Nephrotic syndrome is a condition characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia. It is caused by damage to the glomerular capillary wall that increases permeability and allows large molecules like albumin to pass into the urine. The main types are minimal change disease, focal segmental glomerulosclerosis, and membranous glomerulonephritis. Treatment involves managing edema, restricting protein intake, and potentially using steroids, immunosuppressants, or diuretics depending on the specific cause and severity. Complications can include infection, thrombosis, hyperlipidemia, and end-stage renal disease if left untreated.

1. NEPHROTIC SYNDROME
SINGI

2. OUTLINE
• I.DEFINITION
• II. Pathophysiology,and anatomy
• III. Presentation
• IV. Investigation
• V. Classification of nephrotic syndrome
• VI. Some terms!
• VII. Management using General measures!
• VII. Treatment Goal
• IX. Complication of NS
• X.REFERENCE

3. I.DEFINITION
• Nephrotic syndrome is a syndrome caused by alteration in the
glomerular capillary wall.
• It consists of heavy proteinuria, hypoalbuminemia and often
associated with edema and hyperlipidemia

4. II.Pathophysiology, and anatomy

5. Plasma is filtered through the glomerular
barrier
• Components of plasma cross the three layers of the glomerular barrier during
filtration
• Capillary endothelium (cells have openings, fenestrae, of 70-100 nm D)
• Basement membrane, heparin sulphate proteoglycans (net negative charge)
• Epithelium of Bowman’s Capsule ( Podocytes–filtration slits allow size <60kD)
• The ability of a molecule to cross the membrane depends on size, charge, and
shape
• Glomerular filtrate therefore contains all molecules not contained by the
glomerular barrier - it is NOT URINE YET!

6. Pathophysiology cont’’’
• Increased permeability of glomerular to large molecules, mostly
albumin lead to proteinuria
• Proteinuria causes fall in serum albumin, if liver fails to compensate
by synthesis, plasma albumin decline, leading to edema formation.
• Edema. May be due to retention of sodium induced by renal disease
(overfill hypothesis)
• or secondary Sodium retention: hypoalbuminemia, low oncotic
pressure, fluid move to interstitial space, renal hypo perfusion,
activation of renin angiotensin system (underfill hypothesis)

7. III. Presentation
Clinical presentation
• edema (periorbital, scrotal, labial region then anasarca), Morning:
periorbital, Day time: extremity edema
• tiredness, leukonychia
• Hypertension, acute renal failure,
• Allergy in 50% with MCNS
Labs
• Proteinuria > 3g/24hrs, spot urine ACR>300mg/mmol, or urine protein to
urine creat ratio >2g/g, dipstick hematuria&3+.4+ proteinuria
• Hypoalbuminia, serum albumin <25g/dl
• Microscopic hematuria
• Hyperlipidemia, total cholesterol often > 10 mmol
• Protein electrophoresis: if no albumin, PARAPROTEIN, multiple myeloma

8. IV. Other investigation
• Exclude infection: Midstream urine, microscopy, culture & sensitivity
• HIV
• ESR, CRP, Glucose
• FBC and coagulation studies
• U&Es, and eGFR
• HBV&HCV, and LFT to exclude liver pathology
• Chest X-Ray and renal ultrasound, Doppler
• Renal u/s
• Renal biopsy

9. V. Classification of nephrotic syndrome
• Nephrotic syndrome:
• idiopathic 90% : MCN, FSGS, MN
• or secondary: Infection(HIV, HBV&HCV, malaria, syphilis )
• Drug (Gold, interferon, heroin, lithium, NSAID)
• Malignancies (leukemia, lymphoma)
• miscellaneous (diabetes, SLE…)

10. Idiopathic nephrotic syndrome
A.Minimal change nephrotic syndrome:
• nephrotic syndrome without hematuria
• Consist of 95% of nephrotic syndrome in children and 25% in adults
• Renal biopsy shows normal appearance, EM: fusion of foot processes
• Normal renal function usually.
• Spontaneous remission, treat only if edema and proteinuria

