❖ Nephrotic syndrome ❖ Nephritic syndrome
• Hypoalbuminemia bGfRY• Hematuria/ Acanthocytes*
• Hyperlipidemia • HTN
• Hypogammaglobinemia • Edema
• Hypercoagulability • Oliguria/ Azotemia (high BUN&Crt)
• *Thorn like cytoplasmic projections
DPGN and MPGN can have both syndrome
Nephrotic Syndrome: No effacement of foot processes in membranous and amyloid
Minimal Change Disease (Lipid nephrosis)
o Most common Nephrotic Syndrome (Mainly albumin) in children
o Associated with recent infection and immunization
o Rarely associated with Hodgkin Lymphoma (cytokine mediated damage)
o Loss of anti-thrombin III—> renal vein thrombosis
o "Negative immunofluorescence"
o "Effacement or fusion of foot podocytes" →
o "Normal appearing glomeruli"(lipid may be seen in
PT cells)
o T cell–mediated injury to podocytes
o Production of a glomerular permeability factor and
podocyte foot process fusion and dec anionic
properties of GBM LOSS of -ve charge selective
albuminuria)
Membranous Nephropathy (adults)
o Primary: antibodies to Phospholipase A2 receptors (anti-PLA2R)
o Secondary: Infection (HCV, HBV, Syphilis) Autoimmune Disease (SLE) or solid tumors
*o Medications (NSAIDs, Penicillamine, Gold)
o Inc risk of thromboembolism (eg, DVT, renal vein thrombosis).
o "Diffusely thickened basement membrane and capillaries"
o "Spike and dome appearance of subepithelial deposits"
o Granular due to immune complex (IC)deposition
"IMA Proud member of the spike and dome club''
Membranous: it means thickening of basement membrane creating a dome and
its associated capillaries creating a spike
Membrane can thicken on his own or by external force(primary and secondary)
Minimal children
Membranous adults
Focuses of deposits (IgM C1 C3) Segmental sclerosis African Am and Hispanic
Diabetic USA high income
❖ Focal Segmental Glomerulosclerosis (slower onset)
o Most common Nephrotic Syndrome in African American and Hispanic populations
o Primary(idiopathic)
&o Secondary (Sickle CD, HIV, heroin use, obesity,
INF treatment, or congenital malformations)
o May progress to CKD
o "Hyalinosis and segmental sclerosis"
o "Effacement of foot podocytes"
o "Nonspecific lgM, C1, or C3 deposition in a
mesangial matrix" and often negative
Cycles of eating and use require
interference
Sickle
Obesity
Heroin and HIV
IFN ttt
Diabetic glomerulonephropathy
o Most common cause of ESRD in high income countries/USA
o Usually associated with other evidence of diabetic complications (retinopathy,
neuropathy, gastropathy)
o ACEIs and ARBs are renoprotective
o Nonenzymatic glycosylation of the vascular basement membrane leads to
hyaline arteriosclerosis which causes hyperfiltration at the efferent arteriole and
subsequent microalbuminuria
o In other words (Hyperglycemia→ nonenzymatic glycation of tissue Proteins
→mesangial expansion →GBM thickening and inc permeability.
o Hyperfiltration (glomerular HTN and inc GFR)→ glomerular hypertrophy and
o glomerular scarring (glomerulosclerosis)→further progression of nephropathy.
o Look for albuminuria with inc urine albumin-to-creatinine ratio.)
o Mesangial sclerosis & expansion and GBM hypertrophy (predominantly due to increased
mesangial matrix, segmental podocyte effacement)
o Kimmelsteil-Wilson lesions (Sclerotic, eosinophilic nodules with a central acellular region)
o Non-specific staining.Usually negative.
Amyloidosis (amyloid in mesangium)
o Systemic amyloidosis most commonly affects the kidney
o May be associated with TB, multiple myeloma, Rheumatoid arthritis and prolonged
*
dialysis.
