2. Introduction
Normal urinary protein excretion is
approximately 150mg/day.
Normal rate of protein excretion in urine is
variable in younger children:
<4 mg/m2/hour or <100 mg/m2/day
Neonates is higher up to 300 mg/m2
(reduced reabsorption of filtered protein)
3.
4. Protein handling by the kidneys
in normal children
The low excretion rate of protein
occurs because:
1- the glomeruli restrict filtration of
large serum protein, and
2- the proximal tubules reabsorb
most of the LMW proteins
5. The glomerular capillary barrier is a
complex and selective filtration barrier
that is made of three layers:
-Endothelium with fenestration
-Glomerular basement membrane
-The epithelial cells and the complex
network of podocytes
6.
7. Despite the complex structural
attributes of each component, it
functions as a single filtration unit.
The glomerular filtrate reaching the
proximal tubule contains mostly filtered
LMW protein and minor amounts of
albumin…..
8. ….and approximately 40-50% of this
protein consists of Tamm-Horsfall
protein, a glycoprotein secreted by the
ascending limb of the loop of Henle.
9. Composition of protein normally found in the
urine:
T-H 40%
Albumin 40%
IgG 10%
Light chains 5%
IgA 3%
10. CASE 1
At a well child visit a 23 month old has a
measured urinary protein of 30 mg/dl
(+1 on dipstick) and a urine creatinine of
180 mg/dl. Is this child passing more
protein in the urine than normal?
11. Case 1: Answer
No, this boy is not passing abnormal amounts
of protein.
U prot/Cr ration is less than 0.5 (mg
protein/mg creatinine).
Repeat evaluation in a few week to a month.
12. Protein handling by the kidneys in
children with renal disorders
Occurrence of proteinuria in a single urine
is relatively common.
The prevalence is generally between 5% to
15% of normal children in a random urine
specimen.
Less than 1% of children with random
protein will have persistent proteinuria on 4
successive specimens
13. Proteinuria is a marker of renal disease.
The dilemma for the PCP is to
differentiate the child with transient or
any other benign forms of proteinuria
from children with renal disease.
14. Abnormal protein excretion
Urinary protein excretion in excess
of 100 mg/m2/day or 4mg/m2/hr
Nephrotic range proteinuria is
defined as >1000 mg/m2/day or
40mg/m2/hr
15. Three main mechanism:
Glomerular (increase filtration)
Tubular (decrease reabsorption)
Overflow (marked overproduction
of a particular protein)
16. How do we measure urinary protein?
Quantitative methods
Urine dipstick
negative
trace between 15-30mg/dl
1+ 30-100 mg/dl
2+ 100-300mg/dl
3+ 300-1000mg/dl
4+ >1000mg/dl
17.
18. Qualitative assessment
May be necessary to differentiate
glomerular from tubular protein
(Urine protein electrophoresis)
19. Case 2
A child aged 5 years visit your office. She has
a fever of 103o F. A viral upper respiratory
infection is diagnosed. On urine dipstick she
has 1-2+ proteinuria.
What follow up does this child require for her
proteinuria?
20. Case 2: Answer
Repeat urinalysis after acute illness has
resolved
When asking patient to present for urinalysis,
instruct them not to exercise prior to giving
sample.
21. Approach to the child with proteinuria:
-Transient or Intermittent
Associated with fever, stress,
dehydration or exercise.
-Orthostatic
Elevated protein excretion when
subject is upright and normal when
recumbent or…..
23. Case 3
A 13 year-old adolescent was found to
have proteinuria on a routine sports
physical examination. His blood pressure
was normal and he had no edema. His
weight was 40 Kg. How would you set
about and initial evaluation of his
proteinuria?
24. Case 3: Answer
Ask patient to bring in first morning
sample to the office.
Patient should urinate immediately after
getting out of bed.
If proteinuria is confirmed on first
morning sample, then quantify with 24 hour
urine collection.
25. Timing of urine testing
Dipstick
First morning urine (neg or trace)
Ambulatory urine (1-3+)
Timed ambulatory and recumbent urine collections
Ambulatory (14 hr) 325 mg protein
560 mg creatinine (0.6)
Recumbent (10 hr) 30 mg protein
480 mg creatinine (0.06)
26. Association between proteinuria
and progressive renal damage
Increasing levels of proteinuria provide
the best predictor of progressive renal
damage.
