Know the Light Microscopy, Immunofluorescenc, and Electron Microscopy findings in Focal Glomerular Sclerosis

• Light Microscopy

• Segmental lesions may be missed if not enough glomeruli in biopsy

• Involvement of juxtamedullary glomeruli

• Sclerotic segments show collapse of BM, increase in matrix, and hyalinosis

• Lipoid droplets and foam cells often present

• Even ‘uninvolved’ glomeruli may show mesangial proliferation

• Immunofluorescence - IgM and C3 present in hyaline masses

• Electron Microscopy

• Effacement of foot processes

• Pronounced focal detachment of the epithelial cells with denudation of the underlying GBM

Know the clinical presentation of the majority of patients with Focal Glomerular Sclerosis

• FSG is associated with a higher frequency of hematuria and HTN than other idiopathic presentations of nephrotic syndrome

• Sterile pyuria is common

• Proteinuria is nonselective and occasionally may be asymptomatic

Know that there is a high rate of recurrence of the disease in the grafts, especially in well-matched grafts

• Nephrotic syndrome
• FSG
• HTN
• Rapidly progressive renal disease

Why has FSG incidence decreased in recent years?

• Increases in purity of ‘street’ heroin

Know the kidney diseases that can be associated with drug addiction

• 25% of FGS

• 10% of end-stage renal disease

• also GN secondary to bacterial endocarditis, hepatitis B, etc.

1. Know that Membranous Nephropathy is the most common cause of NS in adults

2. Name the causes of secondary Membranous Nephropathy
   

   • Drugs – penacillamine, gold, captopril

   • Infection – hepatitis B, syphilis, various parasitic diseases

   • SLE – careful to check for in young women with Membranous Nephropathy
     

   • Malignancy

• Especially in lung, breast, and GI

• Important to check for in older patients with Membranous Nephropathy
  

• Sjogren’s syndrome
• Mixed connective tissue disease
• Systemic metabolic disorders – e.g, diabetes, thyroiditis
• Sickle cell disease
  

3. Know the Light Microscopy, Immuno Fluorescense, and Electron Microscopy findings of Membranous Nephropathy
   

• LM

• Glomeruli appear normal early in disease
• Later, diffuse thickening of capillary walls occurs
• Silver stain demonstrates spikes in BM between deposits
• Trichrome stain may reveal deposits themselves

• IF – diffuse, granular pattern of IgG and C3 deposits along subepithelial surface of capillary loops
• EM - Electron dense deposits in subepithelial distribution with effacement of overlying foot processes

4. Know the age, clinical manifestations and HLA antigens of patients with Membranous Nephropathy
   

• Mean age of onset is 40-50
• Most present with nephrotic syndrome (~20% with asymptomatic proteinuria)
• Microscopic hematuria present in ~60%
• RBC casts rare
• HTN is uncommon
• Renal function is usually normal
• IC in blood is RARE – complexes are formed in situ
• Similar to Heymann nephritis in rats  linked to HLA locus  caused by susceptibility to Ab to a renal auotoantigen
  

5. Know how to work up a case of Membranous Nephropathy
   

• Determination of antinuclear and antiDNA Ab, serum complement, rheumatoid factor, cryoglobulin, Hepatitis B Ag, VDRL, and tests to exclude diabetes

• Older patients should have a clinical and radiologic search for occult malignancy

• Hematuria and flank pain may indicate pulmonary emboli

• May have other glomerular disease “ on top of ” Membranous Nephropathy
  

6. Know the prognosis of Membranous Nephropathy
   

• Widely variable clinical course

• 25% -Spontaneous remission

• 25% have persistent nephrotic range proteinuria for many years while maintaining normal renal function

• Remaining 50% show progressive deterioration of renal function that results in end-stage renal disease in about 15 years

• No criteria have been identified to predict which course an individual will follow