- Proteinuria refers to abnormal levels of protein in the urine and can be caused by damage to the glomerular filtration barrier in the kidneys. The glomerular filtration barrier is normally highly selective and prevents protein leakage into the urine. - Proteinuria is classified as transient, orthostatic, asymptomatic, symptomatic, isolated or associated with other symptoms. Measurement involves urine dipstick testing, 24-hour urine protein estimation, or urine protein-creatinine ratio. - Evaluation of proteinuria includes assessing for signs and symptoms, measuring extent of proteinuria, and considering underlying causes like glomerular disease, tubular dysfunction, or overflow proteinuria from other medical conditions. Treatment is directed at the underlying cause

1. Approach To Proteinuria
Dr.Jishnu.K.R
PGT- Pediatrics
Moderator-Dr.Chinmay Behera
Associate Professor
Department Of Pediatrics

2. History
Hippocrates (400 B.C.) described bubbles on the surface of
the urine could be due to renal disease.
Dr.Richard Bright first described the association between
proteinuria and renal disease in the 1800.

3. Glomerular Filtration Barrier

5. Components
• 3 components of Glomerular Filtration Barrier
 Endothelial cell(Fenestrated 70-100nm)
 Basement membrane
 Podocyte(Visceral epithelial cell)

6. • Glomerular filtration system is extraordinarily permeable to water
and small solutes
• Almost completely impermeable to molecules of the size and
molecular charge of albumin (a 70,000-kDa protein)
• This selective permeability, called glomerular barrier function,
discriminates among protein molecules according to their :-
 size (the larger, the less permeable)
 charge (the more cationic, the more permeable)
 configuration.

7. • Charge barrier :-
 Acidic proteoglycans(Heparan sulfate) of the GBM
 Sialoglycoproteins of epithelial and endothelial cell coats.
• Size barrier is accounted by slit diphragm made up of podocytes of
visceral epithelium.

8. Normal Protein Excretion
• Normally excreted proteins:-
 15% Albumin
 50% Tamm-Horsfall Protein
 35% Beta-2 microglobulin,retinol binding protein and N-Acetyl-D-
Glucosaminidase.
Indian Journal Of Pediatrics
May 2012

9. Normal Protein Excretion
• Normal protein excretion
 Child: < 100mg/m2/day or 4mg/m2/hr(Tamm Horsfall,
IgA,Haptoglobin, Transferrin, β2 microglobulin)
 Neonates: up to 300mg/m2/day

10. Abnormal Protein Excretion
• Urinary protein excretion in excess of 100 mg/m2 per day or 4 mg/m2
per hour in children
• In neonates normal urinary protein excretion is as high as
300mg/m2/day
• Nephrotic range proteinuria (heavy proteinuria) is defined as
>3.5g/24hour or >40 mg/m2 per hour or urine protein creatinine ratio
>2.

11. Epidemiology
• Prevalence of isolated proteinuria detected by routine analysis in
school children is approximately 6.3%.
• Majority of the school children had transient or orthostatic
proteinuria.
• Prevalence increased with increasing age and showed peak in
adolescence.
Indian Journal Of Pediatrics
May 2012

12. Classification
• Asymptomatic/Symptomatic
• Transient/Persistent
• Isolated/Associated with systemic symptoms

13. Mechanism of Protein Handling by Kidney
• Glomerular permeability
 Charge and size selective properties of the glomerular capillary wall
prevent significant amounts of proteins from entering the urinary
space.
 Low Molecular Weight protein cross the capillary wall but are
reabsorbed by the proximal tubule.
 Small amount of protein that normally appears in the urine is the
result of normal tubular secretion.

14. Pathophysiology Of Proteinuria
• 3 possible mechanisms:-
1. Glomerular proteinuria:-
disruption of the glomerular capillary wall
2. Tubular proteinuria:-
tubular injury or dysfunction that leads to ineffective reabsorption of
mostly low-molecular-weight proteins
3. Increased production of plasma proteins(Overflow Proteinuria) :-
multiple myeloma, rhabdomyolysis, or hemolysis

15. Glomerular Proteinuria
• Results from alterations in the permeability of any of the layers of
the glomerular capillary wall to normally filtered proteins.
• Range widely from <1 g to >30 g of protein in a 24 hr period.
• The podocyte is the predominant cell of injury in most glomerular
diseases characterized by heavy proteinuria
Nelson Textbook Of Pediatrics

16. • Suspected in any patient with a first morning urine
 Protein: creatinine ratio >1.0
 Accompanied by hypertension, hematuria, edema, or renal
dysfunction

