trans glomerularpatho final

8/14/2019 Trans Glomerularpatho Final

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Pathology of Glomerular Diseases

OS 214 Renal Dr. Teresita Tuazon

Exam # 1

March 3, 2009 | Tuesday Page 2 of 16

Canoy, Carasco, Cielo,

podocytes and vessels.

From Block B Trans:

Histologic Alterations

1. HYPERCELLULARITY

a. Cellular proliferation of mesangial or

endothelial cells

b. Leukocytic infiltration consisting of

neutrophils, monocytes andlymphocytes.

c. Formation of crescents.

Accumulations of cells composed ofproliferating parietal epithelial cells andinfiltrating leukocytes

Figure 6. Collapsed glomerular tuft. Note thecrescent-shaped mass (demarcated)

2. BASEMENT MEMBRANE THICKENING- Thickening of the capillary walls in light

microscopy

Figure 7. Thickened capillary wall pointed inarrow.

3. HYALINIZATION AND SCLEROSIS- Accumulation of homogenous and

eosinophilic material- Contributes to the obliteration of the

capillary lumina of the glomerular tuft

Figure 8. Collapsed capillaries, a feature ofsclerosis

Pathogenesis of Glomerular Injury

1. ANTIBODY MEDIATED

In situ Immune Complex formation

Deposition of circulating immune complexes

Antineutrophil cytoplasmic immune complexes

From Block B Trans:Complement Activation

Ag-Ab complexes may be intrinsic or extrinsic

Complexes can either be circulating in the

bloodstream or are in situ (extrinsic Ag depositedat the GBM and Ab complexes with it directly)

After some time, these complexes may causetissue lesions due to complement activationwhich elaborates other molecules and eventuallycause glomerular injury.

Figure 9.Circulating complexes


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Figure 13. Mediators of immune glomerular injury

including cells and soluble mediators

Glomerular Diseases

Asymptomatic proteinuria Nephrotic syndrome Asymptomatic hematuria Nephritic syndrome Rapidly progressive nephritic syndrome

Nephrotic Syndrome

Proteinuria greater than 3.5 gms/ 24 hours

(less in children) Hypoalbuminemia- plasma albuminless than 3 g/dL

Edema

Hyperlipidemia and lipiduria

The initial event is a derangement in glomerular

capillary walls resulting increased permeabilityto plasma proteins

Diseases frequently responsible for nephrotic

syndrome include (each will be discussedseparately in this trans):

o Minimal change disease

o Focal segmental glomerulosclerosis

o

Membranous glomerulopathy(idiopathic)

Figure 14. Primary nephrotic syndrome

From 2011 Trans:More stringent definition

Nephrotic range proteinuriao adults >3.0-3.5 grams/d

o children >40 mg/h

Clinical featureso Proteinuria

o Edema

o Hyperlipidemia

o Hypoalbuminemia

Hypercoagulableo urinary loss of anti-thrombin III and

plasminogeno hemoconcentration

Risk of Infections

Types Primary

o Membranous Glomerulopathy

o Focal Segmental Glomerulosclerosis

o Minimal Change Disease

o Membranoproliferative GN

Secondaryo Diabetic glomerulosclerosis

o Paraproteinemia/Amyloidosis

o Lupus Nephritis

Evaluation History and Physical Exam Urine Analysis Lab Studies Renal Biopsy

Table 1. Urine Sediment Types.

Nephritic Urine Nephrotic Urine Chronic GN

Red cells(hematuria)

Heavyproteinuria

Proteinuria

Variable proteinuria Free fat

droplets

Variable

hematuriaGranular casts Fatty casts Broad waxy

casts

Minimal Change Disease

Clinical Features

Most common features proteinuria and

periorbital edema, with or without othermanifestations of nephrotic syndrome

Most frequent cause of nephrotic syndrome in

childrenLight Microscopy

Minimal histologic changes Normal cellularity Proximal convoluted tubules with resorption

droplets Vessels and interstitium are unremarkable

Figure 15. Minimal Change Disease

In electron microscopy: in the visceral epithelial

cells


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o uniform and diffuse effacement of foot

processeso replaced by a rim of cytoplasm often

showing vacuolization, swelling andhyperplasia of villi

o fusion of foot processes/ effacement

> proteinuriao 85% responsive to steroids with reversal

of ultrastructural changes; overallprognosis good

Figure 16. Normal podocytes (individually sticking out)with slit pores. Endothelial layer has fenestrations >basement membrane

