Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia. It is caused by conditions that damage the glomerulus, increasing permeability to plasma proteins. Primary causes include minimal change disease, membranous glomerulonephritis, and focal segmental glomerulosclerosis. Secondary causes can be infections, connective tissue diseases, and cancers. Treatment focuses on reducing proteinuria with ACE inhibitors or NSAIDs, managing edema and hyperlipidemia, and treating the underlying condition, often with corticosteroids, cyclophosphamide, or cyclosporine.

1. Nephrotic Syndrome

2. Is secondary phenomena that occur when
substantial amts of protein are lost in the
urine
Characterised by
• Proteinuria >3.5g/24hrs(urine may be
frothy)
• Hypoalbuminaemia < 30g/L
• Oedema & Generalised fluid retention
• Hyperlipidaemia
• Intravascular volume depletion with
hypotension/expansion with HTN, may
occur

3. Pathogenesis
Excessive permeability of plasma proteins - >> heavy proteinuria
Depletion of plasma proteins , mainly albumin – hypoalbuminaemia
Liver compensates but not successful - >> reversed A:G ratio
Reduced albumin -> decreased colloid oncotic pressure of the
blood -> oedema
Increased Lipoprotein synthesis and decreased catabolism by liver
->> Hyperlipidaemia (mainly VLDL and /or LDL)
HDL is also lost in urine when heavy proteinuria occurs
Loss of body proteins (immunoglobulins /complement) -> frequent
infection
Loss of anticoagulants antithrombin III , antiplasmin - > thrombotic
and embolic phenomenon

4. Causes
PRIMARY
• Minimal change disease
• Membranous glomerulonephritis
• Mesangial proliferative glomerulonephritis
• Focal & segmental glomerulosclerosis
• Mesangiocapillary glomerulonephritis

5. Causes
Secondary
• Infection: Bacteria
endocarditis,Malaria,Syphilis,Hepatitis
B,HIV
• Connective tissue diseases:
SLE,Rheumatoid arthritis
• Neoplasms: Hodgkin’s
lymphoma,Carcinomas,Leukaemias
• Metabolic: DM,Amyloidsis
• Drugs & toxins: Captopril,gold,Mercury

6. The diseases the cause Nephrotic
syndrome all affect the glomerulus
Mechanism:
• injury to podocytes
• Changed architecture
Scarring
Deposition of matrix or other
elements

7. Clinical Presentations
fluid retention ->abdominal
distention,ascites,edema,puffy eyelids
,scrotal swelling,weight gain,shortness of
breath
Anorexia
Hypertension
Oliguria
Orthostatic hypertension
Foamy urine
Periorbital edema
Pitting edema of lower limbs

8. Investigations
1.Urine analysis:
Protein : creatinine ratio in a spot
sample of urine (PCR>100mg/mL -
substantial)
proteinuria > 3.5g/L
Estimate 24 hour albumin excretion
(ACR>70 mg/ml)
RBC casts and WBC in
glomerulonephritis
Urea and creatinine may be elevated
<- renal failure

9. 2.Estimate serum cholesterol
concentrations
3.Total cholesterol & LDL- cholesterol
elevated in most patients. HDL-
cholesterol is normal or decreased.
4. Blood sugar & glycosylated
hemoglobin tests for diabetes.
5. Hepatitis B and C serology, HIV
serology
6. Renal biopsy if cause is not clear
especially in an adult patient.

10. Management
• Treatment of nephrotic syndrome
involves three steps:
1.Measures to reduce proteinuria
2.Measures to control complications of
nephrotic syndrome
3.Treatment of underlying cause

11. Measures to reduce proteinuria
• If immunosuppressive drugs and other
measures against the underlying cause
do not benefit the patient
1.ACE inhibitors -> proteinuria,
intraglomerular pressure -> slows rate of
progression of renal failure. Prevents
development of haemodynamically
mediated FSG
2.NSAIDs -> proteinuria

12. Measures to control complications
of nephrotic syndrome
• Oedema -> salt restriction, rest,
judicious use of diuretics
• In severe cases -> I.V. salt-poor albumin
• Dietary proteins 0.8-1.0g/kg
• Vitamin D supplementation
• Hyperlipidaemia -> dietary restrictions,
lipid-lowering drugs
• Anticoagulants in patients with DVT or
arterial thrombosis

13. Measures to treat the underlying
disease
Minimal Change Disease
•Children – corticosteroids (prednisolone
60mg/m2 x 4wks, followed by alternate
day prednisolone 35mg/m2 for 4 additional
wks)
Children responding to steroid treatment in
1st
4 wks – “steroid responsive”, those who
relapse on withrawal –” steroid dependent”
•Patients with frequent relapses ->
cyclophosphamide 2mg/kg/day x 6 wks

14. Focal and segmental glomerulosclerosis
•Steroids (20-30% cases)
•Cylophosphamide, cyclosporin
Membranous glomerulonephritis
•Spontaneous remission (40%)
•30-40% cases remit and relapse repeatedly
•Rest 10-20% patients develop progressive
renal failure -> cyclophosphamide, cyclosporin
and chlorambucil in combination with steroids
may retard progression