• capillaries (derived from afferent hilar arteriole and merge at the efferent arteriole)
  • lined by fenestrated endothelium
  • large surface area (necessary for filtration)
• basement membrane
• visceral epithelial cells
  • contain negatively charged foot particles that cling to outer aspect of BM
  • function- pinocytosis and trap proteins that escape BM
• mesangial cells
  • function- contract and expand to regulate glomerular BF, thus glomerular filtration
    • potentially phagocytic

• function- major barrier to the passage of proteins
  • strong negative charge that repel primary anionic serum proteins
• synthesized by endothelial and epithelial cells
• does not completely encircle the lumen
  • incomplete on mesangial aspect being contiguous with the mesangial matrix

• allows water, electrolytes, small molecular weight compounds to pass into urine
• prevent loss of most protein serum
  • mainly due to strong negative charge, esp. with small plasma proteins like albumin

• earliest manifestation of glomerular BM damage
• <150 mg protein excreted per day
• serum protein concentration normal
  • rate of protein loss does NOT exceed ability of the liver to increase its synthetic rate

• urine protein and albumin excretion increases upon exercise
• urine protein excretion increases upon fever, stress, standing for prolonged periods

• proteinuria (excess of 3 grams/day)
• hypoalbuminemia (less than 2 grams/dL)
• edema (usually around eyes and progress to dependent parts of body)
• hypercholesterolemia
  • due to increased synthesis of all proteins including lipoproteins by liver
  • normally lipoproteins not excreted even with severe glomerular injury
    • but some are filtered than absorbed, so you may see lipid in the urine as droplets within tubular cells (oval fat bodies)

• proteinuria, hematuria, and often red cell casts in urine
  • manifest via loss of protein and RBC's
• decrease GFR- could cause decrease in urine output, leading to
  • edema (due to lack of excretion of salt and water in normal amounts)

1. capillary loops are disrupted
2. this allows cytokines, chemokines to pour into Bowman's space
3. leads to activation and proliferation of the parietal epithelial cells with associated inflammatory cells, forming a crescent
   • crescent glomerulonephritis = severe damage to glomerulus
4. proliferation of these cells together with various degrees of messangial and endocapillary hypercellularity, compresses the glomerulus
5. this precludes filtration acutely
6. if untreated, schlerosis ensues rapidly, causing atrophy of affected nephron
   • RPGN associated with rapid loss of renal function
   • one of the few renal emergencies associated with renal biopsy
   • cause oliguria, hematuria

• urinalysis
• urine microscopy
• quantification of urine protein
• measurements of serum creatinine
• BUN
• GFR
• creatinine clearance
• serum complement
• serum autoAb

• indirect measure of activation of immune system
• if you activate complement pathway, complements present in highest concentration are low
  • C3 and C4 decreased
• activation of alternative pathway:
  • C3 decreased
  • C4 normal
  • especially seen in membranoproliferative glomerulonephtritis

• find autoimmune diseases that cause glomerular inflammation
  • SLE associated with ANA Ab's
  • Goodpastures syndrome with anti-GBM
  • Wegner's granulomatosus associated with      c-ANCA
  • microscopic polyarteritis associated with ANCA

• light microscopy
• immunofluoroscence microscopy
• electron microscopy

• evaluates what:
  • BM thickening
  • glomerular hypercellularity
  • glomerular sclerosis
• patterns of sclerosis
  • focal (less than 50% of glomeruli involved)
  • diffuse (all/more than 50% of glomerul involved)
  • segmental (only part of an individual glomerulus affected)
  • global (all parts of individual glomerulus affected)

• proliferative is used to indicate an increase in number of cells within glomerulus, whether inflammatory cells or mesangial cells
• hypercellularity can involve mesangial compartment, capillary lumens (endocapillary hypercellularity), Bowman's space (extracapillary hypercellularity or crescent formation)
• membranous refers to involvement of capillary BM often leading to increase in thickness of loop

• fluorescent labeled Ab against human Ig's and complement are individually incubated with sections of kidney
• presence of any Ab which are concentrated in kidney will be detected as areas of fluorescence
• Ab's which are directed against Ag's normally present in pancreas form a linear pattern of fluorescence
• Ab's to Ag-Ab complexes are trapped in kidney and produce a granular fluorescent pattern

• evaluates BM at ultrastructural level, providing great detial of structure of BM
• presence of immune complexes can be confirmed and their locations within BM can be determined
• immune complexes appearr as well defined densities and are termed deposits

• minimal change disease
  • lipoid nephrosis/nil disease
• membranous nephropathy
• diabetic glomerular damage
• amyloidosis

• epidemiology
  • most common nephrotic syndrome in children
• prognosis
  • good response to corticosteroids
  • prolonged remissions typical in children
  • recurrences of nephrotic syndrome that resonpd to steroids do occur
  • not good prognosis in adults, and progressive loss of renal function may occur