Figure 17. Fused podocytes in minimal change disease(white arrows)

In immunofluorescence microscopy:

o Negative immunofluorescence staining

within glomeruli no immunecomplexes

Figure 18. Immunofluorescence microscopy of MinimalChange Disease

Pathogenesis

Loss of polyanions and the glomerular charge-

barrier > loss of negative charge of BM

Primary visceral epithelial cell injury

Immune dysfunction leads to production of

cytokine-like circulating substance that affectsvisceral epithelial cells

Focal Segmental Glomerulosclerosis (FSGS)

Clinical Features Severe proteinuria or nephrotic syndrome- most

common manifestation Hematuria common, usually microscopic Hypertension common Male preponderance May be primary or secondary

Light Microscopy Some glomeruli (especially juxtamedullary ones)

with segmental sclerosis (mesangial matrixmaterial, collapse, basement membrane- likematerial , +/- hyalinosis

Figure 18. Focal collapse of glomerulus (encircled).

Figure 20. Hyalinosis in glomerulus


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Figure 21. Tubular atrophy normal glomerulus but with

thickened tubular walls, it could indicate presence of

FSGS even if glomerulus is normal as seen here.

Immunofluorescence Microscopy Usually normal except for sclerotic segment

which may have IgM, with or without C3

Figure 22. IF usually normal except for scleroticsegment which may have IgM, with or without C3.

Electron Microscopy and Course of Disease

uniform and diffuse effacement of foot processeson sclerotic and non-sclerotic areas plus

focal detachment of epithelial cells with

denudation of the underlying GBM

Accumulation in collapsed loops of matrix- like

material Course 15% responsive to steroids, over 1/3

progress to end stage renal disease

Figure 23. EM denuded BM, will progress to ESRD ->

dialysis, transplant. Accumulation in collapsed loops of

matrix like material

Pathogenesis initiating pathogenetic mechanisms are varied common element is injury manifested by

sclerosis in the setting of nephrotic rangeproteinuria.,

Degeneration and focal disruption of visceralepithelial cells

Hyalinosis and sclerosis represent entrapment

of plasma proteins in extremely hyperpermeablefoci with increased ECM deposition

Mutations in genes encoding for the proteins

nephrin and/or podocin causes increasedpermeability to proteins PROTEINURIA!

Primary/idiopathic FSGS

Secondary/variants FSGS

I.V. drugs

Collapsing gn: HIV, parvovirus B-19,

pamidronate, CS2, Loa Loa

Obesity-associated - reversible with weight

reduction

Familial FSGS - podocin, alpha-actinin-4

mutations

Congenital - Finnish type (nephrin mutation)

Cholesterol emboli

Lithium

Mitochondrial myopathies/cytopathies

Figure 24. FSGS survival rate


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Figure 25. Reductions in renal mass leading to focal

glomerulosclerosis which in turn leads to reductions in

renal mass creating a cycle

Does hyperfiltration injure the glomerulus?

Observations:

1. Subtotal nephrectomy (83%) in rats is followedby:

a. Increase blood flow and filtration perglomerulus

b. Proteinuriac. Focal glomerular sclerosisd. Progressive renal failure

2. High protein dietsa. Increase GFR and accelerate

glomerular sclerosis3. Low protein diets4. Similar lesions occur in some patients with

unilateral renal agenesis and in association withother diseases that reduce renal function mass

Membranous Glomerulonephropathy

Clinical Features

Proteinuria with or without the full nephrotic

syndrome - most common finding

Peak incidence in the fourth to fifth decades

Male preponderance

Most common cause of nephrotic syndrome inadults (remember minimal change disease most common cause of NS in children!)