11. • B. Focal segmental glomerulosclerosis (FSGS)
• Nephrotic syndrome with microscopic hematuria, often HTN&
worsening renal impairment.
• Primary FSGS: unknown cause. on biopsy renal scleroses are seen,
interstitial fibrosis and focal tubal atrophy are common, mesangial
hypercellularity may be present
• Secondary FSGS: Occur as a result of loss of functioning nephrons

12. • C. Membranous glomerulonephritis
• Asymptomatic proteinuria with or without renal impairment,
microscopic hematuria and hypertension, it usually affect adults,
mostly men.
• Can have spontaneous remission
• Treatment for those with renal impairment
• Men, old age, heavy proteinuria are main progression risks

13. VI.Some terms!

14. VII. Management using General measures!
1.Initial treatment: stop Na+ intake, thiazide diuretic
or Furosemide(40-120mg/day + amiloride 5mg/day
2.Protein intake should be reduced, high induce proteinuria
3.Albumin infusion: only in diuretic resistance, or oliguria/uremia
without damage to glomerular. In MCNS: Some people need albumin +
diuretic
4.Hypercoagulable state: prophylactic anti coagulant, if RVT permant
anti coagulant
5.infection: due to loss of immunoglobulin in urine, Early detection and
aggressive treatment no prophylaxis
6.Lipid abonormalities, if high cholesterol, give atorvastatin…
7.ACEI/AIIRA: Decrease proteinuria by ↓BP, Glomerular Filtr pressure

15. Treatment cont’’’
• MCNS
• Start prednisolone 1 mg/kg/day (Max 80mg/day) 4-6 weeks
• Once remission reduce prednisolone by 30% every 4 to 6 weeks and stop
steroids in at least 12 weeks
• Relapse may occur and is treated with prednisolone
• Frequent relapses: can be due to steroid dependence or steroid resistant
Nephrotic syndrome,
cyclophosphamide 7.5 to 15 mg/day for 8 to 12 weeks,
cyclosporine 3-5 mg/kg/day target blood level 80-150ng/ml 8-12 weeks
•

16. FSGS
•

17. • Overt NS/Progressing renal impairment: drop in eGFR >15% in 1 year or >
10% in 2 consecutive years.
• Prednisolone 0.5-2 mg/kg/day should be continue for 6 months before
diagnosing steroid resistance
• cyclosporine aiming 150-300ng/ml in blood may be used but relapse after
discontinuation
• Cyclophosphamide 1-1.5 mg/kg/day with 1mg/kg/day steroid for 3-6
months, followed by a maintenance of prednisolone and azathioprine may
decrease proteinuria and slow down progession.
• Despite treatment 50% progress to ESRD in 10 years.

18. MGN
• There is spontaneous remission in 40%, hold treatment for 6 months
• Only people with severe proteinuria and progressing renal
impairment should be treated
• A) prednisolone 1mg/kg/day alternating daily with cyclophosphamide
1.5 to 2.5 mg/kg/day for 6-12 months
• Or
• Chlorambicil 0.2mg/kg/day in months 2, 4, and 6 and prednisolone
0.4 mg/kg/day in months 1, 3, and 5

19. VIII. Treatment Goal
• BP: <130/80 OR <120/75 If proteinuria or diabetes
• proteinuria,<1g/24 hours

20. IX. Complication of NS
• Thromboembolism, DVT, or renal vein thrombosis can lead to PE
• INFECTION: cellulitis, pneumonia, bacterial peritonitis, viral infection
• Acute renal failure,
• Hyperlipidemia
• ESRD

21. X.REFERENCE
• Kumar & Clarks medical management and therapeutics 1rst Ed 2011
• Uptodate
• The nephrotic syndrome,Pediatrics in Review Vol.30 No.3 March 2009
• www.ncbi.nlm.nih.gov/Nephrotic syndrome in adults
• Kumar & Clark’s clinical medicine 8th Ed 2012

22. THANK YOU