Question | Answer |
Glomerulopathies
General considerations | Altered structure and Fxn
Generally acquired |
Nature of disease involvement
Primary | Intrinsic kidney disease
Often immune-mediated
May be unknown etiology |
Nature of disease involvement
Secondary | Extrarenal disease involvement |
Nature of disease involvement
Hereditary | Rarely |
Clinical features | Nephritic
Nephrotic
Hematuria |
Pathogenesis | Mechanisms of antibody-mediated damage |
Morphologic Alterations
Altered cells of the glomerulus | Proliferation:
-Endothelial
-Epithelial
-Mesangial
Effactment of foot processes |
Morphologic Alterations
Altered GBM or ECM | Thickened GBM or ECM
Thinned GBM
Deposition of immune complexes |
Morphologic Alterations
Inflammatory cell infiltrates | Macrophages and leukocytes |
General pathologic features of nephrotic syndrome | Typically normal glomerular cellularity
Absence of inflammation |
Minimal Change Disease
(MCD)
Clinical | Most common form of nephrotic syndrome in kids (~90%)
~15% in adults
Tends to be fairly "albumin selective" proteinuria |
Minimal Change Disease
(MCD)
Morphology | LM: normal
IF: negative
EM: effacement of podocytes
no immune deposits |
Minimal Change Disease
(MCD)
Prognosis | Most experience remission with corticosteroid Tx
Very good responce in kids
Some relapse upon withdrawal of corticosteroids |
Minimal Change Disease
(MCD)
Important points | Child
proteinuria >3.5
LM & IF negative
EM: effacement of podocytes |
Membranous Glomerulopathy
Clinical | Most common cause of nephrotic syndrome in adults
Whites and Asians |
Membranous Glomerulopathy
Etiology | Idiopathic
Autoimmune? |
Membranous Glomerulopathy
Morphology | LM: thickened capillary walls
Silver stain can show spikes
IF: granular staining for IgG
Complement along capillary loops
EM: subepithelial immune deposits |
Membranous Glomerulopathy
Prognosis | ~25% progress to ESRD |
Membranous Glomerulopathy
Important Points | Adult: white, asian
S/Sx of nephrotic syndrome
IF: confluent granular staining (IgG C3)
EM: subepithelial deposits |
Focal Segmental Glomerulosclerosis
(FSGS) | Scarring of portion of some glomeruli
Heterogeneous group of dz
Primary and secondary (HIV) |
Focal Segmental Glomerulosclerosis
(FSGS)
Clinical | Insidious onset of asymptomatic proteinuria with frequent progression to nephrotic syndrome
Most common cause in African Americans |
Focal Segmental Glomerulosclerosis
(FSGS)
Morphologic | LM:↑ ECM, hyalinosis
Maybe confused with MCD on biopsy
IF: trapping Ig and C3 in sclerotic regions
(no immune complexes) |
Focal Segmental Glomerulosclerosis
(FSGS)
Morphologic (EM) | Diffuse effacement of podocytes
Loss of podocytes and collapse of capillaries with ↑ ECM |
Focal Segmental Glomerulosclerosis
(FSGS)
Prognosis | Depends on underlying cause
Corticosteroids and ACEI typically beneficial |
Focal Segmental Glomerulosclerosis
(FSGS)
Important points | African-American Adult
May progress rapidly to ESRD
LM: may be normal
Focal and segmental changes
EM: foot process effacement |
Diabetic Glomerulosclerosis
(DGS) | Associated with small vessel disease throughout the body |
Diabetic Glomerulosclerosis
(DGS)
Clinical | Seen in ~50% diabetic pts
Microalbuminuria
Progress to proteinuria and nephrotic syndrome |
Diabetic Glomerulosclerosis
(DGS)
Etiology | Generalized increase in BM material synthesis in the microvasculature |
Diabetic Glomerulosclerosis
(DGS)
Morphology | LM:
Diffuse thickening of BM region and proliferation and expansion of mesangium
**Kimmelstiel-Wilson nodules** PAS
No immune complexes |
Diabetic Glomerulosclerosis
(DGS)
Prognosis | ~30% develope ESRD
Leading cause in USA |
Diabetic Glomerulosclerosis
(DGS)
Important points | Adult
Hyperglycemia (diabetic features)
LM: nodular sclerosis of glomeruli, arteriolar sclerosis |
Amyloid Nephropathy
Clinical | Renal involvement typical in AA and AL forms of system amyloidosis
Nonselective proteinuria |
Amyloid Nephropathy
Etiology | AA amyloid: associated with chronic inflammatory process
AL amyloid: associated with plasma cell neoplasm derived from light chains
(Multiple myeloma) |
Amyloid Nephropathy
Morphologic | LM: Congo red stain: apple green birefringence with polarized light
No immune complex deposits |
Amyloid Nephropathy
Prognosis | Unless underlying process is addressed, many lead to renal failure |
Amyloid Nephropathy
Important points | Adult
Evidence of systemic amyloiosis
Multiple Myeloma
Congo red: brick red
Apple green bifringence with polarized light |
Nephritic Syndrome | Inflammatory disease
Associated with:
hematuria, azotamia, HTN, variable subnephrotic proteinuria & edema |
Consequences of glomerular inflammation | ↑ GBM permeability= proteinuria
Microscopic defects= hematuria
(RBC casts/dysmorphic RBCs)
↓ GFR
↓ Na filtration
Edema |
Most common causes of nephritic syndrome | Primary GN:
IgA nephritis
Secondary GN:
Post-streptococcal GN
Secondary GN:
Lupus nephritis |
Acute Post-Infectious GN
