Glomerular Diseases

Check Table 20-2

Five major glomerular syndromes: (Table 20-3)
Nephritic syndrome, RPGN, Nephrotic syndrome, Chronic renal failure, Isolated urinary abnormalities
Main histologic alterations: (either one or more of four)
1. Hypercellularity: characterized by

a. cellular proliferation of mesangial cells;
b. leukocytic infiltration of NEU, mono or lymphocytes;
c. formation of crescents (proliferating parietal epith cells and infiltrating leukocytes)- usu. Follows immune/inflammatory
injury.
i. Fibrin: molecule that is thought to elicit crescentic response
2. Basement membrane thickening
a. Thickening of capillary walls
b. Best seen via PAS
c. 2 forms seen via EM:
i. Amorphous electron-dense material deposition (usu. Immune complexes) at endothelial or epithelial side of
basement membrane
ii. Thickening of basement membrane due to inc. synth of protein components
3. Hyalinosis or sclerosis
a. Hyalinosis: accumulation of homogenous and eosinophilic material by light microscopy
i. Made up of plasma proteins that transfer from circ into glomerular structures
ii. If extensive: contributes to obliteration of capillary lumens
iii. Usu consequence of endoth aor capillary wall injury
iv. Common feature of focal segmental glomerulosclerosis
b. Sclerosis: accumulation of extracellular collagenous matrix
i. Either at mesangial areas (diabetic glomerulosclerosis) or capillary loops, or both
! Histologic changes of primary glomerulopathies may be subdivided into:
1. Diffuse: all glomeruli
2. Global: involves entire glomeruli
3. Focal: proportion only of all glomeruli
4. Segmental: part of each glomeruli (either mesangial or capillary loop)

Pathogenesis of glomerular injury
! Most forms of primary glomerulopathy and many of secondary are due to immune mechanisms (Table 20-4)
Immune complex deposition involving intrinsic and in situ renal antigens
1. Heymann nephritis
o Induced by immunizing animals with antigen contained within preps of proximal tubular brush border--- development of
antibodies--- membranous nephropaty devevlops
o Numerous electron-dense deposits at subepithelial aspect of basement membrane
o Granular pattern of immune deposition, not linear
o Megalin- Heymann antigen in rats
2. Antibodies against planted antigens
o Antigens may localize in kidney by interaction with intrinsic components of glomerulus
o Planted antigens include: (cations that bind to anion components of glomerulus)
DNA; nucleosomes; other nuclear proteins; bacterial products; large aggregated proteins; immune complexes
themselves
3. Anti-GBM Antibody-Induced Glomerulonephritis
o Masugi/nephrotoxic nephritis: experimental counterpart (injecting rats with anti-rat kidney antibodies prepped in rabbits
by immunization with rat kidney tissue)
o Linear pattern of immune deposition (compare with Heymann)
o Goodpasture syndrome: simultaneous kidney and lung lesions (involves other basement membranes)
Related to component of noncollagenous domain NC1 of alpha3 chain of collagen type IV
Circulating Immune Complex Glomerulonephritis
Caused by trapping of circulating antigen-antibody complexes within glomeruli
Antibodies have no immunological specificity for glomerular constituents
Complexes localize within glomeruli because of physiochemical properties and hemodynamic factors peculiar to glomerulus
Antigens may be:
o Endogenous (SLE)
o Exogenous
Lesions usually exhibit:
o Leukocytic infiltration
o Prolif of mesangial and endothelial cells
EM:
o Immune complexes that appear as electron-dense deposits at: mesangium, bet. endothelial cells (subendothelial
deposits), and at GBM or bet. outer surface of GBM and podocytes (subepithelial deposits)
IF:
o Granular deposition
Antibodies to glomerular cells
Most cases of human GN are consequence of discrete immune complex deposits
Visualized by granular IF at basement membranes or mesangium
Major pathway of glomerular injury
Cell mediated immunity in GN