Clinical Course

Spontaneous remission of proteinuria occur in

approximately of patients, approximately halfwill have stable renal function with or withoutcontinued proteinuria

Minority of patients will have slow decline in renal

function, a few will have rapid decline in renalfunction

1/3 progress, 1/3 remit, 1/3 protenuria only

In light microscopy:

Normal to extreme diffuse thickening of the

capillary wall

+/- tuft hypercellularity

foam cells in interstitium

In electron microscopy:

Numerous subepithelial deposits (+/-) spikes of

GBM in between

In immunofluorescence microscopy:

Finely granular diffuse capillary wall staining (-)

IgG, (+/-) C3 and other immunoreactants

Figure 26. LM:Hypercellularity of glomerular tuft

Figure 27. LM: silver staining BM spikes trying to cover

the deposits

Figure 28. IF: Finely granular diffuse capillary wall


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Figure 29. EM: Large subendothelial deposit (not just ahump)

Pathogenesis Believed to be chronic antigen-antibody mediated Genetic susceptibility Circulating immune complexes in 15-25% Direct action of C5b-9, the membrane attack

complex of complement in-situ immune complex formation in the

subepithelial zone Native or foreign antigens planted in the

glomerular basement membranes are presentbeforehand and antibodies to these antigenscombine with them in situ to form immune

complexes. presence of immune complexes alters the

permeability of the capillary loops leading toproteinuria.

Nephritic Syndrome

Hematuria Proteinuria Decreased glomerular filtration rate Elevated BUN and serum creatinine Oliguria Salt and water retention Edema

Hypertension

Glomerular Changes Leucocytic infiltration Hyperplasia of glomerular cells Necrosis (severe lesions) Injury to capillaries

Acute Glomerulonephritis

Clinical Features Also called poststreptococcal or postinfectious

glomerulonephritis Latent period between infection and onset of GN

( 1-2 wks for pharyngitis and 3-6 wks for skininfections )

Smoky urine and edema common initial manif,hypertension common, transient oliguria

Light microscopy Global and usually uniform hypercellularity Capillary lumina may be occluded Neutrophils frequent in the acute phase

( exudative glomerulonephritis)

Figure 30. LM: Uniformly and diffusely enlargedhypercellular glomeruli and reduced Bowman spaces

Immunofluorescence Microscopy Coarse granular staining in first few weeks for

IgG and C3 Later, predominant C3 and IgG scant to absent

Figure 31. IF: Variable-sized coarse granular deposits ofimmunoglobulins and complement in glomerular loops.

Electron Microscopy

Immune-type deposits on subepithelialsurface described as humps

Occasional patchy GBM thickening

Figure 32. EM: Variable-sized granular dense deposits ofIgG and C3 (humps) irregularly arrayed in thesubepithelial space of the glomeruli.

Pathogenesis


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Streptococcal antigens from the infection elicitthe production of anti-streptococcal antibodies.

Immune complexes form in situ in glomeruli due

to previously planted streptococcal antigens. The immune complex formation with complement

activation incites acute glomerular inflammation

Figure 33. Hypercellular glmeruli due to proliferation ofendothelial cells and mesangial cells, swelling ofendothelial cells, and inflammatory infiltrate (neutrophilsand monocytes). Initially, tubules are not affected (but asdisease progresses, they may present hydropic change).