17. Tubular Proteinuria
• Tubulointerstitial compartment of the kidney can cause low-grade
fixed proteinuria (protein: creatinine ratio 0.2 : 1.0).
• Injury to the proximal tubules can result in diminished reabsorptive
capacity and the loss of these low-molecular-weight proteins in the
urine.
• In occult cases, glomerular and tubular proteinuria can be
distinguished by electrophoresis of the urine.
• In tubular proteinuria, little or no albumin is detected, whereas in
glomerular proteinuria, the major protein is albumin

19. Microalbuminuria
• Presence of albumin in the urine above the normal level but below
the detectable range of conventional urine dipstick methods(30-
300mg/24hour).
• The mean level of urinary albumin excretion falls between 8 and 10
mg/g of creatinine in children >6 yr of age.
• Found to be associated with obesity and to predict, with reasonable
specificity, the development of diabetic nephropathy in type 1
diabetes mellitus.

20. Transient Proteinuria
• 10% of children who undergo random urinalysis have proteinuria by
a single dipstick measurement.
• Cause remains elusive(hemodynamic change in the glomerular
blood flow)
• Contributing factors:-
 Temperature >38.3°C (101°F)
 Exercise
 Dehydration,
 Cold exposure
 Heart failure
 Seizures
 Stress.
 usually does not exceed 1-2+ on the dipstick.
• No evaluation or therapy is needed for children with this benign
condition.

21. Orthostatic Proteinuria
• Most common cause of persistent proteinuria in school-age
children and adolescents, occurring in up to 60% of children with
persistent proteinuria.
• Excrete normal or minimally increased amounts of protein in the
supine position.
• In the upright position, urinary protein excretion may be increased
10-fold up to 1,000 mg/24 hr (1 g/24 hr).
• Only short term studies regarding prognosis have been published on
children and these indicate a good prognosis
• In one such study only 17 children out of 900 orthostatic proteinuria
children devoloped persistence of proteinuria.
Archives of Diseases in Childhood
March 2015

22. • The absence of proteinuria on the first morning urine sample for 3
consecutive days confirms the diagnosis of orthostatic proteinuria.
• Cause of orthostatic proteinuria is unknown, although altered renal
hemodynamics and partial left renal vein compression in the upright
position have been proposed as possible cause.

23. Signs & Symptoms
 oliguria,
 polyuria,
 weight loss,
 skin lesions,
 joint symptoms,
 recent infections,
 previous abnormal urine analysis,
 recent intake of medications like NSAIDS.
• Family history of hypertension,renal disease,autoimmune
disease,visual impairment.

24. Signs & Symptoms contd
• Edema
• Flank Pain
• Fluid overload
• Organomegaly
• Rashes
• Anemia
• Joint swellings
• Signs of osteodystrophy

25. Measurement Of Urine Protein

26. Urine Dipstick Testing
• 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 100 mg/dL
 2+ — between 100 and 300 mg/dL
 3+ — between 300 and 1000 mg/dL
 4+ — >1000 mg/dL

27. • False-positive results:-
 Very high urine pH (>7.0)
 Highly concentrated urine specimen
 Contamination of the urine with blood
• False-negative test results:-
 Dilute urine or a large volume of urine output
 Disease states in which the predominant urinary protein is not
albumin.
 Limitation:- Cannot detect other types of proteins such as plasma
proteins,globulins and low molecular weight proteins.

29. 24Hour Urine Protein Estimation
• Gold standand
• Urinary protein excretion in the normal child is less than 100
mg/m2/day or a total of 150 mg/day.
• In neonates, normal urinary protein excretion is higher, up to 300
mg/m2 because of reduced reabsorption of filtered proteins
• In children: levels 4 mg/m2 /hour is abnormal
• Proteinuria of greater than 40 mg/m2/hour is considered heavy or in
the nephrotic range

30. Urine Protein-Creatinine Ratio
• Should be ideally performed on a first morning voided urine
specimen to eliminate the possibility of orthostatic proteinuria.
• A ratio of <0.5 in children <2 yr of age and <0.2 in children >2 yr of
age suggests normal urinary protein excretion.
• A ratio greater than 2 suggests nephrotic-range proteinuria.

31. • Depends on the production and excretion of creatinine which can
vary for each child's body state.
• Urine Albumin-Creatinine Ratio:- Normal range is less than 20-30mg
of urine albumin per gram creatinine.

36. Approach
Indian Journal of Pediatrics
May 2012

37. Treatment
• Directed at the underlying cause
• Reassured if the proteinuria is transient or orthostatic,asymptomatic,
no hematuria, has normal blood pressure and glomerular filtration
rate
• A child with persistent proteinuria should initially receive a blood
pressure measurement, urinalysis and serum creatinine estimation
at least once in a year until the child is free of proteinuria
• Receive the recommended daily allowance of protein for age
• Combination ACEI and ARB therapies have additive antiproteinuric
activity

38. Thank You