Clues:
o Presence of activated macrophages and T cells plus products in glomerulus
o Evidence of lymphocyte activation on exposure to antigen
o Abrogation of glomerular injury by lymphocyte depletion
o Induction of glomerular injury by transfer of T cells from nephritic animals to normal recipients
Activation of alternative complement pathway
Occurs in dense-deposit disease/membranoproliferative glomerulonephritis (MPGN type II)

Epithelial cell injury
Can be induced by:
o Antibodies to visc epith cell antigens
o Toxins: puromycin aminonucleoisde induced proteinuria
o Cytokines
o Other poorly characterized factors
Changes in visc epith cells:
o Effacement of foot processes
o Vacuolization, retraction and detachment of cells from GBM
Detachment of cells maybe caused by loss of adhesive interactions with BM--- protein leakage
o Functional (proteinuria)
Mediators of glomerular injury
Cells:
o Neu and mono infiltration by: (Neu release proteases--- GBM destruction; free radicals; arachidonic acid--- dec in GFR)
Complement activation
Chemotactic events
Fc-mediated adherence and activation
o Mac, T lymph and NK cells
r/t antibody and cell-mediated rxns
o Platelets
Eicosanoid release and growth factors contribute to manifestations
o Resident glomerular cells
Esp emsangial cells:
Produce ROS, cytokines, chemokines, growth factors, eicosanoids, NO, and endothelin
Soluble Mediators:
o Chemotactic complement components
C5-9: causes cell lysis and causes mesangial cells to produce oxidants, proteases and other mediators
May cause proteinuria too even with Neu absence
o Eicosanoids, NO, angiotensin and endothelin
o Cytokines (TNF and IL-1)
o Chemokines
o Coagulation system
Fibrin: frequently in glomeruli in GN
Leaks into bowmans space--- stimulus for parietal epith cell prolif (crescent formation)
Mediated by Mac procoagulant activity

Mechanisms of progression in glomerular diseases
! 30-50% reduction or destruction of functional nephrons: end-stage renal failure proceeds at constant rate
2 major histologic characteristics of progressive renal damge: Focal Segmental Glomerulosclerosis (discussed later) and Tubulointerstitial
fibrosis
Tubulointerstitial fibrosis:
Tubular damage + intersitital inflammation
! there is much better correlation in renal fxn decline with tubulointerstitial damage rather than with glomerular injury
! Proteinuria causes direct injury to and activation of tubular cells--- activated tubular cells--- expresses adhesion molecules---
elaborates pro-inflammatory cytokines, chemokines and growth factors--- interstitial fibrosis
Filtered proteins that may activate tubular cells:
o Cytokines, complement products, iron in transferrin, Ig, lipid moieties and modified plasma proteins

A. Nephritic syndrome
Characterized by glomerular inflammation
Presents with:
Hematuria
RBC casts
Azotemia
Oliguria
Mild-moderate HPN
Proteinuria and edema are common (not as severe as in nephrotic syndrome
Typically characteristic of: acute proliferative GN
Impt component of crescentic glomerulonephritis
a. Acute proliferative (poststrep, postinfxs) glomerulonephritis
Diffuse proliferation of glomerular cells + influx of leukocytes
Lesions typically caused by immune complexes
Exogenous: postinfectious GN
Endogenous: SLE
1. Poststreptococcal GN
a. Appears 1-4 weeks after strep infxn
b. Granular immune deposits
c. Several cationic antigens including nephritis-assoc strep plasmin receptor (NAPIr)
d. Strep pyogenic exotoxini B (SpeB) and zymogenic precursor (zSpeB)
e. Morphology:
i. Classic: enlarged hypercellular glomeruli
1. Hypercellularity caused by:
a. Leukocyte infil and both Neu and Mono
b. Endothelial and mesangial cell proliferation
c. Severe cases by crescent formation
ii. Swelling of endoth cells and combo of proliferation, swelling and leukocyte infil---
capillary lumens obliterated
iii. Interstitial edema and inflammation
iv. Tubules with red cell casts
f. IF:
