Renal Pathology Flashcards
Hematuria
Blood in the urine
Can by glomerular (nephrologic), hallmark of nephritic syndrome
Or extraglomerular (urologic)
Nephritic Syndrome
Clinical entity, usually acute onset
- Hematuria w/ dysmorphic cells and RBC casts
- Some degree of oliguria and azotemia
- Hypertension
Acute Postinfectious Glomerulonephritis
Children: Acute Nephritic Syndrome (hematuria, edema, HTN, renal failure)
Adults: Acute Nephritic Syndrome may be less common
Acute Postinfectious Glomerulonephritis
Epidemiology
Typically in children 6-10 years
Rarer in adults
Sporadic or endemic
Acute Postinfectious Glomerulonephritis
Etiology
1-4 weeks after recovery from infection
Pharynx Group A-B-hemolytic Streptococcal infections (GABHS), nephritogenic, M protein virulence factor
Other infections (pneumo, staph, viral)
Skin (impetigo)
Acute Postinfectious Glomerulonephritis
Pathogenesis
Immune complexes form in circulation (antigen + igG)
Deposition of immune complexes in capillary wall of glomerulus
Complement is activated (C5a)
Neutrophils attracted, mediate damage
Endocapillary proliferation and structural damage
“Swiss cheese” appearance with hematuria
Immune complexes are also formed IN-SITU (SUBEPITHELIAL DEPOSITS OR HUMPS) Unique to this syndrome
Acute Postinfectious Glomerulonephritis
Histology
Endocapillary proliferation (hypercellular tuft, capillaries occluded) neutrophilic infiltration (tri-lobed cells) Immune complex deposits by immunofluorescence and electron microscopy
Acute Postinfectious Glomerulonephritis
Laboratory Tests
Tea-colored (smokey/coca cola) urine Hematuria, mild proteinuria ASO titer INC Complement levels DEC Biopsy only required if course is ATYPICAL
Acute Postinfectious Glomerulonephritis
Prognosis
Children TOTAL RECOVERY in >95%
Adults have slow progression to chronic glomerulonephritis (because not identified until they go into renal failure)
15-50% of adults develop ESRD
Small subset of children/adults may develop severe acute illness
Acute Postinfectious Glomerulonephritis
Treatment
Supportive
IgA Nephropathy (Berger Disease)
RECURRENT gross and microscopic hematuria
Episodes of gross hematuria w/in 1-2 days of nonspecific URI (or GI or UTI)
Painless hematuria following infection
Hematuria for days, recurrence every few months
Henoch-Schoenlein purpura (main in children, small vessel vasculitis, purpura on skin, GI)
IgA Nephropathy (Berger Disease) Epidemiology
IgA nephropathy = most common glomerular disease worldwide
In children and young adults
IgA Nephropathy (Berger Disease) Etiology
Mucosal (respiratory, GI from food/bacteria) infection leads to IgA production
IgA immune complexes form and deposit in mesangium
Genetic or acquired abnormality in immune regulation
Abnormality in clearance of IgA
Antibodies against abnormally glycoslyated IgA
Activation of complement via alternative (rather than classic) pathway
IgA Nephropathy (Berger Disease) Histology
Mesangial proliferation (big spots on immunofluorescence)
IgA-complex in mesangium
Electron dense deposits by electron microscopy
IgA Nephropathy (Berger Disease) Laboratory Tests
Hematuria
Mild proteinuria
Complement levels NORMAL (liver is able to keep up with complement consumption)
Usually need biopsy for diagnosis/prognosis (see how much glomerulus is involved)
IgA Nephropathy (Berger Disease) Prognosis
Variable -> dependent on glomerular pathology
If prolonged can lead to renal failure
Small proportion of patients get aggressive course
IgA Nephropathy (Berger Disease) Treatment
Supportive
Hereditary Nephritis
Group of inherited glomerular diseases
