1. NEPHROTIC SYNDROME
Ayça Vitrinel, MD

2. Nephrotic syndrome (NS)
NS is characterized by
Proteinuria
40 mg/m2/hr in children
3.5 gr/24 hr in adults
Hypoalbuminemia
<2.5 gr/dl
Edema
Hyperlipidemia

3. Etiology Idiopathic NS (90%) Membranous nephropathy
Minimal change (85%)
Mesangial proliferation (5%)
Focal sclerosis (10%)
Membranous nephropathy
Membranoproliferative GN
(10%)

4. The nephrotic syndrome consists of
proteinuria,
hypoalbuminemia,
edema,
hyperlipidemia.
Of these, the proteinuria is primary, with the development of hypoalbuminemia, edema, and hyperlipidemia as secondary findings.

5. Pathophysiology(1) Proteinuria
Increase in glomerular capillary wall permeability
The mechanism of this increase is unknown
T cell dysfunction leads to alteration of cytokines
Loss of negatively charged glycoproteins within the capillary wall
Focal segmental glomerulosclerosis is characterized by a plasma factor
Perhaps produced by lymphocytes
Increases glomerular permeability to proteins

6. Pathophysiology(2) Edema
Appears when the serum albumin level falls below 2.5 g/dl
Inıtıated by the development of hypoalbuminemia (result of urinary protein loss)
Decrease in the plasma oncotic pressure
Permits transudation of fluid from the intravascular compartment to the interstitial space
The reduction of intravascular volume
Decreases renal perfusion pressure
Activating renin-Agt-aldosteron system
Stimulates distal tubular reabsorbtion of Na

7. Pathophysiology(3) The reduced intravascular volume
stimulates the release of ADH
Enhances the reabsorbtion of water in the collecting duct
The reabsorbed Na and water are lost into the interstitial space exacerbating the edema

8. Pathophysiology(4) Hyperlipidemia
Cholesterol, triglycerides and lipoprotein levels are elevated
Hypoproteinemia
stimulates generalized protein synthesis in the liver, including the lipoproteins
Lipid catabolism is diminished
owing to reduced plasma levels of lipoprotein lipase, the major enzyme system that removes lipids from the plasma

9. Idiopathic Nephrotic syndrome
Minimal change disease
Mesangial proliferation
Focal segmental glomerulosclerosis
The cause remains unknown
The disease is mediated by immunologic mechanisms-abnormal T-lymphocyte function

10. Pathology (1) Occurs in three morphologic patterns
Minimal change disease
The glomeruli appear normal or show a minimal increase in mesangial cells and matrix
Electron microscopy reveals retraction of the epithelial cell foot processes
More than 95% of children respond to corticosteroid therapy

11. Pathology (2) Mesangial proliferative group Focal sclerosis
Diffuse increase in mesangial cells and matrix
50-60% patients respond to CST therapy
Focal sclerosis
The majority of glomeruli appear normal or show mesangial proliferation, others show segmental scarring in one or more lobules
Frequently progressive
Lead to end-stage renal failure
May recur in a transplanted kidney

12. Clinical manifestations (1)
More common in boys than girls (2:1)
Most commonly appears between the ages of 2-6 years
May follow an apparent viral URTI, reactions to insect bites, bee stings or poison ivy

13. Clinical manifestations (2)
Edema around the eyes and in the lower extremities
Edema becomes generalized
Weight gain, development of ascites or pleural effusions, declining urine output
Anorexia, abdominal pain, diarrhea, hypertension is common

14. Diagnosis (1) Urinalysis reveals +3 or +4 proteinuria
Microscopic hematuria may be present (20%)
Spot urine protein/creatinine ratio exceeds 2.0
Renal function may be normal or reduced
Serum cholesterol or triglyceride levels are elevated

15. Diagnosis (2) Serum albumin level is generally less than 2 g/dl
Total serum calcium level is diminished
C3 level is normal
Children with onset of NS between the ages of 1 and 8 years are likely to have steroid responsive minimal change disease
no biopsy is indicated

16. Complications(1) Infections Decreased Ig levels
Edema fluid acting as a culture medium
Protein deficiency
Decreased bactericidal activity of leukocytes
Immunosuppressive therapy
Decreased perfusion of spleen due to hypovolemia
Loss in the urine of a complement factor that opsonizes certain bacteria

17. Complications(2) Infections S.pneumoniae is the most common organism
Peritonitis
Sepsis
Pneumonia
Cellulitis
Urinary tract infection
S.pneumoniae is the most common organism
E.coli may be encountered

18. Complications(3) Arterial and venous thrombosis
Increased prothrombotic factors
Fibrinogen, thrombocytosis, hemoconcentration, relative immobilization
Decreased fibrinolytic factors
Urinary losses of ATIII, protein C and S

19. Treatment
Edema
Na intake reduced
Steroids

20. Prognosis
Most children with steroid responsive nephrosis have repeated relapses until the disease resolves spontaneously toward the end of the 2nd decade

21. Secondary NS(1) Glomerulonephritis
NS may develop during the course of any type of GN but is most common in association with:
Membranous age>8
Membranoproliferative hypertension
Poststreptococcal hematuria
LE renal dysfunction
Malaria extrarenal symptoms
HSS

22. Secondary NS(2)
Tumors
NS may be associated with several extrarenal neoplasms
Carsinomas, lymphomas
Tm produces a lymphokine that increases glomerular capillary wall permeability

23. Secondary NS(3) Drugs Penicilamine probenecid phenytoin
Captopril ethosuximid gold
Metimazole NSAID lithium
Mercury comp. procainamide
chlorpropamide

24. Secondary NS(4)
Infections
Hepatitis B
Hepatitis C
Leprosy
HIV

25. Congenital NS Infants develop NS within the first 3 months of life
Finnish type (autosomal recessive)
Gene has been located to the long arm of chromosome 19
Antenatal diagnosis is possible