i. Granular IgG, IgM and C3 deposits in mesangium
ii. Focal and sparse immune complex deposits
g. EM:
i. Deposits on epith side of membae with appearance of humps
ii. Subendothelial and intramembranous deposits commonly seen
2. Nonstreptococcal acute GN
a. Granular IF deposits
b. Subepithelial humps char of immune complex nephritis are present
B. Rapidly progressive (crescentic) glomerulonephritis
Rapid and progressive loss of renal fxn assoc with: severe oliguria and signs of nephritic syndrome
Most common histologic picture: presence of crescents in most of glomeruli
Classification and pathogenesis
o 1
st
type: Anti-GBM antibody-induced disease
Linear deposits of IgG and C3 in GBM
Goodpasture syndrome: (with lung involvement)
Responsive to plasmapheresis
o 2
nd
type: immune complex deposition
Complication of any of the complex nephritides (postinfectious glomerulonephritis, lupus nephritis, IgA
nephropathy and Henoch-Schonlein purpura)
Granular pattern
Cellular proliferation within glomerular tuft plus crescent formation
Nonresponsive to plasmapheresis
o 3
rd
type: pauci-immune type
Lack of anti-GBM antibodies or immune complex
Most have:
Antineutrophil cytoplasmic antibodies--- cytoplasmic or perinuclear staining patterns
Idiopathic: isolated pauci-immune crescentic GN
! ANCA: highly sensitive dx marker for pauci-immune crescentic GN
Common denominator of all three types: severe glomerular injury
Morphology:
o Enlarged, pale with petechial hemorrhages
o histologic
there were distinctive crescents
Fibrin strands again that are frequently prominent bet. cellular layer in the crescents
IF:
Granular immune deposits
Goodpasture: linear GBM fluorescence
Pauci-immune: little or no deposition
EM:
Ruptures in GBM
C. Nephrotic syndrome:
Pathophysiology:
o Manifestations:
Massive proteinuria (3.5g or more of protein)
Hypoalbuminemia (3gm/dL or less of plasma albumin levels)
Generalized edema
Hyperlipidemia and lipiduria
o Initial event: derangement in glomerular capillary walls--- inc. permeability to plasma prtoeins
o Heavy proteinuria--- serum albumin level depletion beyond compensatory synthetic capacity of liver--- hypoalbuminemia-
-- generalized edema
o Sodium and water retention--- aggravates edema
o ! Highly selective proteinuria: mainly low molecular weight proteins
o ! Poorly selective proteinuria: higher molecular weight globulins in addition to albumin
o Inc. synthesis of lipoproteins in liver; abn transport of circ lipid particles, dec catabolism--- hyperlipidemia--- lipiduria---
lipid either as free fat or oval fat bodies- represents lipoprotein resorbed by tubular epith then shed along with
degenerated cells
o Loss of immunoglobulins in urine--- prone to infxn
o Loss of endogenous anticoagulants and antiplasmins in urine--- thrombotic and thromboembolic complications
Causes:
o Children younger than 17: almost always due to lesion primary to kidney
o Adults: often assoc with systemic disease
o Check table 20-7
a. Membranous Nephropathy
o Characterized by: diffuse thickening of glomerular capillary wall r/t accumulation of Ig-containing deposits along
subepithelial side of basement membrane
o Occurs most notably with:
Drugs (penicillamine, captopril, gold, NSAIDs)
Underlying malignant tumors (esp lung, colon and melanoma)
SLE
Infxns (chronic Hep B, Hep C, syphilis, schisotosomiasis, malaria)
Other autoimmune d/o (thyroiditis etc)
o Pathogenesis:
Chronic immune complex-mediated dse by both exogenous and endogenous (both renal and nonrenal)
antigens
Lesions here bear striking resemblance to Heymann nephritis
Uniform presence of complement--- direct action of C5b-C9--- attacks membrane and activates glomerular
epith and mesangial cells--- protease and oxidant liberation--- capillary cell wall injury and inc protein leakage
o Morphology:
LM:
Normal in early stages
Exhibit uniform, diffuse thickening of glomerular capillary wall
EM:
Irreg dense deposits bet basement membrane and overlying epith cells (effaced foot processes)