MUTATIONS in glomerular basement membrane proteins
Structural alteration, error in synthesis of IV collagen (kidney, lens, cochlea)
Alport Syndrome
- nephritis
- nerve deafness
-various eye disorders, early cataracts
Hereditary Nephritis
Typical Clinical Presentation
Hearing and ocular abnormalities
Isolated hematuria
Hereditary Nephritis
Epidemiology
Age 5-20 at presentation
20-50 years with overt renal failure
Hereditary Nephritis
Etiology
X-linked inheritance
(+) family history
Male pts: full spectrum
Female pts: carries, rare with disease (X-chromosome inactivation)
Hereditary Nephritis
Pathology
Lamina dense splitting and lamination
“Basket weave”
Is not 3 distanct layers anymore
Hereditary Nephritis
Histology
Normal in parrafin sections
NO IMMUNE COMPLEX ( - immunofluoroscopy)
Electron microscopy is diagnostic (basket weave)
Hereditary Nephritis
Laboratory tests
Hematuria
Genetic Testing
Hereditary Nephritis
Prognosis
Overt renal failure between 20-50 years of age
Hereditary Nephritis
Treatment
Supportive
Transplantation
Counseling
Family Testing (prenatal testing is available)
Rapidly progressive glomerulonephritis (RPGN)
Rapidly progressive loss of renal function
Nephritis syndrome, gross hematuria
Cresents
Glomerular cresent
Glomerulus turns into a cresent shape Stops bleeding but compressed tuft Decreases filtration Rapid progression to renal failure If there is severe glomerular basement membrane injury, blood and FIBRIN and MACROPHAGES leak into Bowman space, parietal epithelial cells proliferate
Causes of cresents
Anti-glomerular basement antibody (RPGN type I)
Some circulating immune complex glomerulonephritis (RPGN type II)
Pauci-immune/ANCA associated (RPGN type III)
Rapidly progressive glomerulonephritis (RPGN) Type I
Gross hematuria
Drop in urinary output (acute renal failure)
Hemoptysis (small capillaries in lung are involved as well)
KIDNEY AND LUNG
Rapidly progressive glomerulonephritis (RPGN) Type I
Epidemiology
Young men
Rare
12% of cresentic glomerulonephritis
Rapidly progressive glomerulonephritis (RPGN) Type I
Etiology
Anti-glomerular basement membrane antibodies
Exposure of basement membrane: viruses, smoking, solvents (paints, dyes), drugs, industrial exposure
Genetic predisposition to autoimmunity
Rapidly progressive glomerulonephritis (RPGN) Type I
Histology
Immunofluorescence: Antibody deposited along entire length of glomerular basement membrane
Membrane destroyed, multiple areas of necrosis (GROSS HEMATURIA)
Goodpasture Syndrome
Antibody cross-reactivity with pulmonary alveolar basement membrane
Linear IgG deposits along glomerular and alveolar basement membranes
Antigen: noncollagenous protein (NC1)
Rapidly progressive glomerulonephritis and hematuria and pulmonary hemorrhage (hemoptysis)
Rapidly progressive glomerulonephritis (RPGN) Type I
Pathology
Crescents
Linear stain for IgG (not seen by electron microscopy)
IgG in glomeruli/pulmonary alveoli
Rapidly progressive glomerulonephritis (RPGN) Type I
Laboratory tests
Anti-glomerular basement membrane antibodies in serum
Levels may be low in rapid binding on kidney
Rapidly progressive glomerulonephritis (RPGN) Type I
Prognosis
Renal failure
Pulmonary failure
Rapidly progressive glomerulonephritis (RPGN) Type I
Treatment
Plasmapharesis
Removal of pathogenic antibodies from the circulation
Rapidly progressive glomerulonephritis (RPGN) Type II
Clinical Presentation
Gross hematuria
Drop in urinary output (acute renal failure)
Rapidly progressive glomerulonephritis (RPGN) Type II
Epidemiology
Rare
1% of postinfectious, small subset of IgA
