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.

• 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?

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?

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

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

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

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

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

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?

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

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?

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

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

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

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

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

BUN/Creatinine ratio 10:1BUN/Creatinine ratio 10:1

• Normal

• Chronic renal failure

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

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

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?

BUN/Creatinine ratio ‹ 10:1BUN/Creatinine ratio ‹ 10:1

• Decreased urea loadLow protein dietLiver failure

• Inhibition of creatinine secretionCimetidineTrimethoprim Probenecid

– Increased removal: Dialysis

BUN/Creatinine ratio ‹ 10:1BUN/Creatinine ratio ‹ 10:1

• Increased creatinine loadIngestion of cooked meatRhabdomyolysis

• Interference with creatinine measurementKetosisCefoxitin

• Increased muscle massAnabolic steroidsMuscular 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 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?

“Dirty Brown” Sediment in ATN

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”

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

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)

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

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

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

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

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