Basement membrane material is laid down bet deposits--- irregular spikes best seen in silver stains--- thicken--
- domelike protrusions--- closes over immune deposits--- markedly thickened irregular membrane
IF:
Granular deposits of both Ig and complement
Sclerosis occurs as disease advances
b. Minimal-Change Disease
o Most frequent cause of nephrotic syndrome in children
o Char: Diffuse effacement of foot processes of visceral epith cells in glomeruli
o Normal looking in LM
o 2-6 yrs: peak
o Most characteristic feature: response to corticosteroid therapy
o Etiology and pathogenesis
Immunologic despite absence of immune deposits because of:
Association with respi infxns and prophylactic immunization
Response to corticosteroids/immunosuppression Rx
Assoc with other atopic d/o
Inc prevalence of certain HLA haplotypes assoc with atopy
Inc incidence with Hodgkins lymphoma
Proteinuria-inducing factors reported in plasma or lymphocyte supernatants of pxs with this dse
Current hypothesis: immune dysfxn--- elaboration of cytokine--- damage of visceral epith cells--- proteinuria
Probably also due to mutations in podocyte proteins (nephrin and podocin)
Nephrin gene mutation: hereditary form of congenital nephrotic syndrome (Finnish type)
o Morphology
LM:
Normal
EM:
GBM appears normal
No electon-dense material deposition
Principal lesion: at visceral epith cells: effacement of foot processes
Replacement of fot processes by rim of cytoplasm with vacuolization, swelling and hyperplasia of
villi
! Foot process effacement also present with other proteinuric states
o Only when assoc with normal glomeruli= Minimal change dse
! visc epith changes are completely reversible esp after corticosteroid Rx
IF:
No Ig or complement deposits
c. Focal segmental glomerulosclerosis
o Sclerosis of some glomeruli with only a portion of capillary tuft involved in affected glomeruli
o Classification and types:
Occurs in:
As primary disease: idiopathic
Assoc with: HIV, sickle cell dse, massive obesity
As secondary event:r/t scarring of previously active necrotizing lesions (IgA nephropathy)
Component of adaptive response to loss of renal tissue (renal ablation)
Idiopathic focal segmental glomerulosclerosis (10-35%)
Diff with minimal change dse:
Higher incidence of hematuria, reduced GFR, HPN
Nonselective proteinuria
Poor response to corticosteroid Rx
Progression to chronic kidney dse
o Pathogenesis:
Hallmark of FSGS: degeneration and focal disruption of visceral epith cells (accentuation of diffuse epith
change of MCD)
Hyalinosis and sclerosis: from entrapment of plasma proteins in hyperpermeable foci and inc ECM deposition
o Morphology:
LM:
Focal and segmental lesions involve only minority of glomeruli (may be missed if bx has insufficient
number of glomeruli)
Lesions usu involve juxtamedullary glomeruli
In sclerotic segments: capillary loop collapse, inc in matrix, segmental deposition of plasma
proteins on capillary wall (hyalinosis)
Lipid droplets and foam cells often present
Glomeruli usu appear normal, but may show inc mesangial matrix
EM:
Effacement of foot processes
Focal detachment of epith cells
Denudation of underlying GBM
IF:
IgM and C3 at sclerotic areas and/or in mesangium
Pronounced hyalinosis and thickening of afferent arterioles
o Collapsing glomerulopathy:
Morph variant of FSGS
Retraction and or collapse of entire glomerular tuft
Characteristic feature: prolif and hypertrophy of glomerular visceral epith cells
Idiopathic usu
Most characteristic lesion of HIV-assoc nephropathy
Assoc prominent tubular injury with microcyst formation
Poor prognosis
o HIV-Assoc nephropathy
Morphologic features:
High frequency of collapsing variant of FSGS
Focal cystic dilation of tubule segments (with proteinaceous material and inflamm and fibrosis)
Large numbers of tubuloreticular inclusions within endoth cells in EM (ER modfications induced by
IFN-alpha) ! not seen in idiopathic FSGS!