Systemic lupus erythematosus (SLE)
Children, young adults (10-40 yo)
Rapidly progressive glomerulonephritis (RPGN) Type II
Etiology
Severe immune complex formation with necrosis
Breaks in glomerular basement membrane
Rapidly progressive glomerulonephritis (RPGN) Type II
Pathology
Crescents
Immune complexes (IgG+C3; IgA+C3)
Electron dense deposits by electron microscopy
Rapidly progressive glomerulonephritis (RPGN) Type II
Laboratory tests
Depends on etiology (ie postinfectious, IgA nephropathy, diffuse proliferative lupus)
Postinfectious: complement drop and ASO titers
IgA: no complement drop
SLE: no complement drop
Biopsy needs to be done because presentation clinical picture is not specific enough
Rapidly progressive glomerulonephritis (RPGN) Type II
Prognosis
Chronic renal failure
Rapidly progressive glomerulonephritis (RPGN) Type II
Treatment
Immunosuppression
Rapidly progressive glomerulonephritis (RPGN) Type III
ELK (eyes/ears/nose, lungs, kidneys)
Drop in urinary output (acute renal failure)
Gross hematuria
Hemoptysis, SOB
Rapidly progressive glomerulonephritis (RPGN) Type III
Epidemiology
Older patients
Rapidly progressive glomerulonephritis (RPGN) Type III
Etiology/pathogenesis
Antineutrophil cytoplasmic autoantibodies (ANCA)
ANCAs react w/neutrophils causing early degranulation and release of lytic enzymes
ANCAs are present in serum
DO NOT form circulating immune complexes
Direct cause of pauci-immune crescentic glomerulonephritis/systemic vasculitis
Rapidly progressive glomerulonephritis (RPGN) Type III
Laboratory Tests
Immunofluorescence on neutrophils: the ANCA shows up
ANCA: test for their presence
Rapidly progressive glomerulonephritis (RPGN) Type III
Pathology
Crescents
Extraglomerular vasculitis
NO immune complex deposits
NO electron dense deposity
NO anti-glomerular basement membrane autoantibodies
Immunofluorescence: negative (pauci immune)
Electron microscopy: negative (pauci immune)
In routine studies we don’t see the offending body, because there are no complexes deposited in kidney
Rapidly progressive glomerulonephritis (RPGN) Type III
Prognosis
Renal failure
Pulmonary
Rapidly progressive glomerulonephritis (RPGN) Type III
Treatment
Immunosuppression
Rapidly progressive glomerulonephritis (RPGN) Type III
Wegener granulomatosis
Vasculitis with necrosis and granuloma-like pathology
c-ANCA
Ear/nose/throat
Lung
Kidney
(remember Goodpasture is just lung/kidney)
Churg-Strauss Snydrome
Allergic granulomatosis and angiitis Small vessel necrotizing vasculitis with eosinophils Asthma, alleric rhinitis Lung infiltrates Peripheral eosinophilia Extravascular necrotizing granulomas Palpable purpura GI bleeding Renal disease myocardial infiltrates p-ANCA
Recap:
Type I RPGN
Anti glomerular basement membrane autoantibodies
Children
Goodpasture
Antibody against collagen in glomerular and alveolar basement membrane
Hematuria + hemoptysis
Young adult male
Recap:
Type II RPGN
Circulating immune complex Young adults Post-strep, diffuse proliferative glomerulonephritis Diffuse immune complex deposition Usually subendothelial Most common in lupus
Recap:
Type III RPGN
Pauci immune/ANCA Elderly Wegener granulomatosis (c-ANCA) Microscopic angiitis (p-ANCA) Churg-Strauss (p-ANCA) Eosinophils and asthma in Churg-Strauss
Nephrotic Syndrome
Increased permeability to plasma proteins
Membrane becomes more porous to proteins (not RBCs)
Massive proteinuria > 3.5 g daily
Hypoalbuminemia
Membranous Nephropathy
Clinical Presentation
Edema (looks like CHF in elderly)
Thrombosis (loss of ATIII)
Infections
10% in SLE pts