Glomerulonephropathies Associated withIsolated Essential Hematuria

IgA Nephropathy ( Bergers Disease ) Thin Basement Membrane Disease Alports Disease Non-specific changes

IgA Nephropathy

Clinical Features Most common during the 2nd and 3rd decades Male preponderance Asymptomatic microhematuria to rapidly

progressive renal failure

5 to 15% have nephrotic syndrome

Light Microscopy Histologic Subclasses Type I Minimal histologic lesion

Type II- Focal segmental glomerulosclerosis-like

Type III Focal proliferative glomerulonephritis Type IV Diffuse proliferative GN Type V Advanced chronic GN

Figure 34. Glomerular tuft with global mesangialhypercellularity/proliferation. (Note that normal is lessthan or equal to 2 or 3 cells per mesangial area)

Figure 35. Red cell casts (arrows)

Immunofluorescence Microscopy

Mesangial granular IgA (in the absence of SLE,

HSP, active liver disease) Usually C1q is absent

Figure 36. IF: Granular deposits of IgA and C3 in theglomerular mesangium. The fundamental characteristic inIgA Nephropathy is the intense, diffuse mesangialimmunostaining for IgA that is limited to mesangial areas,

(without deposits in capillary walls). Diagnosis rests on thefinding of dominant IgA mesangial deposits. C3 is alsopresent in mesangial areas, but usually equal to or lessthan IgA staining.Electron Microscopy & Clinical Course

Mesangial electron dense deposits Variable clinical course and prognosis

Figure 37.

Pathogenesis


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presence of IgA immune complexes in theglomerular tufts

Presumably mucosal derived IgA combines withantigens to form circulating immune complexes

that deposit in the glomerular mesangium.,

Figure 38. EM: Electron-dense mesangial deposits andfoot process effacement.

Thin Basement Membrane Disease

thin GBM nephropathy is a genetically

heterogeneous disorder, with some but not allfamilial cases linked to mutations within thegenetic locus encoding the 3 and 4 chains oftype IV collagen (COL4A3/COL4A4 locus).

Figure 39. The main morphological feature in ThinBasement Membrane Disease (TBMD) is diffuse thinningof the GBM, particularly the lamina densa. Accuratemeasurement of the GBM thickness is therefore essentialin the diagnosis of TBMD.

Alport syndrome In Alport syndrome, type IV collagen, one of the

proteins that makes up the GBM, is absent orabnormal. Although the GBM looks normal inchildhood, it deteriorates with time because itlacks the special type IV collagen that should bethere

Alport syndrome is much more common in boys

and men because the gene that usually causes it(called COL4A5) is on the X chromosome.Women have two X chromosomes (XX), so theyusually have a normal copy as well as anabnormal copy of the gene

in less than 1 in 20 Alport transplants) kidneytransplants meet with a unique problem.

Because the transplanted kidney has normal type

IV collagen, the immune system may see it as'foreign' and attack it. This causes Alport anti-GBM disease, which is very similar to the kidneydisease seen in Goodpasture's disease.

Unfortunately it usually destroys the transplant.

Membranoproliferative Glomerulonephritis

Clinical Features Nephrotic syndrome common May have manifestations of the acute nephritic

syndrome such as hematuria, ( gross or microscopic), hypertension

MPGN Type ILight Microscopy

Proliferative, polymorphonuclears Lobulation/ tram-tracking

Figure 40. There is massive mesangial cell proliferation,mesangial matrix expansion and diffuse thickening andfocal splitting of the glomerular basement membrane.There is also accentuation of lobular architecture, swellingof cells lining peripheral capillaries, and influx ofleukocytes.Basement membrane thickening is due tomesangial cell and mesangial matrix interposition alongthe subendothelial side of the lamina densa withconsequent neoformation of basement membrane basically a doubling or complex replication of the BM thatgives the morphological aspect of double contour (tram-tracking). In other words, tram-tracking is caused by anincrease in mesangial cells and matrix in the capillaryloops, called mesangial interposition, which leads to newsubendothelial basement membrane deposition. The

mesangial matrix increase can be more severe inperipheral areas of the tuft, giving the glomerular tuft alobular appearance.

Figure 41. Increased mesangial matrix (stained black withsilver stain)

Immunofluorescence Microscopy Broad capillary wall deposits C3 +/- other things


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Figure 42. Immunofluorescence microscopy revealsgranular staining for the complement protein C3

Electron Microscopy

Interposition of mesangial cells and matrix

between GBM and capillary endotheliumaccounts for tram-track appearance

Subendothelial and mesangial deposit

Figure 43. EM: Subendothelial deposit incorporated intomesangial matrix (M).