R/t infxn of glomerular and tubular cells by HIV
d. Membranoproliferative glomerulonephritis
o Characterized by: (typically in mesangium or sometimes in capillary loops--- hence term mesangiocapillary GN)
alterations in glomerular basement membrane
prolif of glomerular cells
leukocyte infil
o may present with hematuria and proteinuria (non-nephrotic range) or may be a combined nephrotic-nephritic picture
o may be idiopathic or secondary to other systemic d/o
o primary MPGN has 2 major types (type I and type II: dense-deposit disease)
o Pathogenesis
Type I
Immune complexes in glomerulus + activation of classical and alternative comp pathways
Generally due to unknown antigens
Type II
Activation of alternative complement pathway r/t dec C3, but normal C1 and C4
Factor B and properdin: diminished serum levels, but with deposition of these with C3 in glomeruli
Also dec. C3 synth by liver--- contributes to profound hypocomplementemia
o Morphology
LM:
Both type I and II are similar
Large and hypercellular glomeruli
o Prolif in mesangium and endocapillary prolif
Crescents are present in many cases
Lobar appearance of glomeruli r/t proliferations and inc mesangial matrix
Thick GBM often segmentally
Tram-track appearance esp in silver or PAS stains
o r/t duplication of basement membrane or splitting
o ! inclusion or interposition of cellular elements within duplicated membranes
Type I
EM:
o Discrete subendothelial electron dense deposits
o Mesangial and occasional subepith deposits may be present
IF:
o Granular pattern of C3 deposition
o IgG and early complement components (C1q and C4) often present--- suggests immune
complex pathogenesis
Type II
EM:
o Lamina densa of GBM transformed--- irregular ribbon-like electron-dense structure
Due to deposition of dense material of unknown composition at GBM proper
IF:
o C3 present in irregular granular or linear foci
At either side of basement membranes !! not within!!
o !! Absence of IgG and early complement components
o Secondary MPGN
Invariably type I and more common in adults
Arises from:
Chronic immune complex d/o (SLE, Hep B, Hep C infxn)
Alpha1-antitrypsin deficiency
Malignant dses (lymphoma and CLL)
Hereditary deficiencies
D. Isolated urinary abnormalities
a. IgA nephropathy (Berger dse)
IgA Deposits in mesangial regions by IF
Frequent cause of recurrent gross or microscopic hematuria
Most common type of GN worldwide rarely present
Similar IgA deposits are present in Henoch-Schoenlein purpura
Secondary IgA nephropathy occurs in pxs with liver and intestinal dses
Pathogenesis
Inc. plasma polymeric IgA
Only IgA1 (not IgA2) forms nephritogenic deposits
Prominent mesnangial deposition
Presence of C3 + absence of C1q and C4: suggests activation of alternative complement pathway
Genetic or acquired abnormality of immune regulation--- inc IgA synth in response to respi or GI exposure to
envtal agents
Occurs with inc frequency in individuals with gluten enteropathy/ celiac disease
Inc also in pxs with liver dse
IgA deposited is polyclonal
Morphology
LM:
o Normal glomeruli
o Mesangial widening or endocapillary prolif (mesangioproliferative GN)
May be result of cell prolif, matrix accum, immune deposits or combination
o S1egmental proliferation confined to some glomeruli (focal proliferative GN)
Healing of this lesion may lead to secondary focal segmental sclerosis
o Overt crescentic GN
IF:
o Mesangial deposition of IgA with C3 and properdin (lesser IgG or IgM)
o ! Early complement components are usually absent!
