Glomerular Disease

Question 1

Asymptomatic Hematuria (if it is glomerular in origin)

Answer 1

• dysmorphic RBCs (blebs or form casts)
• Can be first signs of:
  • Thin BM disease
  • IgA nephropathy
  • Alport (hereditary nephritis)

Question 2

Nephrotic Syndrome in General

Answer 2

• Proteinuria > 3.5 g/day (higher in kids)
• Hypoalbumin
• Hypogammaglobulin (inc infections)
• Hypercoaguable (liver makes more coag factors and lose anti-thrombin III)
• Hyperlipidemia and hypercholesterolemia (liver release more lipids and chol in response to dec protein in blood, dec LpL activity)
• Edema (low plasma oncotic p and Na/water retention)

Question 3

What is the general tx strategy for nephritic syndrome?

Answer 3

• Na restriction
• ACEi or ARBs
• Diuretics for edema
• Lipid lowering agents
• Treat based on specific cause

Question 4

Minimal Change Disease

Answer 4

• Associations = Hodgkin’s Lymphoma (cytokines –> damage podocytes)
  
  • • NSAIDs, mercury, lead, mono
• Demo = Kids
• Only lose albumin
• Normal LM/IF, just see podocyte fusion on EM
• Responds well to steroids

Question 5

FSGS

Answer 5

• Demo = Hispanic and black
• Associations = Heroine, HIV, sickle cell, obesity
• Familial version associated w/ APOL1 gene (podocyte proteins)
• LM shows focal and segmental hypercellularity (of glom and mesangial cells), hyaline lesion and segmental sclerosis
• EM shows effacement of podocytes and epithelial cells detaching from GBM
• Tx - may use cyclosporine, tacrolimus, mofetil

Question 6

Membranous Nephropathy

Answer 6

• Demo = Whites
• Associations = Hep B, Hep C, NSAIDs, PCN, SLE, solid tumors, malaria, syphilis
• Sub-epithelial deposits –> podocytes lay down new BM –> spike and dome; then once deposits are absorbed –> just leaves thick BM or train tracks
• IF shows granular deposits along membrane (IgG and C3)
• 1/3 rule
• Tx - corticosteroids alternating w. alkylating agents; if fails then try cyclosporine and tarcolimus, maybe rituzimab

Question 7

Membranoproliferative GN (2 types)

Answer 7

(can be nephrotic or nephritic)

• Type 1 = sub-endo (more tram-track; Hep B and Hep C)
  - “Mesangiocapillary”
  - One specific type = cryoglobulinemia (cryoglobulin deposition seen on IF)
• Type 2 = w/in BM (C3 nephritic factor stabilizes C3 convertase)
  - “Dense Deposit Disease”

Question 8

Diabetes GN

Answer 8

• Glucose on BM –> leaky –> proteins in vessel wall –> hyaline arteriolosclerosis (esp in efferent) –> back press –> hyperfiltration
• PAS - lots of sugar deposition

1- Nodular Glomerulosclerosis - nodules in mesangial matrix (Kimmelsteil-Wilson lesions)

2- Diffuse Glomerulosclerosis - diffuse in mesangial matrix

• Tx - control glucose, control BP, stop smoking, protein restriction (hyperfiltration)

Question 9

Amyloidosis GN

Answer 9

• In mesangium (congo red stain - apple green w/ polarized light)
• Can be from systemic amyloidosis (amyloid AA) OR amyloid of immunoglobulin origin (amyloid AL - w/ mainly lambda light chains and fragments of Bence Jones proteins)

Question 10

Light Chain Deposition Disease

Answer 10

• Kappa chain deposits
• Distinguish from lambda amyloid b/c
  
  • Congo red NEGATIVE and PAS positive
  • Prefer GBM and mesangium to vessels
• Tx - prednisone but more prognosis –> renal failure

Question 11

Nephritic Syndrome in General

Answer 11

• Proteinuria < 3.5 g/day
• Glomerular inflammation and bleeding (RBC casts)
• Na retention –> edema (esp periorbital edema)
• Hypercellular glomeruli
• Associated w/ immune complex deposition (C5a –> neutrophils –> damage)
• May see hypo-complementemia b/c so much complement activation

Question 12

5 Types of GN w/ hypocomplement

Answer 12

• C - cryoglobulinemia
• O - atherOemboli
• M - membranoproliferative
• P - post infection
• S - SLE

Question 13

Post-Strep GN

Answer 13

• Group A beta-hemolytic strep infection of skin or pharynx w/ nephritogenic strain; antibodies bind ECM or antigen in glomerulus –> complement cascade, IL-6 and ICAM-1
• Sub-epithelial humps form 2-3 wks post-infection and normally go away on own
• Cola-colored urine
• ASO titers if throat; AHT or anti-DNAse B titers if skin

Question 14

How to use IF to determine cause of rapidly progressive GN

Answer 14

• Linear- goodpasture (anti-BM antibody)
• Granular - immune complex mediated; post strep OR diffuse proliferative (SLE) OR IgA nephropathy OR membranoproliferative OR cryoglobulin associated GN
• None/minimal - ANCA
  
  • C-ANCA - Wegener (nasal/sinus involvement)
  • P-ANCA - Churg Strauss (asthma, granulomas, eosinophils) or microscopic polyangitis

Question 15

IgA Nephropathy

Answer 15

(Berger Disease)

• Post mucosal infection
• IF - predominantly IgA
• LM - can be normal or have focal or diffuse hypercellularity or crescents
• EM - see subendothelial deposits
• No TX

Question 16

SLE GN

Answer 16

• Anti-ds DNA antibodies and ANA and hypocomplement
• Can present as nephrotic or nephritic
• 1- Mesangial - subendothelial (pre-formed immune complexes deposit here) **diffuse proliferative type
• 2- Membranous (in situ formation in BM –> subepithelial deposits) **membrano-proliferative type
• IF - often see “full house” (IgM, IgG, IgA and all complement)

Question 17

Alport Syndrome

Answer 17

• Familial; often X-linked (males > females); collagen IV –> thin/split BM on EM
• Ear and eye involvement (nerve deafness, cataracts, etc)
• IF: absence of staining when use antibody to alpha-5 type IV collagen as stain

Question 18

Pathology of Chronic Glomerularnephritis (5)

Answer 18

• Kidneys become small
• Less proteinuria
• RBCs and broad casts
• Uremic state
• HTN dominates the clinical picture