Membranoproliferatve glomerulonephritis
• Characterized histologically by alterations in the basement membrane, proliferation of
glomerular cells, and leukocyte infiltration mainly in the mesangium
• Two types MPGN Type I and II, on the basis of distinct ultrastructural, immunofluorescence, and pathologic findings
• Type I may be primary or secondary
• (Type II: dense ribbon-like membrane deposits on EM)
MPGN Type I
• Most cases in adults are secondary to an identifiable etiology:
– Hepatitis C
– Infective endocarditis
– Lupus
– Chronic indwelling catheters
– Cryoglobulinemia
– Must exclude these before dx primary idiopathic MPGN
Cryoglobulins - MPGN
• Ig complexes precipitating in vitro when cooled below body temperature.
• Cryoglobulinemic MPGN often appears identical to MPGN on LM, IF, and EM.
• Usually Hep C related, may be idiopathic
Diabetic Nephropathy
• Kidney disease resulting from diabetes, including effects on glomeruli, vessels and tubulo-interstitium
• A leading cause of end stage kidney disease
• Renal failure is 2nd only to MI as a cause of death in DM
• 30-40% of all diabetics develop clinical evidence of nephropathy
– 50:50 Type I:Type II in absolute terms
– (Kidney disease is more likely in Type I, but there are more Type II diabetics)
• Frequency of DN is influenced by genetics
– Native Americans, Hispanics, and African Americans with Type II DM have a greater chance of developing chronic kidney disease vs whites
Proteinuria occurs in 50% of diabetics (I&II),
• Earliest: microalbuminuria (30-300mg/day albumin) and increased GFR are important predictors of future overt diabetic nephropathy
• Overt proteinuria, usually discovered 12-22 years after onset , mild at first, then nephrotic
• Followed by progressive loss of GFR, leading to end stage failure within 5 years
• Without treatment, 80% of Type I and 20-40% of type II will develop overt nephropathy with macroalbuminuria, over 10-15 years
• Progression variable, but by 20 yr, >75% Type I and 20%Type II will progress to ESRD
DN arteriole hyalinosis
Pathogenesis of diabetic
glomerulosclerosis
•1. Metabolic defect (incl altered glycosylation)
– GBM thickening, increase mesangial matrix, loss
of podocytes
• 2. Hemodynamic changes
– Similar to adaptive responses in secondary FSGS:
increased GFR (hyperfiltration), increased
glomerular capillar pressures, glomerular
hypertrophy, also loss of podocytes
Summary of DN
Diabetic Nephropathy
• Thickened basement membranes
• Diffuse mesangial sclerosis
• Nodular glomerulosclerosis (KW disease)
• Global glomeruosclerosis
• Hyaline deposits
• “Capsular drops”
• “Fibrin caps”
• Hyalinizing arteriolar sclerosis
• Tubular atrophy and intersitial fibrosis
Renal Amyloidosis
• Proteinuria or nephrotic syndrome
• Renal insufficiency is common
Amyloid is a pathological proteinaceous substance that results
from abnormal folding of proteins
not a single disease-- generic term for a heterogeneous group
of diseases that have in common tissue deposits of
extracellular fibrillar proteins that aggerate to form a crossbeta-pleated sheets, stain positively for congo red (with
green birefringence), and form non-branching fibrils 7.5 - 10
nm on EM
Once deposited, amyloid encroaches upon adjacent cells and
disrupts function
Normally light chains are reabsorbed in the proximal tubule
With a plasma cell dyscrasia excess light chain reabsorptive
capacity is exceeded
light chains in urine: “Bence Jones proteins”
Light-chain cast nephropathy (myeloma kidney)
• Bence-Jones (light chain) proteinuria: the light chains may combine with Tamm-Horsfall
protein under acidic conditions to form large distinctive casts that obstruct the tubular
lumens and induce an inflammatory response
• Precipitated by: dehydration, hypercalcemia
• Casts: amorphous masses, fractures, may be laminated, filling/distending tubular lumens
• Inflammation: multinucleated giant cell macrophage response, granulomatous
see lecture for review slides at end