EM:
o Deposits in mesangium
Older children and young adults usually affected
b. Hereditary Nephritis
Alport syndrome
When fully developed:
o Hematuria with progression to CRF
o Nerve deafness, various eye d/o (lens dislocation, posterior cataracts and corneal dystrophy)
X-linked trait
o Males express full syndrome
o Females are carriers (manif limited to hematuria)
Autosomal recessive and dominant pedigrees also exist (M=F susceptibility)
Pathogenesis:
o Due to abnormal alpha3,4 or 5 type IV collagen--- defective function of GBM, lens of eye and
cochlea
o ! alpha 3 chain includes Goodpasture antigen--- glomeruli fom pxs with alport who lack alpha3
chain--- fail to reac to GBM antibodies from pxs with Goodpasture syndrome
Morphology:
o LM:
Glomeruli always involved
Early lesion: detectable only by EM (diffuse GBM thinning)
As dse progresses: devt of focal segmental and global glomerulosclerosis and other
changes of progressive renal injury (vasc sclerosis, tubular atrophy and interstitial
fibrosis)
o EM:
Irregular foci of thickening alternating with attenuation of GBM
Pronounced splitting and lamination of lamina densa--- basket weave
o Immunohistochemistry:
Helpful in cases with absent or borderline basement membrane lesions
! antibodies to alpha 3,4,5 collagen fail to stain glomerular and tubular basement
membranes in classic x-linked form!
Absence of alpha 5 staining in skin bx specimens too
Thin basement membrane lesion (Benign familial hematuria)
Manifested clinically by:
o Familial asymptomatic hematuria uncovered usu on routine urinalysis
o Morphologically diffufse thinning of GBM (400nm dec to 150-250nm)
o Renal fxn is normal
o No hearing loss, ocular abnormalities etc
o Mutations of alpha 3, or 4 chain genes
o Most are heterozygotes resembling autosomal recessive Alport syndrome
o Homozygotes or cpd hetero may progress to RF


E. Chronic glomerulonephritis
Pool of end-stage glomerular dse fed by several streams of specific types of GN (check Fig 20-21 for percentage chances of chronic
GN from various forms of GN)
Morphology
o Gross:
Symmetrically contracted with diffuse granular cortical surfaces
Section:
Cortex is thinned with inc in peripelvic fat
o LM:
Early: glomeruli still show evidence of primary dse
Eventually obliteration of glomeruli
Acellular eosiniophilic masses
o trapped plasma proteins
o inc mesangial matrix
o basement membrane-like material
o collagen
arterial and arteriolar sclerosis may be conspicuous
marked atrophy of assoc tubules
irreg interstitial fibrosis
mononuclear leukocytic infil
o Dialysis changes:
Arterial intimal thickening (accum of smooth muscle-like cells and loose proteoglycan-rich stroma)
Focal calicification (usu within residual tubular segment)
Extensive Ca oxalate deposition in tubules and interstitium
Acquired cystic dse
o Uremic complications: (usu extrarenal)
Uremic pericarditis
Uremic gastroenteritis
Secondary hyperparathyroidism with nephrocalcinosis and renal osteodystrophy
Left ventricular hypertrophy r/t HPN
Pulmonary changes of diffuse alveolar damage (uremic pneumonitis)
F. Glomerular lesions assoc with systemic diseases
1. Lupus nephritis
o Manifestations:
Recurrent microscopic or gross hematuria
Nephritic syndrome
Nephrotic syndrome
CRF
HPN
2. Henoch-Schoenlein purpura
o Manifestations:
Purpuric skin lesions involving extensor surfaces of arms and legs + buttocks
Abdominal manifestations (pain, vomiting, intestinal bleeding)
Non-migratory arthralgia
Renal abnormalities
Gross or microscopic hematuria
Nephritic and nephrotic syndrome or a combo
Small number: rapidly progressive GN
o Most common to children 3-8 yrs old, but also in adults
o Strong bg of atopy in pxs (1/3)
o Onset often follows URTI
o IgA deposition similar to Bergers
o Morphology:
LM:
Varies
