Nephrotic Syndrome

Question 1

is characterised by

Answer 1

It  is characterised by 
Heavy proteinuria (>3.5 g/24 hr in adults or >40 mg/m2/hr in children), 
Hypoalbuminemia (<2.5 g/dL), 
Edema
Hyperlipidemia.

Question 2

Etiology

Answer 2

(90%) of nephrotic syndrome in children is a form of the
idiopathic nephrotic syndrome (INS)
while (10%) is secondary .

Question 3

Idiopathic nephrotic syndrome

3 types

Answer 3

Minimal change disease (85%)
 Mesangial proliferation (5%), 
 Focal segmental glomerulosclerosis (10%).

Question 4

The secondary cases are related to other GN

Answer 4

Membranoproliferative GN (MPGN)

• Membranous nephropathy
• other systemic diseases
• drugs
• infections

Question 5

Causes of Proteinuria

Answer 5

TRANSIENT PROTEINURIA
ORTHOSTATIC (POSTURAL) PROTEINURIA
TUBULAR DISEASES
GLOMERULAR DISEASES

Question 6

TRANSIENT PROTEINURIA causes

Answer 6

FeverExerciseDehydrationCold exposureCongestive heart failureSeizureStress

Question 7

False-positive proteinuria

Answer 7

may be seen in patients with gross hematuria,
contamination with antiseptic agents (chlorhexidine and benzalkonium chloride),
urinary pH greater than 7.0
UTI

Question 8

False-negative proteinuria

Answer 8

occur with dilute urine or when the predominant urinary protein is not albumin

Question 9

a Upr/Ucr ratio normal and abnormal value

Answer 9

Normal < 20mg/mmol

Nephrotic range > 200mg/mmol

Question 10

Pathophysiology of edema

Answer 10

An increase in permeability of the glomerular capillary wall, which leads to massive proteinuria and hypoalbuminemia
Hypoalbuminemia causes a decrease in the plasma oncotic pressure ,and fluid transudation from the intravascular compartment to the interstitial space…leads to edema

Question 11

Pathophysiology of elevated lipid levels

Answer 11

Hypoalbuminemia stimulates generalized hepatic protein synthesis, including synthesis of lipoproteins.
Lipid catabolism is diminished

Question 12

pathophysiology of proteinuria

Answer 12

injury to the podocytes
as with Various forms of INS associated with mutations in podocyte genes, with the slit-diaphragm and podocyte cytoskeleton proetiens (nephrin and podocin

Question 13

MCD clinical picture

Answer 13

100% nephrotic
10-20% hematuria
10% hypertension
Doesn’t progress to end stage renal failure
90% response to steroids
It is more common in males than in females (2:1)
Frequency 75% in children, 15% in adults
appears between the ages of 2 - 6 yr
Present with edema, which is initially noted around the eyes and in the lower extremities
edema may become generalized, with the development of ascites, pleural effusions, and genital edema .
hypertension and gross hematuria are uncommon

Question 14

Differential diagnosis:

for MCD

Answer 14

protein-losing enteropathy,
hepatic failure,
congestive heart failure,
Other chronic glomerulonephritis, and protein malnutrition

Question 15

investigation for MCD

Answer 15

• Urine R&M .. For protein and RBC
• 24h urine collection or Upr/ucr ratio
• Urine culture
• Serum albumin
• KFT
• CBC
• C3 and C4 level
• HBV and HCV serology
• ANA , DS-DNA and AsO titre if needed

Question 16

when renal biopsy is needed in MCD

Answer 16

Atypical presentation:
hematuria ( gross )
hypertension,
renal insufficiency, hypocomplementemia
age < 1yr or > 12yr
Response to steroid ttt (SDNS, SRNS, FRNS )

Question 17

Diagnosis MCD

Answer 17

Urinary protein excretion in the nephrotic range (exceeds 40 mg/m2/hr) in children
microscopic hematuria may be present in 20% of children
serum albumin is < 2.5 g/dL,
Serum creatinine value is usually normal
increased serum cholesterol and triglyceride
C3 and C4 levels are normal.
Renal biopsy is not required for diagnosis in most children with Idiopathic nephrotic syndrome ..(MCD)
Minimal change disease (85%):
light microscopy glomeruli appear normal or show a minimal increase in mesangial cells and matrix.
Immunofluorescence : are negative,
Electron microscopy simply reveals effacement of the epithelial cell foot processes.

Question 18

Focal segmental glomerulosclerosis in pathology lab

Answer 18

glomeruli show mesangial proliferation and segmental scarring on light microscopy .
immunofluorescence microscopy shows IgM and C3 staining.
Electron microscopy shows segmental scarring of the glomerular tuft with obliteration of the glomerular capillary lumen

Question 19

Mesangial proliferation

in pathology lab

Answer 19

diffuse increase in mesangial cells and matrix on light microscopy.
Immunofluorescence microscopy shows mesangial IgM and/or IgA staining.
Electron microscopy reveals increased numbers of mesangial cells and matrix as well as effacement of the epithelial cell foot processes.

Question 20

Treatment of MCD

Answer 20

Intravenous administration of 25% Albumin

• Steroids
• other medications eg(cyclophosphamide, cyclosporin

Question 21

Complications

Answer 21

Drug Side Effects:
Steroids : (cushingoid appearance, hypertension, cataracts, and/or growth failure)
Cyclophosphamide (neutropenia, disseminated varicella, hemorrhagic cystitis, alopecia, sterility
Ciclosporin ( hypertension, nephrotoxicity, hirsutism, and gingival hyperplasia, neutropenia
Infections
Spontaneous bacterial peritonitis is the most frequent type of infection
Thrombosis

Question 22

why Infection is the major complication of nephrotic syndrome

Answer 22

Increased susceptibility to bacterial infections owing to urinary losses of immunoglobulins and properdin factor B, defective T cell-mediated immunity, immunosuppressive therapy, malnutrition, edema……

Question 23

most common organism causing peritonitis

Answer 23

Streptococcus pneumoniae is the most common organism causing peritonitis, gram-negative bacteria such as Escherichia coli may also cause it