Membranous Nephropathy
Epidemiology
Young/middle age adults between 30 and 60
30% adults, second most common nephrotic syndrome
5% in children
85% autoimmune (idiopathic), 15% secondary
Membranous Nephropathy
Etiology
In-situ subepithelial immune complex formation
Autoimmune response against renal antigen
Carcinomas (lung, colon, breast, kidney), leukemia, non-Hodgkin’s lymphoma
Infections: malaria, hep B and C, congenital syphilis, leprosy
Drugs: penicillamine, gold
Membranous Nephropathy
Pathogenesis
In-situ immune complex formation Antibody against glomerular antigens IgG + complement granular deposits Rxn on basal surface of podocytes Injury to podocytes, loss of slit diaphragms Foot process effacement NO cellular rxn (no proliferation/WBCs) NO INFLAMMATORY RESPONSE
Membranous Nephropathy
Histology
No inflammation, no proliferation
Electron microscopy: subepithelial deposits
Immunofluorescence: granular deposits of IgG and C3
Silver stain: spike and dome (immune complex deposits are silver negative, basement membrane is black)
Capillary wall looks thickened and stiffer
Membranous Nephropathy
Laboratory Tests
Nephrotic snydrome (hypoalmbuminemia, hyperlipidemia, lipiduria)
Secondary hyperlimidemia, inc in total cholesterol
Inc in LDL, cholesterol
Accelerated atherogenesis
NO COMPLEMENT DROP (bc chronic and slowly progressing)
Antibody testing for PLA2R
NEED TO BIOPSY, clinical presentation is too vague
Membranous Nephropathy
Prognosis
1/3 pts will have spontaneous remission
1/3 progress to require dialysis
1/3 continue to have proteinuria, without progression to renal failure
Membranous Nephropathy
Treatment
Difficult Immunosuppressive drugs (Prednisone) Non-specific anti-proteinuric Secondary: Tx of underlying disease Recurrence after transplantation
Minimal Change Disease
Clinical Presentation
Edema (periorbital, generalized)
Minimal Change Disease
Epidemiology
Children 2-6 yo
65% of nephrotic syndrome in children
NO BIOPSY IF UNCOMPLICATED in course
Adults, 10% nephrotic syndrome in adults, need biopsy
Minimal Change Disease
Etiology
REVERSIBLE podocytes injury
T cell derived, ?cytokines
Dpression of immunity (viral infections, Hodkin disease)
NSAIDs
Minimal Change Disease
Pathology
No inflammation/cellular proliferation No immune complex deposits Effacement (fusion) of foot processes Membrane becomes thicker but more permeable Reversible (with steroids
Minimal Change Disease
Histology
Normal paraffin sections
No immune complex deposits
Foot processes effacement via electron microscopy
Minimal Change Disease
Laboratory Tests
Nephrotic Syndrome
Minimal Change Disease
Prognosis
Several episodes of nephrotic syndrome (relapses)
Normal renal function
Resolution at puberty
Minimal Change Disease
Treatment
Steroids
Focal and Segmental Glomerular Sclerosis (FSGS)
Clinical Presentation
Nephrotic syndrome Higher incidence of hematuria Reduced GFR HTN Non-selective proteinuria (albumin only)
Focal and Segmental Glomerular Sclerosis (FSGS)
Epidemiology
Adults 35%, most frequent pathology in human biopsy
Children 10%, older children
African American
Hispanic
Focal and Segmental Glomerular Sclerosis (FSGS)
Etiology
IRREVERSIBLE injury to podocytes
Focal and Segmental Glomerular Sclerosis (FSGS)
Histology
Some normal glomeruli
Some focal (segmental) obliteration (sclerosis) of glomerular capillaries
Collapse of capillary loops, increase in mesangial matrix
Immunofluorescence: negative
Electron microscopy: effacement of epithelial foot processes in ALL GLOMERULI
Focal and Segmental Glomerular Sclerosis (FSGS)
Progression