Clinical | One of most common pediatric
Dx based on rise in serum titers of Ab against strep |
Acute Post-Infectious GN
Etiology | Most often group a strep
Type III hypersensitivity rxn
2-4 weeks post-infxn |
Acute Post-Infectious GN
Morphology | LM: proliferative GN
IF: "lumpy-bumpy" IgG, C3 around capillaries & mesangium
EM: sub-epithelial humps |
Acute Post-Infectious GN
Prognosis | Majority improve to baseline within months
No need to intervene |
Acute Post-Infectious GN
Important points | Child
Hx of pharyngitis 2-4 wks prior
Hematuria, oliguria, HTN, edema, proteinuria, azotemia
LM: ↑ cellularity
EM: subepithelial humps |
Membranoproliferative GN
(MPGN) | Proliferation of glomerular cells
Alterations in GBM
Infiltration by WBCs
Primary (type I&II)
Secondary |
Type I MPGN
Clinical | Can occur at any age
Often in older children and younger adults
More prevalent in underdeveloped countries with chronic infxn
Low C3 |
Type I MPGN
Etiology | Immune complexes in mesangium and subendothelial cap. walls |
Type I MPGN
Morphology | Mesangial hypercellularity
Glomerular crescents
Silver stain showing "tram tracking"
EM: subendothelial and mesangial dense deposits |
Type I MPGN
Prognosis | Tx of underlying disease
~50% progress to ESRD |
Type II MPGN
Clinical | Rare, more pronounced hypocomplementemia
Worse prognosis |
Type II MPGN
Etiology | Extensive complement in GBM
NOT immune complex
Most pts have IgG autoantibodies
(C3 nephritic factor) |
Type II MPGN
Morphology | LM: less pronounced hypercelularity
IF&EM: "ribbon-like" zone of increase density |
Type II MPGN
Prognosis | Lack of effective Tx
Some pts develop crescents and picture of rapodly progressive GN
~50% develop CKD in 10 yrs
High recurrance within transplanted kidney |
Membranoproliferative GN
Important Points | Adolescent/young adult
S/Sx of nephritic
Chronic infxn, low C3
LM: tram-tracking
IF: ribbon-like
EM: subendthelial/mesangial depots |
Lupus Nephritis | Autoimmune
Nephritis is one of the more common features (70%)
Immune complexes in variety of places
Tx= immunosuppression |
Lupus Nephritis
Important Points | Woman/African-American
Nephritic syndrome
SLE
ANA+ w/anti-dsDNA ab's
LM: wire-loop thickening of GFB |
IgA Nephropathy
CLinical | Most common form of GN in the world
Young men
40% asymptomatic microhematuria
10% nephrotic syndrome
Slowly progressive course |
IgA Nephropathy
Etiology | IgA-dominant immune complexes
Symptoms initiated or exacerbation with respiratory or GI infxn |
IgA Nephropathy
Morphology | LM: diffuse mesangial prolideration
Crescent formation is rare
IF: mesangial staining for IgA |
IgA Nephropathy
Important Points | Young man
Hematuria, proteinuria, oliguria, azotemia
Hx of resp or GI infection
LM: mesangial prolif.
IF: IgA staining |
Anti-GBM GN | Goodpasture's Disease
-associated with pumonary hemorrhage |
Anti-GBM GN
Clinical | Rare but aggressive
10-20% of RPGN
Serum anti-GBM abs
-Tx high dose immunosuppressants |
Anti-GBM GN
Etiology | 2-3 days after URIs
Autoantibodies against type IV collagen
Antigenetic epitope may be present in pulmonary alveolar capillary BM |
Anti-GBM GN
Morphology | LM:crescents
IF: diffuse linear staining of GBM and IgG |
Rapidly Progressive GN
(Crescentic GN)
Clinical | No specific etiology
Severe injury with rapid and progressive renal dysfunction
Severe oliguria
Signs of nephritic syndrome
Ultimate fatality w/o intervention |
Rapidly Progressive GN
Morphology | Presence of cresents in most glomeruli
Proliferation of parietal epithelial cells |
Rapidly Progressive GN
Prognosis | Not good |
Hereditary Nephridites | Present with hematuria
Two types:
Thin basement membrane dz
Alport syndrome |
Hereditary Nephridites
Thin basement membrane disease | Most common of the hereditary
Asymptomatic
Mutations coding Type IV collagen
EM: uniform thinning of GBM
Generally benign |
Hereditary Nephridites
Alport syndrome
Clinical | Hematuria with progression to CRF
Nerve deafness, eye disorders |
Hereditary Nephridites
Alport syndrome
Etiology | Majority are X-linked
-Females limited to benign hematuria
-Defective assembly of Type IV collagen |
Hereditary Nephridites
Alport syndrome
Morphology | EM: alternating thinning and thickening of GBM |
Hereditary Nephridites
Thin BM disease
Important Points | Young person
Asymptomatic hematuria
EM: Uniform thinning of GBM |
Hereditary Nephridites
Alport syndrome
Important Points | Male:
Hematuria with pregression to renal impairment
Nerve deafness, cataracts
Fracturing of GBM
Female: Hematuria only |
Chronic Glomerulosclerosis (CGN)
Clinical | Progressive RF
Oliguria
Uremia
Anemia
HTN with cardiac and CNS effects |
Chronic Glomerulosclerosis (CGN)
Etiologies | Those who survive acute phase of RPGN develop CGN and CRF
DM (30%)
HTN
Primary glomerular dz
Systemic autoimmine dz |
Chronic glomerulosclerosis (CGN)
Morphologies | Shrunken kidney with diffuse granular cortical surface
Cortex thinned
LM: arteriolar sclerosis, tubular atrophy, renal osteodystrophy |