Nephrotic syndrome is a kidney condition characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia. It can be caused by primary kidney diseases like minimal change disease or secondary causes such as diabetic nephropathy. Patients present with edema, thromboembolic risks, infections, malnutrition, and bone fractures due to proteinuria. Diagnosis involves urine protein estimation through 24-hour urine collection or spot urine protein:creatinine ratio. Treatment focuses on managing the underlying cause, complications, and reducing proteinuria with ACE inhibitors.

1. NEPHROTIC SYNDROME

2. WHAT IS IT?
A glomerular disease characterized by heavy protreinuria
(>3.5gm/day) with hypoalbuminaemia, oedema, hyperlipidaemia
and lipiduria

3. CAUSES OF NEPHROTIC SYNDROME
A)PRIMARY CAUSES
Nephrotic syndrome due to kidney disease:
1. Minimal change disease (MCD)
2. Focal segmental GN(FSGN)
3. Membranoproliferative GN(MPGN)
4. Membranous GN (MGN
B) SECONDARY CAUSES
1. Diabetic nephropathy
2. SLE
3. Amyloidosis
4. PSGN
5. Malignancy
6. Drugs (gold, NSAID, penecillamine)
7. HIV

4. CLINICAL PRESENTATION
1. OEDEMA
2. THROMBOEMBOLIC EVENT
a) Deep venous thrombosis (DVT)
b)Pulmonary embolism (PE)
c) Renal vein thrombosis (RVT)
3. Infection
4. Malnutrition
5. Bone fracture
6. Uncommonly hypertension
7. Rarely uraemia
8. Primary disease causing NS

5. PROTEINURIA ESTIMATION
NEPHROTIC SYNDROME
Urinary protein excretion can be quantified by:
A) 24hr urine collection, which is:
1. Difficult
2. Cumbersome and
3. Expensive
B) Random spot urine
1. Protein:creatinine ratio
2. Albumin:creatinine ratio

6. 24 HOUR URINE COLLECTION
Ask the patient to:
1. Collect a special bottle from the laboratory
2. Chose a day for collection, say Sunday.
3. Must empty the bladder in the toilet on Sunday at 8am.
4. Thereafter, MUST, pass all the urine in the bottle.
5. Must empty the bladder into the bottle on Monday at 8am.
6. Any urine passed after 8am on Monday must be discarded.

7. RANDOM SPOT URINE
1. IT IS EASY AND CONVINIENT.
2. IT MEASURES URINARY PROTEIN IN RELATION TO CREATININE.
3. A URINE:CREATININE RATIO OF 5 IS CONSISTENT WITH 5G PER
DAY PER 1.73M²

8. PROTEINURIA AND OEDEMA
IN NEPHROTIC SYNDROME
1. Proteinuria leads to hypoalbuminaemia
2. Hypoalbuminaemia leads to reduction in intravascular oncotic
pressure.
3. Low oncotic pressure leads to movement of fluid into the
interstitial space.
4. Fall in the intravascular volume stimulates release of renin and
aldosterone
5. This leads to sodium and water retention.
6. The oedema worsens

9. NEPHROTIC SYNDROME AND
LIPIDS
1. ↓IN INTRAVASCULAR ONCOTIC PRESSURE
2. ↑ LIVER SYNTHESIS OF PROTEINS INCLUDING LIPOPROTEINS
3. THESE ARE FILTERED IN THE GBM.
4. HENCE:
a) Hyperlipidaemia leading to accelerated atherosclerosis, seen commonly
in NS.
b) Hyperlipiduria

10. THROMBOEMBOLISM AND
NEPHROTIC SYNDROME
• Hypercoagulabilty is very common in nephrotic syndrome due to many
factors:
1. Urinary loss of anticoagulants:
a) Antithrombin 111.
b) Protein S
c) Protein C
2. Platelet hyperaggregability
3. ↑liver synthesis of procoagulant proteins
COMPLICATIONS:
a) Deep venous thrombosis (DVT)
b) Pulmonary embolism (PE)
c) Renal vein thrombosis (RVT)

11. NEPHROTIC SYNDROME AND
BONE FRACTURES
1. Urinary loss of 25(OH)D binding protein.
2. ↓ 25(OH)D₃
3. Deficiency of 1,25(OH)₂D₃
4. Secondary hyperparathyroidism (↑PTH)
5. Bone fracture.