Initially only rare glomeruli involved (focal) Preferentially juxtamedullary glomeruli With progression more glomeruli involved Global sclerosis Tubular atrophy, interstitial fibrosis
Focal and Segmental Glomerular Sclerosis (FSGS)
Pathology
Segmental obliteration (sclerosis) of capillaries
Collapse of capillary loops
Inc. mesangial matrix
Initially only rare glomeruli involved (focal)
Focal and Segmental Glomerular Sclerosis (FSGS)
Laboratory Tests
Nephtrotic syndrome
Genetic testing
Focal and Segmental Glomerular Sclerosis (FSGS)
Prognosis
Progression to renal failure
Focal and Segmental Glomerular Sclerosis (FSGS)
Treatment
Initially steroid responsive
Progressively steroid dependent/resistant
Recurrence in transplants
Focal and Segmental Glomerular Sclerosis (FSGS)
Genetics
Inherited mutations in genes encoding slit diaphragm proteins
Genetic risk allels in APL1 in AA, adult-onset
Can be diagnosed in very young childnren
Focal and Segmental Glomerular Sclerosis (FSGS)
HIV varient
Collapse of tuft + proliferation of visceral epithelial cells
Normally podocytes cannot proliferate
HIV induces dedifferentiation, restores their ability to proliferate
Progression is rapid/dramatic, aggressive form
Morphology looks different
Wrinkled/collapsed
Membranoproliferative Glomerulonephritis (MPGN) Clinical Presentation
Nephrotic syndrome and hematuria
Membranoproliferative Glomerulonephritis (MPGN) Epidemiology
Older children (10%) Adults (10%)
Membranoproliferative Glomerulonephritis (MPGN) Etiology
Immune complex formation
Classical complex activation
Secondary: chronic autoimmune disorders, hepatitis, endocarditis, chronic bacterial infections
Monoclonal proteins (aka paraproteins) produced by clonal B cells/plasma
Membranoproliferative Glomerulonephritis (MPGN) Pathology
Thicken glomerular basement membrane
“Double contour”or “tram track” on silver stain
IgG + complement deposits, subendothelial
Increase in mesangial cells (chase immune complexes into walls)
Lobular tufts
Thicke glomerular basement
Membranoproliferative Glomerulonephritis (MPGN) Laboratory Tests
Low complement
Membranoproliferative Glomerulonephritis (MPGN) Prognosis
Progression to renal failure
Membranoproliferative Glomerulonephritis (MPGN) Treatment
Treat underlying disease (endocarditis, hepatitis, etc)
Dense Deposit Disease
Clinical Presentation
Nephrotic syndrome with hematuria
Dense Deposit Disease
Epidemiology
Rare
Older children
Dense Deposit Disease
Etiology
Sustained activation of complement via alternative pathway (non-antibody mediated)
No antigen-antibody formation
Dense Deposit Disease
Pathology
Complement (C3)
C3 convertase is usually digested quickly, but if something that prevents its removal the cascade keeps going
No immunoglobulin
Dense deposits within lamina densa (seen via electron microscopy)
Dense Deposit Disease
Laboratory Tests
Complement levels
Molecular studies
Dense Deposit Disease
Prognosis
Poor
Progression to renal failure
Recurrence in transplants
Dense Deposit Disease
Treatment
New therapies controlling complement activation
Diabetic nephropathy
Glomerular lesions
Diffuse and nodular glomerular sclerosis + nephritic syndrome
Atherosclerosis and arteriosclerosis
Pyelonephritis (acute & chronic)
Nonenzymatic glycosylation of vascular basement membrane resulting in hyaline arteriosclerosis
Amyloidoses
Deposits of anormally folded protein Congo red positive Plasma cell dyscrasia/multiple myeloma Kidney involvement: nephrotic syndrome FAT biopsy for screening! Tx depends on protein type Survival improves with early diagnsis
SLE
