laboratory evaluation of renal function s.popli. m.d.,f.a.c.p. 7/13/2005
TRANSCRIPT
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Laboratory Evaluation of Renal Function
S .POPLI. M.D.,F.A.C.P.
7/13/2005
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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.
• GPE:BP 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?
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Case 1 continued
• Urine protein /Urine creatinine returns 15mg/150mg ratio(<0.1)
• 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?
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Urine Protein:Categories of persistent proteinuria
• Overflow: Capacity to reabsorb normally filtered protein in proximal tubules over whelmed due to overproduction:e.g.light chains,hemoglobinuria and myoglobinuria
• Tubular proteinuria: Decreased reabsorption of filtered proteins by tubules due to tubulointerstitial damage ; usually <2 gm
• Glomerular proteinuria: Microalbuminuria to overt proteinuria usually>3.5 gm
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Screening for Urine proteinScreening for Urine protein
• Dipstick: Gives green color, does not check for light chainsNegative – 10 mg/dl
Trace – 15-25 mg/dl
1-2+ – 30-100 mg/dl
3+ – 300 mg/dlSulfosalicylic acid: white precipitate
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Urine protein :Quantitative measurement
24 hour collection of urine for protein normal excretion is <150 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 <0.1 . A ratio >3 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
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MicroalbuminuriaMicroalbuminuria
• 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
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Detection of Micro albuminuria: 24 hour urine collection
Detection of Micro albuminuria: 24 hour urine collection
• Normal urine protein excretion : <150mg (20% of this is albumin)
• Therefore, normal urinary albumin excretion is < 30 mg/day
• Microalbuminuria :urinary albumin excretion 30-300 mg/day
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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 <30 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?
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Why and When to Screen Patients for
Microalbuminuria ?
• BP control with Ace_I and ARB’s 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
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Proteinuria Case 2
A70 year- old male is referred for chronic azotemiaPMH: unremarkableGPE: BP120/60 , LE edemaLabs: 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 gmWhat other tests would you order to diagnose cause
of his renal dysfunction ? UPEP,why?
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Clinical Assessment of Renal Function:
Glomerular Filtration Rate(GFR)
Clinical Assessment of Renal Function:
Glomerular Filtration Rate(GFR)
• Parameters used Blood urea nitrogen
Serum creatinine
Endogenous creatinine clearance
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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 < 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
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Blood Urea Nitrogen (BUN)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
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CreatinineCreatinine
• Formed at a constant rate by dehydration of muscle creatine
• Normally 1–2% of muscle creatine is broken into creatinine
• Mol. Wt. 113• Creatinine is freely filtered by the
glomerulii and is not reabsorbed 10–15% is secreted into proximal tubule
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CreatinineCreatinine
• Normal serum level 1–2 mg/dl
• 24 hour creatinine excretion20 mg/kg/day for males
15 mg/kg/day for females
• Children, females, elderly, spinal cord injured have low serum and urine creatinine
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BUN/Creatinine ratio 10:1BUN/Creatinine ratio 10:1
• Normal
• Chronic renal failure
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D/D in Case 3 with BUN Creatinine ratio >10:1• Decreased perfusion
» Hypovolemia» Congestive heart failure
• Increased urea load– GI bleed– Glucocorticoids
-Tetracycline– Hyper catabolic states– High Protein diet
• Obstructive uropathy• Decreased muscle mass
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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
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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: <1%• Urine Sediment: Hyaline casts• What is the cause of < 10: 1 ,BUN to creat ratio
now?
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BUN/Creatinine ratio ‹ 10:1BUN/Creatinine ratio ‹ 10:1
• Decreased urea loadLow protein dietLiver failure
• Inhibition of creatinine secretionCimetidineTrimethoprim Probenecid
– Increased removal: Dialysis
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BUN/Creatinine ratio ‹ 10:1BUN/Creatinine ratio ‹ 10:1
• Increased creatinine loadIngestion of cooked meatRhabdomyolysis
• Interference with creatinine measurementKetosisCefoxitin
• Increased muscle massAnabolic steroidsMuscular development
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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?
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“Dirty Brown” Sediment in ATN
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Urinary Indices in Diagnosis of Acute Renal Failure
Pre renal ATN
Uosm(mosm/kgH20) >500 <350
Urine sodium (mmol/l) <20 >40
Urine/plasma urea nitrogen >8 <3
Urine/Plasma Creatinine >40 <20
Fractional Excretion of Sodium<1% >1%
Sediment normal “dirty brown”
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Fractional Excretion of filtered Sodium(FeNa)
• FeNa= Amount of Na excreted Amount of Na filtered
• FeNa=UNa 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
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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 ?
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Concept of Clearance ? Measurement of GFR by Creatinine
Clearance(Ccr)
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
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GFR Estimation by Plasma CreatinineGFR Estimation by Plasma Creatinine Cockcroft and Gault Formula*Calculated creatinine clearance = (140–age) 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)x7072x2
*Applicable only when patient is in a steady state, not edematous and not obese
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GFR Estimation by Plasma Creatinine(Pcr)
GFR Estimation by Plasma Creatinine(Pcr)
• In steady state
Creatinine excretion = creatinine production=constant
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
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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
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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