ratios
  • 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
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