This presentation will help to approach Tubular ,overflow , functional proteinuria

1. Estimation of Proteinuria
By
Dr Sajid Lashari

2. 54 year old male resident of Hyderabad having blood
pressure 110/70 came to pre transplant OPD as a
donor for her sister
initial work up done.
Having 180 mg of 24 hour urinary protein.
24hour creatinine clearance is 85mL/min

3. Should we proceed him as a donor ?

4. History

5. Introduction
 The definition KDIGO increasingly used is that physiological
protienuira that do not exceed 150 mg per day and 140 mg per day
for children (Normal values vary by age)
 The magnitude of proteinuria and its composition in urine depend
on mechanism of renal injury that lead to protein losses.
Cont…

6.  Total protein: <150mg/day
 Albumin :<30mg/day
 Child: < 100mg/m2/day or 4mg/m2/hr
 Neonates: up to 300mg/m2/day (reduced reabsorption of filtered
proteins
Introduction

7. Composition of Normal Urinary Proteins
< 150mg/day

8.  Nephrotic range proteinuria (heavy proteinuria) is defined as
>3.5g/24hour or >40 mg/m2 per hour.
 Non Nephrotic Proteinuria : protein excretion of less than
3.5 gm per day.

12. Orthostatic Protienuria
 Orthostatic proteinuria is characterized by increased protein
excretion in the upright position but normal protein excretion when
patient is supine .
 Total protein excretion is generally less then 1g/day in orthostatic
protienuria but may exceed 3.5g/day in selected patients.

13. Transient proteinuria
 Transient proteinuria is diagnosed if repeat qualitative test is no
longer positive for proteinuria
 These patient need no further evaluation .
 Transient proteinuria can occur with fever and exercise perhaps
mediated by angiotensin 2 or norepinephrine-induced alterationin
glomerular permeability
 Proteinuria in such patient less then 1 g/day

15. Isolated proteinuria
 IP is defined as proteinuria without abnormalities in the urinary
sediment including hematuria or a reduction in Gfr as well as
absence of hypertension and diabetes

16. Mixed proteinuria
 In mixed type of proteinuria both albumin and small molecular
weight proteins such as alpha 1 microglobulin and beta 2
microglobulins are present.

17. Tubular Proteinuria
Tubular Proteinuria results from increase excretion of LMW
proteins such as beta 2 microglobulin , alpha 1 microglobulin,
retinol binding proteins
These molecules are normally filtered across the glomerulus
and then largely reabsorbed in the proximal tubules .
Variety of tubulointerstitial disease such as proximal renal
tubular acidosis with bicarbonate wasting and fanconi’s
syndrome can lead increased excretion of these smaller protein
.

18. When to suggest tubular proteinuria
 TP are found in hereditary and acquired tubular disorders.
 Hereditary causes TP include RTA , Cystinosis ,Wilson disease ,
Dent diease , nephronophthisis
 Acquired disorder include Nephrotoxic drugs , intersitial nephritis
ATN , Heavy metal poisoning

20. cont
 The measurement of B2 microglobulin is a sensitive assay for
proximal tubular injury
 The ratio of urine albumin to B2 microglobulin is less then 15 in
tubular proteinuria
 Whereas in glomerular proteinuria the ratio is greater then 1000.

23. Overflow Proteinuria
• Excessive production of an abnormal filterable plasma
protein(monoclonal gammapathies) that exceeds the tubular
capacity for reabsorption.
> Usually less than nephrotic range
 Examples: Multiple myeloma(Bence Jones protein),Myoglobinuria
in rhabdomyolysis and hemoglobinuria in hemolysis.

24. Measurement of Urinary Protein
 Qualitative
 Urine dipstick
 Sulfosalicylic acid test
 Heat coagulation test
 Quantitative
24-hour urinary protein
 Spot urinary Albumin/creatinine
ratio(ACR)

26. > Urine dipstick
Primarily detect albuminuria
less sensitive for other forms of
PROTIENUREA (low molecular
weight proteins, Bence Jones protein,
gamma globulins
Measurement of Urinary Protein

27. Urine dipstick
Measures albumin concentration via a colorimetric reaction between albumin
and tetrabromophenol blue producing different shades of green according to
the concentration of albumin in the sample.
 Negative
 Trace — between 15 and 30 mg/dL
 1+ — between 30 and 100mg/dL
 2+ — between 100 and 300 mg/dL
 3+ — between 300 and 1000 mg/dL
 4+ — >1000 mg/dL
Measurement of Urinary Protein

28. Pitfalls of Dipstick method
False positive
 Very Alkaline sample pH >7.0
 Contaminated by antiseptic agents
 Chlorhexidine or Benzalkonium
 Iodinated radiocontrast agents.
 Gross hematuria
False Negative
 Dilute urine (specific gravity <1.005)
 In which the predominant urinary protein is not
 Albumin

31. for Urinary protein Estimation following method are
used
.sulfosalicylic acid test SSA
.SSA Na sulphate
.Tricholoro acetic acid
.Benzethonium chloride
. Protein Dye binding method.

33. Our setup for Spot creatinine
( uncompensated Jaff method)
And for spot and 24 hour protein
Tricholoro acetic acid TCA

34. Instructions for 24 hour urinary collection
.Collect every drop of urine during day and
night.
Begin the urine collection in the morning.
Empty the bladder first time flush it down the
toilet.
Note exact time
Finish by collecting the first urine passed by
next morning.
This should be within ten minutes before or
after
First time of the morning void of first day..

35. Instructions for split Urine collection
Daytime collection.
.After the first morning void discarded then all
subsequent void collected through out the day .
In the evening lie down for 2 hours just before going to
sleep go to washroom last time and add this urine in
daytime jug.

36. Nighttime collection
Any urine voided over the night and also first
morning void collected in nighttime jug ..

37. Limitations of 24 hour urine collection
 The gold standard for measurement of protein excretion is 24 hrs
urine collection.
 Major limitation are , it is cumbersome for patient. It is often
collected incorrectly( over and under collections are common) .

38. Limitations of UPCR , UACR
 The UPCR and UACR are heavily influenced by urine
protein creatinine concentration.
 Urinary protein excretion can vary throughout the day i.e by
exercise and posture.
 In addition the accuracy of ratio is diminished if creatinine
excretion is markedly high ( Large muscle mass ) or lower
than average population (small muscle mass) will
underestimate and overestimate proteinuria .

39. Data From: GINSBERG JM CHANG BS N
Engl J MED

42. Thanks

44. THANKS