• etiology- unknown
• pathogenesis
  1. stimulation of immune response
  2. visceral epithelial cell injury and BM damage induced by cytokines
  3. leads to loss of negative charge on BM
  4. protein leaks

• light microscopy and immunofluorescence
  • glomerulus appears morphologically normal
• EM
  • widespread fusion of effacement of visceral epithelial cell foot processes (nonspecific response to injury)
  • degree of foot process fusion is not specific for minimal change disease
    • can be seen in any case with severe proteinuria

• epidemiology- most common cause of nephrotic syndrome in Caucasian adults
• prognosis
  • 1/3 spontaneously recover
  • 1/3 respond to therapy with some decrease in renal function
  • 1/3 progress to renal failure
  • coricosteroids have not een shown to be3 of clear help
  • disease can recur in renal transplants or de novo

1. slow accumulation of Ab-Ag complexes in BM
   • in some cases, nature of Ag known (ex: hep B virus, lupus nephritis)
   • in most cases, it is unknown
2. proliferation of BM around complex does not prevent membrane from dysfunction, leading to proteinuria and nephrotic syndrome

• light microscopy
  • variable, but diffuse thickenin of BM depdning on stage of disease
• immunofluorescence
  • small-moderate sized granular deposits of IgG and complement (C3) seen in an even line alon glomerular BM
• EM- deposits on subepithelial side of BM

• nonenzymatic attachment of glucose to intrinsic glomerular proteins retards normal rate of replacement, and allows their accumulatiomn
• accumulation of glycosylated proteins from serum and hemodynamic changes leading to glomerular hypertrophy

• light microscopy
  • glomeruli with variable degrees of mesangial matrix expansion by BM like material
  • capillary loops pushed to edge of tufts and eventually Kimmelstiel Wilson nodules with marked mesangial lobulation are seen
  • seccondary glomeruloscleorosis
  • tubulointerstitial inflammation
  • fibrosis and arterial hyalination
• immunofluorescence and EM
  • confirm lack of immune complexes with thickened capillary loops and expanded mesangium

once developed, progressive loss of renal mass and chronic renal failure eventually develop

• mechanism
  1. accumulation of insoluble, fibrillar polymers in glomeruli starting at mesangial regions and encircling capillary loops and also in arteries
  2. proteinuria is a common manifestation and may result in nephrotic syndrome, often with a massive proteinuria
• structure- beta pleated sheets

• usually AL amyloid from Ig light chains produced by multiple myeloma or lymphoplasmacytic lymphoma

• post infectious glomerulonephritis
  • proliferative glomerulonephritis or post-streptococcal glomerulonephritis
• SLE
• Goodpastures syndrome

• decrease GFR
• salt and water retention
• often hematuria
• if sever, clinical picture of RPGN will develop

• epidemiology- most common cause of nephritic syndrome in children
• prognosis
  • majority of kids recover completely with biopsies only usually performed for persistent proteinuria
  • prognosis is not as good in adults (half recover)

1. requires previous infection on skin or throught with GAS
2. 1-2 weeks after untreated GAS infection develops, circulating Ag filtered by glomerulus become trapped
3. incites development of Ag-Ab complexes
4. incites inflammatory response in situ

• light microscopy
  • increase in number of cells in glomerulus
    • mainly neutrophils
    • sparing of tubulointerstitial compartment
  • inflammation cause swelling of glomerular tufts with disappearance of Bowman's space
• immunofluorescence
  • granular pattern of IgG and C3 deposition with deposits with variable size, randomly, and widely dispersed along capillary loops
• electron microscopy
  • few large, electron dense superficial depositis on epithelial cell side of BM (subendothelial humps)

• involve mesangium
• class I- lack light microscopy findings
• class II- include abnormalities in all three modalities

• class III: focal proliferative
• class IV: diffuse proliferative
• have endocapillary hypercellularity and usually crescents with large subendothelial immune complexes seen on LM, immunofluorescence, and ultrastructurally

• membranous nephritis
• demonstrates findings similar to membranous nephritis with the addition of mesangial deposits, which actually characterize all forms of lupus nephritis

• advancing sclerosis
• more than 90% global glomerulosclerosis
• immunofluorescent pattern for lupus nephritisof any type involves IgG, IgM, IgA with both complements (C3 and C1q)
  • "full house staining"
• distribution of deposits corresponds with class of lupus nephritis both on immunofluorescence and ultrastructurally

• anti glomerular BM Ab
• Ab's affect lung as well, leading to hemoptysis
• Ab's on kidney, which produce the clinical picture of RPGN
• similar to proliferative lupus nephritis or vasculitis associated glomerulonephritis by LM
• immunofluorescence
  • bright linear pattern of staining with IgG and C3