Persistent proteinuria should be viewed
as marker of renal disease, and also as a
cause of progressive renal injury.
27.
28. Association between proteinuria and
cardiovascular disease
Severe persistent proteinuria may also be a
long term risk factor for atherosclerosis in
children.
As the severity of proteinuria increases it is
associated with variety of metabolic
disturbances that contribute to cardiovascular
disease, e.g., hypercholesterolemia,
hypertriglyceridemia, and hypercoagulability.
29. Evaluating children with proteinuria
History and physical
Thorough history and physical
-change in urine volume or color
-edema
-increase BP
-recent strep infection
-family history for renal disease and
hearing loss (Alport syndrome)
30.
31.
32.
33. The Need for Renal Biopsy
The key indication for biopsy in any
renal disorder are the need to make
specific diagnosis for therapeutic
reasons or to provide a prognosis.
34. Nonspecific treatment options for
persistent proteinuria
Dietary recommendations.
It is recommended that children with
proteinuria receive the recommended daily
allowance of protein for age.
Blood pressure Control/Inhibition of
Angiotensin effects
Renal function is better preserved when lower
systolic blood pressures are achieved.
35.
36. Neprotic Syndrome
Nephrotic syndrome is characterized by
massive proteinuria, hypoalbuminemia,
edema, and hyperlipidemia; the most
common presenting symptom is edema.
37. Introduction
The annual incidence of Nephrotic
syndrome in healthy children is 2 to 3
new case per 100,000 children younger
than 18 years of age.
The peak age lf onset is at 2 to 3 years.
38. Definition
The diagnosis of NS is the presence of
urinary protein, with the albumin
disproportionately greater than globulin.
39. Clinical Diagnostic Criteria
1- Generalized edema
2- Hypoproteinemia <2 g/dL
(disproportionately low albumin in
relation to globulin)
40. 3-Urine protein to urine creatinine ratio
in excess of 2 (first A.M. void) or a
24- hour urine that exceeds
50mg/Kg body weight
4-Hypercholesterolemia (>200 mg/dL)
41.
42.
43. The mechanisms for edema include:
-Transudation of fluid from the
intravascular space into the intestitium
secondary to decreased albumin and
- Increased renal tubular
reabsorption of sodium and water
44.
45. The hyperlipidemia is secondary to:
-Increase in lipoprotein synthesis by
the liver and
-Decrease in lipid catabolism
resulting from reduced activity of the
enzyme lipoprotein lipase and lecithin
cholesterol acetyltransferase.
46. Case 4
An 8 year old boy presented with ankle swelling and
was found to have hypertension, hematuria and 4+
proteinuria. The remainder of the systematic
examination was normal.
A 24 hour urine collection contained 10 grams of
protein, and his serum albumin was 2.0 g/dl.
The creatinine clearance was normal for his age.
Streptococcal tests and serum complement 3 level
were normal. He received an 8 week course of
glucocorticoids without response.
What are the next appropriate diagnostic and
therapeutic steps?
47. Case 4: Answer
Steroid resistant nephrotic
syndrome
Renal biopsy performed
Diagnosis: Focal segmental
glomerulosclerosis (FSGS)
55. Complications
One true complication of NS is the
tendency to developed infections.
IgG antibody is lost in the urine, and
complement activation is impaired by
concomitant loss of factor B.
56. Marked intravascular depletion causes
diminished splachnic blood flow and
hypoxia, and a marked tendency to
thrombosis cause microinfarction,
lowering resistance of the bowel wall to
bacteria passage.
57. Peritonitis is a major contributor to
the 1% to 2% mortality in NS
The second major contributor is
Thromboembolism, however
anticoagulant therapy is not justified
during remission.
58. Growth is often impaired in NS
There may be losses of IGF-binding
protein, which could account for the
depressed serum concentration of IGF-
I and IGF-II.
59.
60. Prognosis
Mortality in minimal-change NS is
approximately 2%
Of the remaining 98%, most are steroid-
responsive
about 2/3 experience 1/3 possible
single relapse developing
protracted series of
relapses