The document provides a detailed overview of nephrotic syndrome, including its characteristics such as massive proteinuria, hypoalbuminemia, and generalized edema. It outlines various causes of the syndrome including primary glomerular diseases and systemic diseases, with a focus on conditions such as minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. The document further discusses the pathogenesis and morphological features associated with these conditions, highlighting the importance of diagnosing and understanding nephrotic syndrome in children and adults.

1. Nephrotic syndrome
4th year Block 2
Prof. Nadeem Nusrat
Faculty of Pathology
FRPMC

2. At the end of session the student will have an
idea of
• The structure of glomerulus
• Damage inflicted to glomeruli
• Difference between Nephrotic and Nephritic syndrome
• Various causes of Nephrotic syndrome
• Pathogenesis of Nephrotic syndrome

5. Nephrotic syndrome
• It is glomerular disease characterized by
1. Massive proteinuria: > 3.5 gms in 24 hrs ( less in children)
2. Hypoalbuminemia: < 3 gm/dl plasma albumin level
3. Generalized edema
4. Hyperlipidemia and lipiduria

7. Causes Approximate Prevalence
Primary Glomerular disease Children Adults
1 Membranous nephropathy 3 30
2 Minimal change disease 75 8
3 Focal segmental glomerulosclerosis 10 35
4 Membranoproliferative GN & dense deposit disease 10 10
5 Others: IgA nephropathy, focal, pure mesangial 2 17
Systemic diseases
1 Diabetes Mellitus
2 Amyloidosis
3 SLE
4 Drugs: NSAIDs, Penicillamine, heroin
5 Infections: Malaria, Syphilis, Hepatitis B & C
6 Malignant disease: Carcinoma, Lymphoma
Causes of Nephrotic Syndrome

8. Re-Cap: Features of Nephrotic syndrome
• Damage to BM in renal glomerulus
• Derangement in glomerular capillary walls
• Increased permeability through the damaged basement membrane
• Passage of high amounts of proteins particularly Albumin in urine
• Albuminuria and hypoalbuminemia
• Loss of immunoglobulin: Immunocompromised:
• Loss of natural anticoagulants:
• Loss of Anti-thrombin 111
• Hypercoagubiliity
• Thrombo-embolic phenomenon e.g. Renal vein thrombosis
• Loss of lipids in urine on a background of High cholesterol, TGs, VLDL, LDL

9. • Children: Most important cause of Nephrotic syndrome
• By primary renal lesions
• Minimal change disease
• Membranous nephropathy
• Focal segmental GN
• Adults: Most important cause of Nephrotic syndrome
• Diabetes Mellitus
• Amyloidosis
• SLE

11. Minimal change disease
• Most important cause of Nephrotic syndrome in children
• Occurs mostly in children with a peak incidence: age 2-6 years
• Usually idiopathic may be associated with Hodgkin lymphoma
• Sometimes follows a respiratory infection or routine immunization
• Some immune dysfunction occurs
• Elaboration of factors that damage podocytes
• Diffuse effacement of foot processes of podocytes in glomeruli

12. Normal

13. Morphology of Minimal change disease
• Normal glomeruli on H & E stains: Lipid may be seen in proximal tubule cells
• Effacement of foot processes on Electron microscopy
• No immune complex deposits
• Negative immunofluorescence
• Damage is mediated by cytokines and T cells
• Selective proteinuria (loss of albumin but not Immunoglobulins)
• Excellent response to steroids

14. Focal segmental Glomerulosclerosis
• Most common causes of Nephrotic syndrome in African Americans
• Usually idiopathic
• May be associated with HIV, Heroin use & Sickle cell disease
• Focal & segmental sclerosis on H &E stains( only some parts of glomeruli)
• Effacement of foot processes on Electron microscopy
• No immune complex deposits, negative immunofluorescence
• Poor response to steroids
• May progress to chronic renal failure

15. Membranous nephropathy
• Most common cause in adults (Caucasians)
• Usually idiopathic
• May be associated with Hepatitis B or C, SLE, Solid tumors or drugs
• Thick glomerular basement membrane on H&E
• Sub-epithelial Granular immune complex deposition
• Spike and doom appearance on Electron microscopy
• Poor response to steroids
• Progresses to Chronic renal failure

17. Diabetes mellitus
• Hyaline arteriosclerosis: Non enzymatic glycosylation of basement
membrane
• Efferent glomerular arteriole effected more than afferent resulting in
• High filtration pressure leading to
• Microalbuminuria
• Eventually progresses to chronic renal failure, characterized by
• Sclerosis of mesangium with formation of Kimmelstiel-Wilson nodules
• ACE inhibitors slows the progress

19. Amyloidosis
• Kidney is the most commonly organ in systemic amyloidosis
• Mesangium is effected resulting in Nephrotic syndrome
• Characterized by apple green birefringence under polarized light

20. Thanks