1. BY DR WAQAR MBBS, MRCP ASSISTANT PROFESSOR
NEPHROTIC SYNDROME
BY DR WAQAR
MBBS, MRCP
ASSISTANT PROFESSOR

2. DEFINITION Nephrotic Syndrome is characterised by :
Proteinuria( > 3.5g/day).Normal is <100mg/d
Hypoalbuminemia
Edema
Hyperlipidemia

3. PATHOGENESIS Proteinuria : Glomerular pathology increases
its permeability protein lost in the urine
Low serum albumin: Due to loss in the urine
Edema : Low serum albumin decreases oncotic
pressure, so fluid leaks into the interstitium
edema occurs.
Hyperlipidemia: Due to increased synthesis, and also loss of apoproteins in the urine( apoproteins are lipid carriers in the blood)

4. COMPARISON Nephrotic Nephritic Heavy proteinuria > 3.5g/d Edema
Hypoalbuminemia
Hyperlipidemia
Usually, no hematuria, no oliguria/uremia
HTN +/-
Proteinuria less than 2 g/d
Usually Oliguria (uremia)
HTN ( w/edema)
Hematuria

5. S/S of Nephrotic 1) Edema: * Periorbital * Ankles/ legs * Genitals
* Generalised ( anasarca)
2) HTN

6. Peri-orbital edema in nephrotic

7. CAUSES OF NEPHROTIC SYNDROME
We will discuss :
* Glomerular lesions which cause nephrotic
syndrome.

8. GLOMERULOPATHIES CAUSING NEPHROTIC SYNDROME
1) Minimal change disease
2) Membranous nephropathy ( MN)
3) Focal segmental glomerulosclerosis (FSGS)
4) Diabetic nephropathy
5) Deposition disorders
Some glomerular lesions can present with
mixed nephrotic/nephritic picture.

9. Minimal Change Disease (MCD)
1) It is the commonest cause of nephrotic syndrome in children ( etiology unknown) 2) In adults, MCD can occur secondary to: * Hodgkin’s disease * Solid tumors

10. MCD contd
Pathology :
Fusion of the foot processes of the podocytes ( seen on electron microscopy)
Light microscopy is normal
No immune deposits seen

12. Treat of MCD :
In children : Highly responsive to steroids
* Prednisone for 4-6 wks, then tapered
* Can be given again for a relapse
In adults: Less response to steroids
*Prednisone given for 8-12 wks, then tapered
* Can be repeated for a relapse
If very frequent relapses, or if steroid failure, give immunosuppressive therapy ( cyclophosphamide, cyclosporin, chlorambucil)
Prognosis : V.Good. No end stage renal disease

13. MEMBRANOUS NEPHROPATHY
Commonest cause of nephrotic syndrome in
adults.
1) Primary : Idiopathic (no known cause)
2) Secondary: Associated with
* SLE *Hepatitis B *Drugs (penicillamine,
gold) * Solid organ cancers
Pathology (biopsy)
* Deposits of IgG & C3( immune deposits)
* Thickening of glomerular basement memb-
-rane & “spike” formation.

14. Diagram of membranous nephropathy

15. M.N. ( spike pattern)

16. M.N. contd Treatment Good prognosis w/ high rates of recovery
Some patients no Rx
Rx given if high risk of progression
Rx : * Prednisone * Immunosuppressives
* Rituximab (new drug)

17. FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Primary
Secondary : Associated with HIV, Obesity
( HIV can also cause other glomerulopathies)
Pathology: Sclerosis & immune deposits in some glomeruli,not all (so focal) and “parts” of
glomeruli affected not the whole(segmental)

18. FSGS (contd) TREATMENT
Steroids: Can be tried but not very good response
In case of relapse, cyclophosphamide, cyclosporin (immunosuppressives)
Prognosis : Can progress to renal failure
(25% pts. at 5 yrs)

19. WHY IT IS CALLED FOCAL SEGMENTAL
WHY IT IS CALLED FOCAL SEGMENTAL? * Focal : Only some glomeruli are affected * Segmental : only parts of the glomerulus are affected, not the whole glomerulus

20. DIABETIC NEPHROPATHY Most common cause of ESRD
Starts w/microalbuminuria (30-300mg of albumin lost in 24 hrs. urine)
Progresses to macroalbuminuria finally
causes nephrotic syndrome (>3.5g/d)
Pathology : * Sclerosis in the glomerulus & mesangium ( Kimmelstein Wilson nodules)
* No immune deposits * Thick basement memb.

21. DM nephropathy (contd)
TREATMENT
1) Strict DM control
2) ACE inhibitors ( first choice), or ARBs
3) Annual screening for proteinuria in DM patients. (Dipstix can not detect microalbuminuria, so do microscopic urinalysis)
( ACE inhibitors can slow & even reverse
proteinuria)

22. DIABETIC NEPHROPATHY

23. DEPOSITION DISEASES Amyloidosis, Light chain deposition disease,
multiple myeloma
Renal biopsy shows amyloid deposition in amyloidosis, Ig chain deposition in “Light chain deposition disease”.
Multiple myeloma causes amyloidosis and so causes nephrotic syndrome
Rx: According to the cause

24. GENERAL Rx OF NEPHROTIC SYNDROME
For Edema :
a) Salt & water restriction
b) Diuretics ( first thiazides, if no response,
then furosemide (Lasix)
2) Normal protein diet
* Don’t take high protein diet will worsen
proteinuria & renal damage
* Protein <80g/d

25. GEN. Rx contd. 3) For proteinuria :
* Use ACE inhibitors ( 1st choice) or ARBs
( name 3 common S/E of ACE)
4) For High Cholesterol : ( pts. Wth nephrotic
have high cholesterol)
* Diet * drugs ( statins)
5) Pneumovac ( vaccine against pneumococci)
every 5 yrs,& flu vaccine every yr.
HTN : If present, ACE inhibitors will take care
of it.

26. COMPLICATIONS OF NEPHROTIC SYND.
1) Thrombosis
Loss of anticoagulant proteins(antithrombin)
in the urine causes hypercoagulable state
Increased risk of DVT, renal vein thrombosis
Treated w/ heparin and then warfarin
Prophylaxis is controversial ( some people suggest it in membranous nephropathy because there is high risk of thrombosis in that condition).

27. Complications (contd)
2) Infections/Sepsis * Due to urinary loss of immunoglobulins * Treat infections aggressively * Common cause of death in nephrotic pts. 3) Increased lipids in the blood

28. SUMMARIZE Causes of nephrotic syndrome at a glance
Minimal Change Disease( primary, Hodg-
kin’s, NSAIDs)
2) Membranous nephropathy(primary, SLE, Hep
B, malignancies, drugs like gold, penicillamine)
3) FSGS ( HIV)
4) Diabetic Nephropathy
5) Deposition Disorders( amyloidosis, Multiple
myeloma)

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