12. NEPHROTIC SYNDROME AND
INFECTION
The urinary protein loss in nephrotic syndrome may include loss
of:
a) Immunoglobulins(IgG).
b) Compliment proteins
c) Impaired cell mediated immunity
This leads to:
1. IgG deficiency
2. Poor bacterial opsonization.
Increased risk of infection by encapsulating bacteria (Strep pneumonia, H.
influenzae, E.Coli)

13. LABORATORY EVALUATION OF
NEPHROTIC SYNDROME
• If the primary disease is know, like DM, further unnecessary tests are not
beneficial.
• Some patients may require further evaluation:
• FBC
• Renal immunological studies including C3, C4 levels
• Serum immunoelectrophoressis
• Urinary immunoelectrophoresis
• CXR
• Stool for occult blood
• Hepatitis serology
• HIV
• Renal biopsy in adults

14. MANAGEMENT OF
NEPHROTIC SYNDROME
This depends on the cause.
TREAT THE:
a) Underlying disease (or secondary cause)
b) Complications (oedema, hyperlipidaemia, infection, thrombosis, hypertenstion, renal failure)
c) Proteinuria

15. TREATMENT OF
PROTEINURIA
1. ACEI OR ARB.
2. LOW SALT DIET.
3. VITAMIN D SUPPLEMENT

16. THROMBOEMBOLISM IN
NEPHROTIC SYNDROME
1. Use of anticoagulant remains contraversal.
2. Start with Heparin and warfarin.
3. Cease Heparin on the third day.
4. Continue with oral.
5. Monitor INR

17. OEDEMA MANAGEMENT IN
NEPHROTIC SYNDROME
1. DAILY WEIGHT
2. INPUT OUTPUT CHART
3. USE HIGH DOSE LOOP DIURETICS I.V.
4. ADD THIAZIDE DIURETICS IF POOR RESPONSE.
5. MONITOR THE ELECTROLYTES
6. REPLACE POTASSIUM IF TOO LOW.

18. END

19. MINIMAL CHANGE DISEASE
(MCD)
Definition:
Kidney disease characterized by nephrotic syndrome with
normal histology on light microscopy and immunofluorescence
but an effacement and widening of epithelial cell foot
processes(podocytes)on electron microscopy.

20. CAUSES OF MCD
1. Not known
2. Viral or bacterial infection
3. Activation of immune response leading to
formation of Immune-complex disease.
1. This explains why it has good response to treatment with steroids.

21. INCIDENCE OF MCD
1. COMMON CAUSE OF IDIOPATHIC NS:
a) Adult 10 – 20%
b) Children 70 – 90%
2. SEX: MALES > FEMALES (3:2 ratio)
3. Age group: 2 – 6 years

22. CLINICAL PRESENTATION OF
MCD
1. OVERT NEPHROTIC SYNDROME
2. NORMAL BLOOD PRESSURE
3. MILDLY IMPAIRED RENAL FUNCTION
4. MINIMAL HAEMATURIA
5. HIGHLY SELECTIVE PROTEINURIA
6. NORMAL SERUM C3, C4

23. DIAGNOSIS OF MCD
1. Presents as nephrotic syndrome in children
2. Good response to therapy
3. Renal biopsy not necessary
4. Is uncommon in older children (>10years), presence of haematuria, AKI,
hypertension, raised serum creatinine). In this situation, renal biopsy
maybe warranted prior to initiation of therapy.
5. Renal biopsy is mandatory in adults with suspected MCD to
make the diagnosis.

