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Primary Glomerular diseases causing nephrotic syndrome (Ref. Hari. 18th ed., Ed., Pg - 2345)

A. Minimal Change Disease
  1. This occurs commonly in children.
  2. The blood pressure is normal.
  3. GFR is normal or slightly reduced. No significant urinary sediment is seen.
  4. Proteinuria in the nephrotic range is present.
  5. Selective proteinuria is seen (there is selective excretion of low molecular weight protein like albumin and absence of high molecular weight protein like globulin in the urine).
  6. Selective presence of low molecular weight protein in urine indicates a good prognosis.
Mechanism of proteinuria in minimal change disease (MCD)

Effacement of foot process (Earlier called fusion of foot process) is believed to play an important role in causes proteinuria in MCD. Proteinuria occur due to.
  1. Loss of negative charge (Loss of polyanions)
  2. Disruption of components of slit diaphragm (Demonstrated in congenital nephrotic syndrome of the Finnish type)
  3. Loss of actin cytoskeleton
Investigation Observation
Light microscopy No abnormality seen
Electron microscopy Fusion of foot processes
Immunofluorescence Absence of immunoglobulin or complement
Causes (AIPG 2010)
  1. Idiopathic
  2. Drugs – NSAID, rifampicin, IFN – alpha
  3. Hodgkin’s disease
  4. HIV

Hepatitis B is not a cause of Minimal change glomerulopathy.

Rarely minimal change GN it may progress to Focal & Segmental glomerulosclerosisQ (AIIMS Nov 10)

Treatment of minimal change GN (Ref. Hari. 18th ed., pg - 2345)
  1. Prednisone is first-line therapy, 
  2. Other immunosuppressive drugs, such as cyclophosphamide, chlorambucil, and mycophenolate mofetil, are saved for frequent relapses, steroid-dependent, or steroid-resistant patients. 
  3. Cyclosporine can induce remission, but relapse is also common when cyclosporine is withdrawn.
B. Membranous GN (Ref. Hari. 18th ed., pg - 2347)

This occur commonly in adults

Conditions Associated with Membranous Glomerulopathy
  1. Idiopathic (majority)
  2. Infection: Hepatitis B and C, secondary and congenital syphilis, malaria, schistosomiasis, leprosy, hydatid disease, filariasis, enterococcal endocarditis
  3. Systemic autoimmune diseases
    SLE, rheumatoid disease, Sjorgren’s syndrome, Hashimoto’s disease, Graves’ disease, mixed connective tissue disease, primary biliary cirrhosis, ankylosing spondylitis, dermatitis herpetiformis, bullous pemphigoid, myasthenia gravis
  4. Neoplasia
    Carcinoma of the breast, lung, colon, stomach, and esophagus; melanoma; renal cell carcinoma; neuroblastoma; carotid body tumor
  5. Drugs: Gold, penicillamine, captopril, NSAIDs, probenecid, trimethadione, chlormethiazole, mercury
  6. Miscellaneous
    1. Sarcoidosis
    2. Diabetes mellitus
    3. Sickle cell disease
    4. Crohn’s disease
    5. Guillain – Barre syndrome
Clinical Features
  1. Patients present with edema, nephrotic proteinuria and high BP. 
  2. Renal insufficiency and abnormal urine sediment may develop later. 
  3. Renal vein thrombosis is common. 
  4. Complement levels are normal
C. Focal and Segmental Glomerulosclerosis (FSG)

This accounts for about 10 – 15% of idiopathic nephrotic syndrome.

It is more commonly seen in adults in the age group of 20 – 30 years.

Etiology of Focal and Segmental Glomerulosclerosis
  1. Idiopathic (majority)
  2. In associated with systemic diseases or drugs:
    1. HIV infection
    2. Diabetes mellitus
  3. As consequence of sustained glomerular capillary hypertension
    1. Congenital oligo nephropathies
    2. Unilateral renal agenesis
    3. Reflux nephropathy
    4. Glomerulonephritis or tubulointerstitial nephritis
    5. Sickle cell nephropathy
    6. Heroin use
  1. Proteinuria is present and is usually nonselective.
  2. Hypertension, reduced GFR, abnormal tubular function and abnormal urinary sediments (leukocyturia, hematuria) are seen.
  3. Hyperlipidemia is severe in cases with focal sclerosis.
    Prognosis is variable. In steroid responsive patients, prognosis is good, but in steroid unresponsive patients and in patients with heavy proteinuria rapid progression to end stage renal failure occurs within a few months. Cyclosporine or tacrolimus, as an adjunctive therapy to steroids, may be beneficial in some cases. 
Important Points
  1. FSGS may develop following acquired loss of nephrons from reflux nephropathy.
  2. Proteinuria is nonselective in most case and may be in (Nephritic range) or nephrotic range.
  3. Association of reflux nephropathy and proteinuria suggest an irreversible glomerular lesion most commonly FSGS
  1. Therapy
    1. Prolonged glucocorticoid therapy (i.e., >6 months) may lead to remission of proteinuria.
    2. Cyclosporine as well as ACE inhibitors may be effective in reducing proteinuria.
  1. Membranoproliferative Glomerulonephritis
Table 283-4 Membranoproliferative Glomerulonephritis (Ref. Hari. 18th ed., Pg - 2344)
  1. Type I Disease (Most Common) due to classical complement pathway
    1. Idiopathic
    2. Bacterial endocarditis
    3. SLE
    4. Hepatitis C (AIIMS Nov 2012)
    5. Mixed cryoglobulinemia
    6. Hepatitis B
    7. Cancer: Lung, breast, and ovary (germinal)
  2. Type II Disease (Dense Deposit Disease) due to alternative pathway
    1. Idiopathic
    2. C3 nephritic factor–associated
    3. Partial lipodystrophy
  3. Type III Disease (Subepithelial deposit + type I, C3 is deposited)
    1. Idiopathic
    2. Complement receptor deficiency
Clinical Feature
  1. They present with microscopic to gross hematuria and selective or non-selective proteinuria depending on the severity of the disease. 
  2. They have a poor prognosis, developing renal failure 5-10 years after diagnosis.
  3. Complement level is reduced
Summary of Pathology of Primary Glomerular diseases.
  1. Minimal change GN – Loss of foot process
  2. Membranous (Heyman’s) GN – Sub epithelial deposition, spike and dome pattern.
  3. FSGS – Loss of foot process, Mesangial deposition, detachment of basement membrane from epithelium.
  4. MPGN – Mesangial cell proliferation, Splitting of BM (Tram track appearance)
    Type I – Subendothelial deposition
    Type II – Intramembranous deposition
  5. Post streptococcal GN - Sub epithelial, Intramembranous and Sub endothelial deposition.
  6. RPGN – Crescent formation by multiplying of parietal epithelial cells.
  7. Good pasture – Intramembranous deposition of immunocomplex.
Important Points

Compliment levels are normal in

  1. Minimal change GN
  2. Membranous GN
  3. FSGS

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