DIAGNOSIS OF

NEPHROTIC SYNDROME
 Definition of the nephrotic
syndrome

The NS is a clinical state characterized by

Massive albuminuria and heavy
hypoalbuminemia, often associated with
edema, hypercholesterolemia, and
generalized hyperlipidemia
Changes in Nephrotic
Syndrome
Glomerular membrane

- Normally impermeable to large proteins

- Becomes permeable to proteins, especially
albumin
- Albumin lost in urine (hyperalbuminuria)
- Serum albumin decreased (hypoalbuminemia)
- Fluid shifts from plasma to interstitial spaces
-Hypovolemia
-Ascites
Epidemiolog
y
Clinical classification of the NS
1. Primary NS : 90% of childhood cases
Minimal Change NS (MCNS)  70-80%
Focal Segmental Glomerulosclerosis (FSGS)
Mesangiocapillary Glomerulonephritis
Membranous Nephropathy

2. Secondary NS :
as a part of a systemic disease
or related to a drug or other toxin
Clinical classification of the NS
1. Congenital, the Finnish type of NS
Placenta enlargement
Massive edema
Genetic mutation on chromosome 19
2. Steroid sensitive NS
Steroid responsive : largely of children
with MCNS
3. Steroid resistant
Steroid nonresponsive : other glomerular
diseases (FSGS)
 NS
- ISKDC

Histology Patients Prevalence Steroid

% Response %
Minimal change disease 363 83 93.1
Focal Global GS 8 1.7 75
Focal segmental GS 37 7.9 29.7
Diffuse Mesangial Hypercellularity 9 1.9 55.6
Proliferative and Sclerosing GN 12 2.5 25
Membranoproliferative GN 29 6.1 6.9
Membranous nephropathy 6 1.2 0
Chronic GN 3 0.6 0
Unclassified 4 0.8 75
Total 471 100 78.1
Diagnosis of the NS

1. Clinical diagnosis
Clinical features
Clinical laboratories

2. Histopathologic diagnosis
Light microscopic  structural changes
Immunofluorescence findings
Electron-microscopic findings
 Clinical diagnosis of NS
A child with nephrotic syndrome has these
signs:
1. high levels of protein in the urine, a
condition called proteinuria
2. low levels of protein in the blood
3. swelling resulting from buildup of salt and
water
4. less frequent urination
4. weight gain from excess water
Clinical diagnosis of the NS
clinical features
● Edema
Accumulates in gravity dependent tissues
Puffiness around eyes
Anasarca is frequently present

● Pathogenesis of edema
80% of oncotic pressure due to albumin
Below 2 gr/dL edema accumulates
Intravascular volume depletion
Renin-aldosterone activation
Clinical diagnosis of NS
clinical features
● Evidence against of the pathogenesis
Analbuminemia
Steroid induced diuresis
Increased intravascular volume
Low renin/aldosterone levels
Ascites
Pretibial edema
Genital edema
Clinical diagnosis of the NS
Laboratory Features
● Albumin

Hypoalbuminemia due to loss via the kidney

Urinary excretion
Proximal tubular cells catabolism

● Immunoglobulins
IgG levels reduced
IgM levels elevated
IgM-IgG-Switching

●
Clinical diagnosis of NS
Laboratory Features
● Hyperlipidemia - hypercholesterolemia

● Hypovolemia is present
Not all patients are hypovolemic
Hematocrite may be elevated
● Hyponatremia is common
● Plasma creatinine is generally normal
 Volume distribution in ❚*
nephrotic syndrome?
Hypovolemia is characteristic for the early phases of
MCNS
(Donckerwolcke 2001 [110 MCNCS]) (underfilled theory)

Hypervolemia is characteristic for secondary nephrotic

syndromes (overfilled theory)

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Clinical diagnosis of NS
Laboratory Features
● Increased synthesis of cholesterol, triglycerides
and lipoproteins

● Decreased catabolism of lipoproteins

Decreased activity of lipoprotein lipase
Decreased LDL receptor activity
Increased urinary loss of HDL
Lp(a) levels are elevated
Clinical diagnosis of NS
Laboratory Features
Proteinuria is the primary abrormality
- “Selective”- almost entirely
albuminuria
> 40 mg/m2/hr or > 50 mg/kg
BW/24hs
- Urine protein to creatinine ratio
Normal : < 0.2 (< 0.15 adolescents)
Mild to moderate : 0.2 to 1.0
Heavy or severe : > 1.0 (suspected NS)
Unusual to see tubular>proteinuria
2,5 (established NS)
Histopathologic diagnosis of the
NS

Norma
l

MCNS

❚Van den Berg, Weening, Clinical Science (2004) 107, 125–136

Light microscopy of the MCNS
Immunofluorescence
Microscopy
Electron Microscopy
Histopathologic diagnosis of the
NS
Histopathologic diagnosis of the
NS
Histopathologic diagnosis of the
NS
For clinical application

Clinical diagnosis of the NS is

generally
based on
1. Edema
2. Massive proteinuria
3. Heavy hypoabuminemia
4. Hypercholesterolemia
Thank you

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