Pathogenesis of MPGN I Immune complex mediated disorder.

IC are deposited in the mesangium and

subendothelial spaces.

Mesangial cells proliferate in response to the

immune complex deposition and extend beyondthe confines of the mesangium to mesangializethe capillary loops.

A second internal basement membrane is formed

by the mesangial cell and the underminedendothelial cells

Figure 44. Schematic representation of patterns in the twotypes of membranoproliferative GN. In type I there aresubendothelial deposits; type II is characterized byintramembranous dense deposits (dense-depositdisease). In both, mesangial interposition gives theappearance of split basement membranes when viewed inthe light microscope.

MPGN Type II/Dense Deposit Disease (DDD)

Light microscopy Any glomerular pattern (membranous,

membranoproliferative, normal, crescentic GN,etc.)

Figure 45.MPGN Type II Light Microscope.

Immunoflourescence Microscopy Broad capillary wall deposits C3 +/-, other

things, extraglomerular deposits

Notes from http://path.upmc.edu/cases/case148/dx.htmlMembranoproliferative glomerulonephritis type II (MPGN-II),also known as dense deposit disease (DDD), is aclinicopathologic entity associated with renal abnormalitieswhich often culminate in renal failure. DDD commonlyaffects children and young adults with a roughly equal maleto female preponderance. These patients present withvarying degrees of hematuria and/or proteinuria. In addition,serum analysis often but not invariably revealshypocomplementemia, particularly of the complementprotein C3, which has led some researchers to speculatethat abnormalities of the complement cascade contribute tothe pathogenesis of DDD.Distinguishing DDD from membranoproliferativeglomerulonephritis type I (MPGN-I) may be quite difficult

clinically since both are characterized by a nephrotic and/ornephritic clinical picture. However, microscopic examinationreveals differences that allow their separation. In MPGN-I,most glomeruli demonstrate global hypercellularity in alobular pattern. This differs from DDD in which a variety oflight microscopic patterns may be seen - includingmembranoproliferative glomerulonephritis (lobularglomerulonephritis), glomerular sclerosis, pure mesangialhypercellularity, membranous glomerulonephritis-likepattern, cresenteric glomerulonephritis, minimal changes, orfocal and segmental necrotizing glomerulonephritis.


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Figure 46. IF: Presence of the complement protein C3which produces a characteristic ribbon-like staining patternof the peripheral capillary loop; however, there is a lack ofstaining of the dense deposits.

Electron Microscopy Large electron dense deposits in GBM, +/-

TBM,BC,etc

Figure 47. Histologically, DDD is defined by the presenceof irregular electron dense deposits in the lamina densa ofthe glomerular basement membrane, which are observedby EM. These deposits are strongly PAS positive and aredark blue when stained with toluidine blue.

MPGN Types I & II Course and Diagnosis Course: Progressive (many to renal failure) Diagnosis: Low complement persistent, nephritic

and/ or nephrotic syndrome Autoimmune disorder C3 nephritic factor which is an IgG

immunoglobulin directed against C3 convertaseand on binding stabilizes it.

The stabilized C3 convertase continuously drivesthe alternative complement pathway, consumingcomplement.

As a consequence, patients have marked

hypocomplementemia.

Robbins book notesTypes I and II have altogether different ultrastructural andimmunofluorescent features.Type I MPGN (two thirds of cases) is characterized by thepresence of subendothelial electron-dense deposits.Mesangial and occasional subepithelial deposits may also bepresent. By immunofluorescence, C3 is deposited in a granularpattern, and IgG and early complement components (C1q andC4) are often also present, suggesting an immune complexpathogenesis.

In Type II MPGN lesions, the lamina densa of the GBM istransformed into an irregular, ribbon-like, extremely electron-dense structure because of the deposition of dense material ofunknown composition in the GBM proper, giving rise to theterm dense-deposit disease. In type II, C3 is present inirregular granular-linear foci in the basement membranes oneither side, but not within the dense deposits. C3 is alsopresent in the mesangium in characteristic circular aggregates(mesangial rings). IgG is usually absent, as are the early-acting complement components (C1q and C4).

