1. Done by Dr. Ali Abdul-Razak
Nephrotic syndrome
Done by Dr. Ali Abdul-Razak

2. Normal urinary protein excretion is ≤100 mg/m²/day or ≤ 150 mg/day
Proteinuria
Normal urinary protein excretion is ≤100 mg/m²/day or
≤ 150 mg/day
Normal A/G ratio is 1
First –morning sample of urine protein/creatinine value of more than 2-3 mg/mg indicates nephrotic range proteinuria and correlates with results from 24-hour urine collection.

3. TSP= g g
Albumin
Globulin
2-3.5 g

4. The dipstick is reported as
Negative
Trace (10-20 mg/dL)
1+ (30 mg/dL)
2+ (100 mg/dL)
3+ (300 mg/dL)
4+ (  mg/dL).

5. Causes of proteinuria:
Transient proteinuria: fever, exercise, dehydration, cold exposure, congestive HF, seizure and stress.
Orthostatic(postural) proteinuria.

6. Glomerular disease: (previous causes of glomerular hematuria) plus diabetic nephropathy.
Tubular disease: here the proteinuria is less than 1g/day like in cystinosis, Wilsons disease, galactosemia, heavy metal poisoning, acute tubular necrosis, reflux nephropathy.

7. Nephrotic syndrome
It is primarily a pediatric disorder and it is 15 times more common in children than adults.
It is characterized by heavy proteinuria (more than 2g/day or> 40mg/m²/hr), hypoalbuminemia (less than 2.5g/dl), edema, and hyperlipidemia.

8. Mesangial proliferation 5%
Idiopathic NS 90%
Minimum change disease 85%
Mesangial proliferation 5%
Focal segmental glomerulosclerosis
10%

9. The remaining 10% have NS due to membranous nephropathy or membranoproliferative GN

10. Pathophysiology:
By light microscopy :In minimum change disease the glomeruli appear normal or show minimum increase in the mesangial cells and matrix.
By electron microscopy reveal effacement of epithelial cell foot processes.
The underlying abnormality in NS is an increase in the permeability of the glomerular capillary wall (due to loss of negative charges), which leads to massive proteinuria and hypoalbuminemia.

12. fusion of foot process of epithelial in EM

14. Pathophysiology Edema appears when albumin less than 2.5 g/dl
decreased oncotic pressure
transudation of fluid to interstitial space
decreases intravascular volume
increased reabsorption of salt and water via the renin-angiotensin-aldosterone system and ADH, respectively

15. Pathophysiology : Hyperlipidemia
elevated serum lipids (cholesterol and triglycerides) and lipoprotein levels via:
hypoalbuminemia generalized increase in hepatic protein synthesis(including lipoprotein)
reduced levels of lipoprotein lipase(loss in urine)
diminished lipid catabolism

16. Clinical features
It more common in male than female ratio is 2:1
It is most common in children 2-6 years of age
initial episode and subsequent relapses may follow an upper respiratory tract infection

17. Hypertension and gross hematuria are uncommon
1. Proteinuria
symptomatic
pitting edema
Usual initial feature
eyes, lower extremities - generalized - ascites, pleural effusion - weight gain with decreased urine output
fluid accumulates in dependent areas and may shift from face & back to abdomen, perineum, and legs as the day progresses
Hypertension and gross hematuria are uncommon

18. Edema in scrotum
and penis
Ascites and abdomen
distention

20. 2. Other Manifestations:
abdominal pain, anorexia, diarrhea
3. complications:
1. Infections: child with NS liable for infection for different reasons:
Urinary loss of immunoglobulin(IgG, IgA, Complement  and properdin factor B)
Defective cell mediated immunity
Immunosuppressive therapy (steroids & cytotoxic drugs)
Malnutrition
Edema act as a good culture media for bacteria

21. Spontaneous bacterial peritonitis is the most frequent type of infection (streptococcal pneumoniae, gram negative like E.coli)
Also sepsis, pneumonia, cellulitis and UTI.
s/s of infection may be minimal if on steroid therapy
all patients should receive a single injection of polyvalent pneumococcal vaccine while in remission
Influenza vaccine should be given on yearly basis.