Systemic lupus erythematosus
Multisystem, renal involvement with edema
Primarily young women
Immune DNA-antiDNA complexes
Proliferative glomerulonephritis with necrosis and cresents
Nephritic syndrome
10% develop nephrotic syndrome
Do kidney biopsy for staging
Tests: autoantibodies, ANAs, anti-sm, anti-dsDNA
Ischemic ATI
Acute Tubule Injury
BP drop
Severe trauma
Acute pancreatitis
Toxic ATI
Acute Tubule Injury Drugs (antibiotics) Contrast dyes Poisons Organic solvents
Combine ATI
Acute Tubule Injury Ischemic + nephrotoxic Mismatched blood transfusion/other hemolytic crises (hemoglobinuria) Skeletal muscle injury (myoglobinuria) Intratubular casts Crystals Interstitial components
1st Degree Tubulo-interstitial Nephritis
Renal tubules and interstitium
Infections, acute and chronic
Drugs & toxins
Other (metabolic: urate, oxalate, hypercalcemia, neoplasm: multiple myeloma)
2nd Degree Tubulo-interstitial Nephritis
Associated with other diseases
Glomerulonephritis
Autoimmune
Acute Pyelonephritis
Bacterial infection (E. coli, proteus, klebsiella, enterobacter, streptococcus faecalis)
Also fungi and viruses
Can come via blood (hematogenous)
Or ASCENDING up the ureters
Acute- Drug Induced Interstitial Nephritis
Not Dose related
IgE mediate
+ skin test to drug hapten
Delayed hypersensitivity rxn (type IV)
NSAIDs Nephritis
Acute hypersensitivity interstitial nephritis
Nephrotic syndrome + renal failure
Looks like minimal change disease (foot processes effacement)
BUT WE START SEEING CREATINE IN URINE
Renal failure
Pronephros
4th week
Mesonephros
Caudally
Tubules degenerate
Duct persists
Mesonephric duct comes in contact with cloaca, grows cranially as ureteric bud
Renal Dysplasia
Aberrant nephronic differentiation
NOT NEOPLASIA
Presence of immature elements: undifferentiated mesenchyme, cartilage
Grossly enlarged kidneys, irregular shape (bunch of grapes)
Potter’s Sydrome
Fetal urine production is important for amniotic fluid development
Without amniotic fluid lungs develop poorly
Small, deformed, hypoplastic lungs
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Rare PKHD1 gene Enlarged kidneys Sponge-like appearance Dilated/elongated tubules Liver has cysts as well, fibrosis
Adult Polycystic Kidney Disease
Pain, colic, mass, hemorrhage, hematuria, renal failure, HTN Common Autosomal DOMINANT Cysts in kidney and liver Tx is transplantation Intracranial berry aneurysms Mitral valve prolapse
Aquired Cystic Disease
Dialysis associated
Cortical and medullary cysts
Renal cell carcinoma can occur
Benign Kidney Tumors
Oncocytoma (distal nephron, mahogeny brown with central scar)
Angiomyolipoma (vessels/smooth muscle/fat, huge/irregular vessels
Renal Cell Carcinoma
TRIAD: COSTO-VERTEBRAL PAIN, MASS, HEMATURIA
Incidentally discovered
Cause paraneoplastic syndromes (often how its discovered)
Found in the elderly
Very deadly
Can be sporadic or genetic
Kinda looks like adrenal gland
Extremely chemo-resistant, there are targeted therapies
von Hippel-Lindau (VHL) syndrome
Sutosomal dominant 37 years Multiple bilateral cysts and tumors, high vascularity Angiomas of retina Hemangioblastoma (CNS/cerebellum/spine) Pheos in some
Urothelial Carcinoma
Adults
Renal pelvis, ureter, frequently with bladder cancer
Hematuria
ANALGESIC NEPHROPATHY is a risk factor
Wilm’s tumor
25% have other developmental abnormalities
WAGR: Wilms tumor, Aniridia, Gu malformation, mental Retardation
Peds, most common kidney tumor
Malginant blastema (small blue cells, undifferentiated), tubules, stroma
Soft tumors, need to be careful when removing
Good prognosis
Very chemosensitive