o AA protein is associated with chronic inflamAAtion
o AL protein is associated with multipAL
myeloma (plasma cell dyscrasias)
o AL amyloidosis: may be positive for lambda
and kappa light chains
o AA amyloidosis: positive for AA protein
o Mesangial expansion by amyloid fibrils
Post strept
Rapidly progressive cresce
Diffusely proliferative
Nephritic syndrome Inflammation of glomeruli IgA nephropathy
Alport $
Poststreptococcal Glomerulonephritis (Type 3 HSR) Membranoproliferative
o Usually, children about 2-4 weeks after group A beta hemolytic strep infection
o Adults: Staphylococcus is additional causative agent
o Type Ill hypersensitivity reaction Antistreptococcal antibodies (ASO)
o Low Serum C3 levels
o "Enlarged, hypercellular glomeruli"
o "Lumpy bumpy/granular/starry sky appearance" due to IgG, IgM, and C3(alternative
pathway) deposition along GBM and mesangium
o "Subepithelial humps"
Rapidly Progressive Glomerulonephritis (crescentic) (Poor prognosis)
o Refers to rapid progression of kidney disease (days to weeks)
o Actually, comprised of various individual diseases which are diagnosed based on
immunofluorescence
o Includes: Goodpasture Syndrome "Linear"
o Granulomatosis with Polyangiitis "Negative" or "Pauci Immune"
o Microscopic Polyangiitis "Negative" or "Pauci Immune"
o Diffuse Proliferative Glomerulonephritis or PSGN (IC RPGN) "Granular"
o "Fibrin or macrophage based crescentic expansion"
o "Crescent formation in Bowman Space” crescents consist of fibrin and plasma proteins (eg,
C3b) with glomerular parietal cells,
monocytes, macrophages
o Crescent is 2 layers of proliferating cells
within bowman space
o Immune or inflammatory injury to glo
capillaries lead to disruption of GBM and
gaps in capillaries→ influx of coagulation
factors(fibrinogen) and inflammatory
cells(lymphocytes)→ + coagulation cascade
and deposition of fibrin &inflammatory cells
recruits fibroblasts and + parietal cell
proliferation→ crescents
o In a nutshell; hypercellularity, fibrosis and
irreversible injury.
o IgA nephropathy and HSP may lead to RPGN
Goodpasture Syndrome
o Type II HSR marked by anti-GBM and anti-
alveolar antibodies
o Affecting Type IV Collagen
o Symptoms: Kidney (hematuria) + Lung
(hemoptysis) involvement
Granulomatosis with Polyangiitis (Wegener's)
o Small and medium sized systemic vasculitis
o PR3-ANCA/c-ANCA
o Symptoms: Kidney (hematuria) + Lung (hemoptysis) + Nasal (Rhinosinusitis) involvement
*Eosinophilic granulomatosis with polyangiitis (Churg Strauss) small vs
o Granulomatous, necrotizing vasculitis with eosinophilia
o History of asthma, sinusitis skin
sin nodules peripheral neuropathy)
or *Microscopic Polyangiitis
o Small vessel necrotizing vasculitis
o Similar to Wegener's but NO nasopharyngeal involvement and NO granuloma formation
o Lung, kidney and skin (palpable purpura)
*Both p-ANCA/MPO-ANCA
Diffuse Proliferative Glomerulonephritis
o Associated with SLE(Lupus nephritis: IgE deposition in capillary wall→ poorer prognosis)
o Thickening of glomerular capillaries AKA “wire Loops"
o Granular immunofluorescence
o Subendothelial, sometimes subepithelial or intramembranous IgG-based ICs often with C3
deposition
o Lupus immune staining is full house "Diff-Lupus (Diff-loop-us)"
IgA Nephropathy (Berger Disease)
o Occurs concurrently with respiratory or GI
tract infections (days after infection)
o Think of this as the RENAL version of IgA
Vasculitis
o Normal C3 levels
o Inc Serum IgA levels
o Symptoms: Asymptomatic microhematuria
following GI/respiratory infections
o "Mesangial IgA-based IC deposition"
"Mesangial proliferation"
Alport Syndrome (X-linked dominant)
o Glomerular "splitting and thinning" due to Type IV Collagen defect
o Symptoms: Sensorineural deafness, Glomerulonephritis, Ant Lens dislocation/Retinopathy
o "Can't see, can't pee, can't hear thee"
o "Basket weave"
o "Alternating (irregular) thinning and thickening and longitudinal splitting of the GBM"
o
· Initially negative; Irregular deposits of IgG, IgM, and/or C3 may be observed later.
Membranoproliferative Glomerulonephritis-Granular
*o Associated with HCV and HBV (2ry causes of type I)
o Most likely Nephritic syndrome to co-exist with Nephrotic syndrome
o Type I: Immunoglobulin mediated Associated with SLE
o Type II: Complement mediated(C3 nephritic factor)
o Associated with IgG antibodies that stabilize C3 Convertase
(persistent complement activation) AKA, Dense Deposit
Disease
o BOTH types have low C3 complement, IVDA
o "Tram track appearance of GBM" "Thickening and splitting
of GBM"
o "Mesangial ingrowth with a glomerular double contour"
o Type I-Subendothelial IC deposits
o Type II-Intramembranous deposits, also called dense deposit
disease
"I get 2 MPG on the tram track"
MPG = Membranoproliferative Glomerulonephritis Tram Track = characteristic finding
Track = track marks on somebody who engages with IVDA 2= 2 Types of MPGN