PathophysiologyAlthough there are exceptions, most cases of type I MPGNpresent evidence of immune complexes in the glomerulus andactivation of both classic and alternative complementpathways. The antigens involved in idiopathic MPGN are

unknown. Conversely, most patients with dense-depositdisease (type II) have abnormalities that suggest activation ofthe alternative complement pathway. These patients have aconsistently decreased serum C3, but normal C1 and C4, theimmune complex-activated early components of complement.They also have diminished serum levels of factor B andproperdin, components of the alternative complement pathway.More than 70% of patients with dense-deposit disease have acirculating antibody termed C3 nephritic factor (C3NeF), whichis a conformational autoantibody that binds to the alternativeC3 convertase. Binding of the antibody stabilizes theconvertase, protecting it from enzymatic degradation and thusfavoring persistent C3 degradation and hypocomplementemia.There is also decreased C3 synthesis by the liver, furthercontributing to the profound hypocomplementemia.Precisely how C3NeF is related to glomerular injury and thenature of the dense deposits are unknown. C3NeF activity also

occurs in some patients with a genetically determined disease,partial lipodystrophy, some of whom develop type II MPGN.

Clinical PresentationThe principal mode of presentation is the nephroticsyndrome occurring in older children or young adults, butusually with nephritic component manifested by hematuria or,more insidiously, as mild proteinuria. Few remissions occurspontaneously in either type, and the disease follows a slowlyprogressive but unremitting course. Some patients developnumerous crescents and a clinical picture of RPGN. About50% develop chronic renal failure within 10 years. Treatmentswith steroids, immunosuppressive agents, and antiplateletdrugs have not been proved to be materially effective. There isa high incidence of recurrence in transplant recipients,particularly in type II disease; dense deposits may recur in

90% of such patients, although renal failure in the allograft ismuch less common.

Secondary MPGN arises in the following settings:

Chronic immune complex disorders, such as SLE;hepatitis B infection; hepatitis C infection, usually withcryoglobulinemia; endocarditis; infectedventriculoatrial shunts; chronic visceral abscesses;

HIV infection; and schistosomiasis. Partial lipodystrophy associated with C3NeF (type 2)

Alpha1 -Antitrypsin deficiency Malignant diseases (chronic lymphocytic leukemia,

lymphoma, melanoma)

Hereditary complement deficiency states

Notes from http://path.upmc.edu/cases/case148/dx.htmlDistinguishing DDD from membranoproliferativeglomerulonephritis type I (MPGN-I) may be quite difficultclinically since both are characterized by a nephrotic and/ornephritic clinical picture. However, microscopic examinationreveals differences that allow their separation. In MPGN-I, mostglomeruli demonstrate global hypercellularity in a lobular pattern.This differs from DDD in which a variety of light microscopicpatterns may be seen, as mentioned above. The capillary walls

in the glomeruli are markedly thickened and show intensestaining with PAS in MPGN-I. Methenamine silver also stains theglomerular basement membrane of the thickened capillary loopsto reveal splitting or tram tracking similar to what is observed inDDD; however, the material deposited between the glomerularbasement membrane borders is nonargyrophilic and differentfrom the deposits in DDD. Tram tracking in MPGN-I is caused byan increase in mesangial cells and mesangial matrix in thecapillary loops, called 'mesangial interposition', which leads tonew subendothelial basement membrane deposition. Electronmicroscopic findings in MPGN-I show mesangial interposition,subendothelial immune deposits and a new layer ofsubendothelial basement membrane. Immunofluorescencemicroscopy reveals granular staining for the complement proteinC3 differs from the ribbony pattern seen in DDD. In addition,MPGN-I biopsies, unlike those of DDD, may show staining forcomplement proteins Clq, C4 and one or more immunoglobulins,particularly IgG and frequently IgM. MPGN-I has a recognized


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Figure 48.The alternative complement pathway. Note thatC3NeF, present in the serum of patients withmembranoproliferative glomerulonephritis, acts at the

same step as properdin, serving to stabilize the alternativepathway C3 convertase, thus enhancing C3 breakdownand causing hypocomplementemia.