24. STANDARD TREATMENT OF
MINIMAL CHANGE DISEASE
1. High dose prednisolone 20mg TID for 2- 6 weeks(to prevent
relapse).
2. Reduce prednisolone to 40mg single dose on alternate days
for 1 month.
3. Then start tapering over 2 months.
4. Cease the treatment at the end of the 2 months.
5. LSD is recommended

25. COMPLICATIONS OF
MCD
1.Increased risk of infection with encapsulated organisms (Strep pneumonie, E.
coli, H. influenzae) due to:
1.1 Loss of antibodies and complement proteins.
1.2 Defective cell mediated immunity.
2. Hypercoagulability
2.1 Venous thrombosis (DVT)
2.2 Arterial thrombosis
2.4 Just due to aggressive diuresis
3. Bone disease
3.1 Vitamin D deficiency
3.2 SHPTH

26. PROGNOSIS
1. About 75-80% go into remission within 2weeks
2. Approximately 60-75% of children with MCNS will at least
have one relapse
3. Relapse rate is much higher in adults
4. Some patients may be steroid dependent ie go into remission,
while on treatment but relapse when steroid is ceased.

27. TREATMENT OUTCOMES OF MCD
1. Complete remission:
1.1 May be spontaneous or
1.2 With steroids therapy.
2. Relapse:
2.1 Frequent relapses ( 2 relapses within 6months)
3. Steroid dependent:
Patient goes into remission, but relapses when steroid dose is papered or ceased within 4 weeks.

28. Treatment of steroids in MCD
1. Repeat doses of steroids 60mg/day in divided doses for 3 days
2. ↓ steroid dose to 40mg/day on alternating days for 4 weeks.
3. Continue papering steroids until minimal dose, with no
recurrence.
4. Refer to nephrologist for possible imunosuppressive therapy.

29. END

30. DIABETIC NEPHROPATHY
Definition:
Progressive kidney disease due to long standing diabetes
mellitus (type 1 or 2), characterized by the presence of proteinuria
or frank nephrotic syndrome.

31. DIABETIC NEPHROPATHY
PATHOLOGY
. Pathogenesis of diabetic kidney disease is complex and poorly
understood. It is basically associated with persistent
hyperglycaemia or poorly controlled diabetes mellitus.
. It causes unique structural changes in the kidney culminating
into nodular glomerulosclerosis, the Kimmelstiel-Wilson nodules.
This classical histological finding is pathonognomic of DN, but is
only found in 10-20%

32. RISK FACTORS OF
DIABETIC NEPHROPATHY
1. FAMILIAL SUSCEPTIBILITY
2. HYPERGLYCAEMIA
3. PROTEINURIA
4. CIGARATTE SMOKING
5. DYSLIPIDAEMIA

33. OTHER ASSOCIATED
CLINICAL PRESENTATION
1. Long standing history of DM
2. Good or poor glycaemic control.
3. Presence of diabetic retinopathy as in type 1
4. Detection of microscopic proteinuria (albumin)
5. Rarely, presence of microscopic haematuria.

34. COMORBID ASSOCIATION WITH
DIABETIC NEPHROPATHY
1. Diabetic retinopathy
2. Peripheral neuropathy
3. Cardiovascular diseases(coronary heart disease)
4. Vascular diseases(Carotid, atherosclerotic renal artery stenosis)

35. PREVENTION OF
DIABETIC NEPHROPATHY
ABSOLUTE CONTROL OF RISK FACTORS:
1.HYPERTENSION
2.HYPERGLYCAEMIA
3.SMOKING
4.DYSLIPIDAEMIA
5.HIGH SALT INTAKE
These are also risk factors for CVD

36. MANAGING DIABETIC NEPHROPATHY
1. HYPERTENSION;
1.1 Start with ACEi or ARB
1.2 Add on CCB (Nondihydropyridine)
1.3 Then beta blocker
2. HYPERGLYCAEMIA
2.1 Aim at HbAiC <6%
2.2 Remember as the GFR deteriorate, the insulin requirement drops.
3. PROTEINURIA
3.1 ACEi or ARB
3.2 Pentoxifylline (an old drug but new function)

37. END