o mild focal mesangial prolif
o diffuse mesangial prolif
o endocapillary to crescentic GN
IF:
IgA deposition, sometimes with IgG and C3 in mesangial region
Skin lesions:
Subepidermal hemorrhages and necrotizing vasculitis (IgA present in these vessels)
Vasculitis occurs in other organs but is rare in kidney
3. Bacterial Endocarditis-Associated GN
o Immune complex nephritis of bacterial antigen and antibody
o Hematuria of proteinuria of various degrees
o Acute nephritic presentation
o RPGN may occur in rare instances
o Milder forms: focal and segmental necrotizing GN
o Severe forms: diffuse proliferative GN, and RPGN
o IF and EM: glomerular immune deposits
4. Diabetic nephropathy
o Most common lesions involve the glomerulus and assoc clinically with 3 glomerular syndromes:
Non-nephrotic proteinuria
Nephrotic syndrome
CRF
o May also affect arterioles--- hyalinizing arteriolar sclerosis
o Increases susceptibility to pyelonephritis devt
o May cause papillary necrosis
o Morphologic changes: (identical in Type I and type II DM)
Capillary basement membrane thickening
Diffuse mesangial sclerosis
Nodular glomerulosclerosis
o Pathogenesis: (principal points)
Caused by metabolic defects
Causes alterations in GBM (inc collagen type IV and fibronectin + dec heparin sulfate + inc ROS)
Nonenzymatic glycosylation of proteins--- advanced glycosylation end products--- glomerulopathy
Hemodynamic changes
Early stages:
o Inc GFR
o Inc glomerular capillary pressure
o Glomerular hypertrophy
o Inc glomerular filtration area
Both metabolic and hemodynamic changes contribute to podocyte loss d/t apoptosis r/t metabolic
abnormalities and exposure to ROS, or detachment from basement membranes due to met and hemodynamic
changes
5. Amyloidosis
o d/t deposits of amyloid within glomeruli
o most common amyloid of kidney is of light chain (AL) or AA type
o typical congo red positive fibrillary amyloid deposits in mesangium and capillary walls
rarel localized to subepith space
o amyloid obliterates glomeruli completely
o deposition also in blood vessel was and kidney intersitium
o nephrotic syndrome--- glomeruli destruction--- death by uremia
o kidney size either normal or increased
6. Fibrillary GN and immunotactoid glomerulopathy
o Fibrillary GN
Characteristic fibrillar deposits in mesangium and glomerular capillary walls
Fibrils with 18-24 nm (compared to 10-12nm of amyloid)
Resembles amyloid fibrils but differ ultrastructurally and Congo red negative
LM:
Membranoproliferative or mesangioproliferative patterns
IF:
Selective deposition of polyclonal IgG (IgG4 subclass), C3, Ig light chains
Clinically:
Nephrotic syndrome
Hematuria
Progressive renal insufficiency
o Immunotactoid glomerulopathy
Rarer; microtubular deposits of 30-50nm width
Circulating paraproteins and/or monoclonal Ig deposition in glomeruli
7. Other systemic d/o
o Goodpasture syndrome, microscopic polyangiitis, Wegener granulomatosis
All three are histologically similar and principally characterized by glomerular necrosis and crescent formation
Early or mild forms: focal and segmental necrotizing GN
Hematuria with mild dec in GFR
Severe:
RPGN assoc
Extensive necrosis, fibrin deposition, and extensive formation of crescents
o Essential mixed cryoglobulinemia
Deposits of cryoglobulins (IgG-IgM complexes) induce:
Cutaneous vasculitis
Synovitis
Proliferative GN (typically MPGN)
Usu with Hep C infxn and assoc with MPGN type I
o Plasma cell dyscrasias (multiple myeloma and etc)
Amyloidosis (fibrils with monoclonal light chains
Deposition of monoclonal IgG or light chains in GBM
Nodlar glomerular lesions from deposition of nonfibrillar light chains
PAS positive mesangial nodules, lobular accentuation and mild mesangial hypercellularity
Usu present with:
Proteinuria
Nephrotic syndrome
HPN
Progressive azotemia