MPGN Type III with prominent subepithelial electron dense

deposits (Burkholder) with complex disruptions of the basement

membrane (Strife & Anders), focal and segmentalgloerular hyalin deposits, and infiltration by foamymacrophages

Acute Renal Failure Creatinine increases rapidly over a few days Oliguria/anuria frequent Etiologies:

Pre-renal

Renal

Post-renal

Crescentic Glomerulonephritis/Rapidly ProgressiveGlomerulonephritis (RPGN)

Clinical Features Clinical onset of disease usually abrupt Severe oliguria or anuria common at initial

examination Course is aggressive if without treatment

Table 1. Three Types of RPGN Based onImmunofluorescence Pattern

Robbins book notesRare variants (type III) segregated because they exhibit bothsubendothelial and subepithelial deposits are associated with

GBM disruption and reduplication.

Robbins book notesAcute renal failure is dominated by oliguria or anuria (no urineflow), with recent onset of azotemia*. It can result fromglomerular (e.g., crescentic glomerulonephritis), interstitial, andvascular injury or acute tubular necrosis.*Azotemia is a biochemical abnormality that refers to an

elevation of the blood urea nitrogen (BUN) and creatininelevels and is related largely to a decreased glomerular filtrationrate (GFR). Azotemia is produced by many renal disorders, butit also arises from extrarenal disorders. Prerenal azotemia isencountered when there is hypoperfusion of the kidneys (e.g.,in hemorrhage, shock, volume depletion, and congestive heartfailure) that impairs renal function in the absence ofarench mal dama e.

Robbins book notesRapidly progressive glomerulonephritis (RPGN) is a syndromeassociated with severe glomerular injury and does not denote aspecific etiologic form of glomerulonephritis. It is characterizedclinically by rapid and progressive loss of renal functionassociated with severe oliguria and (if untreated) death fromrenal failure within weeks to months. Regardless of the cause,the histologic picture is characterized by the presence ofcrescents in most of the glomeruli (crescenticglomerulonephritis). These are produced in part by proliferationof the parietal epithelial cells and Bowman capsule and in partby infiltration of monocytes and macrophages.RPGN may be caused by a number of different diseases, some

restricted to the kidney and others systemic. Although no singlemechanism can explain all cases, there is little doubt that inmost cases the glomerular injury is immunologically mediated.Thus, a practical classification divides RPGN into three groupson the basis of immunologic findings. In each group, thedisease may be associated with a known disorder or it may beidiopathic.

Notes from http://path.upmc.edu/cases/case148/dx.htmlCrescentic glomerulonephritis or rapidly progressiveglomerulonephritis (RPGN) is a term given to a diverse group ofdiseases which all have cresents present within the glomerulartuft. These include primary or renal limited (so-called idiopathic)crescentic glomerulonephritis, anti-glomerular basmentmembrane (anti-GBM) antibody diseases, and systemicdisorders. Considered within the entire clinical spectrum of

renal disease, RPGN produces the most rapidly progressiveand destructive of glomerular diseases which in the mostsevere forms proceeds inexorably to renal failure if not treatedaggressively and early. Fortunately, RPGN accounts for only 2to 7% of renal biopsies, with a disproportionately largepercentage of these patients progressing to end stage renaldisease.RPGN is categorized based on the biopsy immunofluorescencepattern into three groups: RPGN Type I (20%), RPGN Type II(40%), and RPGN Type III (40%) (Table 3). RPGN types I and IIhave greater than 2+ (on a 4+ scale) immunofluorescencestaining intensity with linear and granular staining patterns,respectively. RPGN Type III or pauci-immune type has weak orno demonstrable immunoglobulin / complement deposition,corresponding to an immunofluorescence staining intensity of

trans glomerularpatho final

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