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.
GPE:BP 145/90 ,otherwise exam is normal
How would you proceed ?
BUN 15mg/dl, creatinine 1.0mg/dl ,U/A shows SG ,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(<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?

4. 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

5. Screening for Urine protein
Dipstick: Gives green color, does not check for light chains
Negative – 10 mg/dl
Trace – mg/dl
1-2+ – mg/dl
3+ – 300 mg/dl
Sulfosalicylic acid: white precipitate 27

6. 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

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 : <150mg (20% of this is albumin)
Therefore, normal urinary albumin excretion is < 30 mg/day
Microalbuminuria :urinary albumin excretion 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 <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?

10. 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

11. Proteinuria Case 2 A70 year- old male is referred for chronic azotemia
PMH: unremarkable
GPE: BP120/60 , LE edema
Labs: U/A SG 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 29

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 < 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 = H2O
Urea Mol wt : 60
BUN Mol wt. : 28
Normal BUN mg/dl
After filtration › 50% is reabsorbed by the tubule
BUN level is related to: Renal function, protein intake, and liver function 31

15. Creatinine 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

17. Creatinine Normal serum level 1–2 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 40

18. BUN/Creatinine ratio 10:1
Normal
Chronic renal failure 41

19. 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

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: <1%
Urine Sediment: Hyaline casts
What is the cause of < 10: 1 ,BUN to creat ratio now?

22. BUN/Creatinine ratio ‹ 10:1
Decreased urea load
Low protein diet
Liver failure
Inhibition of creatinine secretion
Cimetidine
Trimethoprim
Probenecid
Increased removal: Dialysis 44

23. BUN/Creatinine ratio ‹ 10:1
Increased creatinine load
Ingestion of cooked meat
Rhabdomyolysis
Interference with creatinine measurement
Ketosis
Cefoxitin
Increased muscle mass
Anabolic steroids
Muscular development 46

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 ,”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) > <350
Urine sodium (mmol/l) < >40
Urine/plasma urea nitrogen > <3
Urine/Plasma Creatinine > <20
Fractional Excretion of Sodium<1% >1%
Sediment normal “dirty brown”

27. 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

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 52

30. GFR 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)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 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 55

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