Updated review of Nephrotic syndrome.

1. Dr Gabriel Guevara - 2024 Review
NephroticSyndrome

2. Definition
The term "nephrotic syndrome" refers to a distinct constellation of
clinical and laboratory features of kidney disease.
It is specifically defined by the presence of heavy proteinuria (protein
excretion greater than 3.5 g/24 hours), hypoalbuminemia (less than 3.5 g/
dL), and peripheral edema.
* Overview of heavy proteinuria and the nephrotic syndrome, UptoDate 2022

3. Pathophysiology
Etiology
Podocyte
effacement
Podocyte effacement
1.
2.

4. Pathophysiology - Clinical presentation
Podocyte
effacement
Proteinuria >3.5g/day
RAAS activation
Liver response
Hypoalbuminemia
Hypogammaglobulinemia
Anti-thrombin III def.
Edema
Immunede
fi
cient
Procoagulative state
HTN
MORE EDEMA
Hyperlipidemia
Hyperlipiduria
Fat oval bodies

5. Clinical presentation Summary
- Hyponatremia
- Albumin decrease
- Proteinuria >3.5g/d
- Hyperlipidemia
- Renal vein thrombosis
NAPHROTIC
- Orbital edema (lower limb)
- Thromboembolism
- Infection
- Coagulability

6. Etiology
Primary causes
Minimal Change Disease Membranous Nephropathy
Focal Segmental
Glomerulosclerosis
Idiopathic, URTI, NSAID, Hodgkin
Lymphoma
Hepatitis B, C, Syphilis, Gold,
Penicillamine
Heroine use, HIV and Sickle cell
disease
Mediated by Cytokines
Anti PLA 2 receptor antibodies,
Spike and dome appearance.
Hyalinosis and Sclerosis in the
glomerular structure

7. Etiology
Secondary causes
Diabetes
1. Uncontrolled
hyperglycaemia
2. Non enzymatic
Glycation of EA causing
Narrowing
3. Hyper
fi
ltration
4. Mesangial cell
release TGF Beta
5. Hyaline sclerosis of
glomerular structures
Kimmelstiel Wilson
Nodules
6. Decrease in GFR +
Podocyte effacement

8. Etiology
Secondary causes
Amyloidosis
• Chronic in
fl
ammatory
states
• Multiple myeloma

9. Diagnostics
1. Suspect
- NAPHROTIC
2. Urinalysis and Microscopy
Nephrotic syndrome Nephritic Syndrome
Protenuria >3.5g/d Proteinuria <3.5g/d
Fat oval body RBC cast ****
Lipiduria Sterile Pyuria (WBC)

10. Diagnostics
3. 24 hour urinary protein or UACR >3.5g/d
- 24 hour test needs more labour collecting urine for 24 h
- Urinary Albumin Creatinine Ratio doesn’t need to wait can be done in the spot
4. Serum albumin level
- Hypoalbuminemia <3.5g/dL
5. Lipid panel
- VLDL, LDL, TGL (Hyperlipidemia)
Nephrotic Syndrome!!!

11. Diagnostics
Look for the clues!!
- Children, HL, NSAID, URTI —————Minimal Change disease
- Hepatitis B, C, Syphilis, Gold penicillamine ——Membranous Neph.
- HIV, Heroin use, sickle cell disease ————Focal segmental Glomerulosclerosis
- Diabetes —————— Diabetic Nephropathy
- Rheumatoid arthritis, Multiple myeloma ————Amyloid associated Nephropathy
What is the cause?

12. Diagnostics
Corticosteroid trial
- If primary cause suspected (no diabetes no amyloidosis)
- If good response to it might be Minimal Change Disease
- No good response Biopsy

13. Biopsy
MCD MN FSGS Diabetic Nephropathy Amyloidosis
Light microscopy
NORMAL
Light Microscopy
thickened GBM
LM: Hyalunosis and
sclerosis segmental
LM: Kimmelstiel
wilson nodules
LM nodular sclerosis
Immuno
fl
uorescense
NORMAL
Immuno
fl
uorecense
Lights up!
IF: Normal
EM: Podocyte
e
ff
acement
CONGO RED STAIN
Electron Microscopy
PODOCYTE
EFFACEMENT
Electron microscopy
spike and dome
Electron microscopy
podocyte e
ff
acement

14. Management
1. Proteinuria
Low protein diet, ACE inhibitors or ARBS
2. Edema
Fluid restriction, sodium restriction and Loop diuretics
4. Hyperlipidemia
Low Fat diet and statins
5. Infections
Antibiotics

15. Management
6. Procoagulative state
Anticoagulation
TREATING THE CAUSE
If it is a secondary cause its only going to improve if we treat the underlying cause
If it is a primary cause:
1. Start with corticosteroids
2. If not good response (do biopsy) look for MN or FSGS
- Cyclophosphamide
- Rituximab - Tacrolimus
CKD RISK!!!!!

16. “The good physician treats the disease: the
great physician treats the patient who has the
disease”
- Sir William Osler

17. Thanks for your attention!