22. 2. Arterial and Venous Thrombosis
due to an increase in:
certain coagulation factors I, Ⅱ,Ⅴ,Ⅶ,Ⅷ,Ⅹ
inhibitors of fibrinolysis
platelet aggregation
- (decreased antithrombin III)
Partial immobilization
hemoconcentration

23. 3. Others
deficiencies of coagulation factors IX, XI, & XII
reduced levels of vitamin D.
growth retardation, malnutrition
4. Electrolyte imbalance:
hyponatremia, hypokalemia, hypocalcaemia
5. ARF: pre-renal and renal( rare with minimal change NS)
6. Hypovolemic shock.

24. Diagnosis
1. Urinalysis:
proteinuria to 4+ ,urinary protein exceed
40mg/m²/hour in children
Microscopic hematuria in 20% of cases.
2. Serum albumin level less than 2.5g/dl (with reversed ratio of albumin/globulin).
3. Decreased calcium due to decreased albumin.

25. 4. Serum cholesterol and triglyceride are elevated.
5. Normal C3 level
6. Renal function usually normal
6. Renal biopsy is not required in most cases.°

26. Treatment 1. Edema 1. Moderate salt-free diet
chlorothiazide mg/kg/d po bid with KCl supplement or
spironolactone 3-5 mg/kg/d po qid
NB. Be careful of hypovolemia and shock

27. Treatment 2. Severe salt-free diet fluid restriction
elevate swollen scrotum with pillows
25% albumin 1 gm/kg/d IV followed by
lasix 1-2 mg/kg/d po qid or
metolazone mg/kg/d po bid

28. 60 mg/m2/d po single daily dose (max. dose of 80 mg/d),
2. Proteinuria
1. Prednisone
1. Initial Therapy
60 mg/m2/d po single daily dose (max. dose of 80 mg/d),
Or 1-2mg/kg/day
for 4-6 weeks or until urine is negative of albumin
response time:
50% of cases respond within 8 days
80% of cases respond within 1 month - (a majority respond within 2 weeks)

29. protein-free urine for 3 consecutive days
Treatment goals:
protein-free urine for 3 consecutive days
normalization of albumin (complete remission)
steroid-responsive:
95% of those with minimal-change
55% of those with mesangial proliferative
20% of those with focal sclerosis

30. After 6 weeks daily dose give:
2. 'Weaning' Therapy
After 6 weeks daily dose give:
40 mg/m2/d po single morning dose on alternate days
For at least 4 weeks
slowly tapered for 1-2mo
Relapse , is the recurrence of proteinuria+edema
3. Relapse therapy
60 mg/m2/d po tid until proteinuria resolves for 3 consecutive days then 40 mg/m2/d po alternate day for 4 weeks

31. Steroid dependent NS: relapse shortly after switching to or after terminating alternate-day therapy .
Steroid resistant NS: those patients who continue to have proteinuria after 8 weeks of steroid therapy (renal biopsy indicated)
Therapy of steroid dependent and resistant NS:
cyclophosphamide
2-3 mg/kg/d po d for 8-12 weeks
may be given with alternate day steroid therapy

32. Side effects of cyclophosphamide:
leukopenia (monitor WBC count weekly & if <5,000, discontinue cyclophosphamide)
disseminated varicella infection
hemorrhagic cystitis
alopecia
sterility

33. Other options: for complicated NS
High dose pulse methylprednisolone 30mg/kg bolus , first 6 doses given every other day followed by tapering regimen for up to 18 mo
Cyclosporine 3-6mg/kg/day bid
Angiotensin converting enzyme inhibitors may be helpful adjunct therapy to reduce proteinuria.

34. Prognosis
Majority with steroid-dependent variety will have repeated relapses until spontaneous resolution of the disease toward the end of the 2nd decade .
Steroid resistant NS most often caused by focal segmental glomerulosclerosis have a poorer prognosis end stage RF

35. Prognosis
poor prognostic factors :
hematuria
hypertension
hypocomplementemia
Age < 1year and > 7years
All these are indications for renal biopsy

36. Congenital nephrotic syndrome
It refers to infants who develop NS during the first 3mo of life
The most common cause is the Finnish type, AR disorder (Scandinavian descent)
Usually presented with massive proteinuria, large placenta and marked edema recurrent infections progressive RF death by the age of 5 years.

37. Congenital nephrotic syndrome
Steroids and immunosuppressives are of no value.
Final treatment bilateral nephrectomy, frequent dialysis and kidney transplant .
Antenatal diagnosis : increase α fetoprotein in amniotic fluid.

38. Congenital nephrotic syndrome
Other causes of congenital NS include
--Congenital infections like syphilis, toxoplasmosis, rubella and CMV.
--Treatment of the underlying infection may improve or resolve the nephrotic state.