Glomerular Disease 1 Flashcards
what are the possible mechanisms of glomerular disease? (three)
• Immunocomplex deposition
– Circulate then deposit in glomerulus
• eg DNA-anti-DNA complexes in Lupus
– activates complement resulting in neutrophil chemotaxis
- Antibodies against GBM or glomerular antigens
- Cytokine production by inflammatory cells
circulating cause of glomerular disease
immune complex deposition
in situ cause of glomerular disease
anti-gbm, membranous: antibody against glomerular antigen
nomenclature of glomerular disease: possible types
diffuse, focal, global, segmental
how does glomerular disease present?
- loss of time (temporal change)
- hematuria (quality)
- proteinuria (quantity)
nephrotic syndrome characteristics
• Proteinuria > 3.5 g/day • Hypoalbuminemia • Edema – Loss of plasma oncotic pressure vs Na/H20 retention • Hyperlipidemia – increased hepatic protein production • Lipiduria • Hypercoagulability – loss of Proteins C & S
characteristics of nephritic syndrome
• Mild proteinuria • Hematuria – RBCs, RBC casts, dysmorphic RBCs • Hypertension • Edema
common characteristic for both nephrotic and nephritic syndromes
both may have varying degrees of renal dysfunction
causes of acute glomerularnephritis
– IgA nephropathy – Post-infectious GN – Anti-GBM disease/Goodpasture’s – Small vessel vasculitis – Lupus nephritis – Membranoproliferative GN
IgA nephropathy prevelance and age of onset
- Most common GN worldwide
* Most patients between age 10-50
features of IgA nephropathy
• Hematuria is most prominent feature
– 50-60% episodic gross hematuria
– 30% persistent microhematuria
– 10% acute GN or nephrotic syndrome
• Proteinuria, if present, is generally mild
• Many cases are subclinical
symptoms of IgA nephropathy
- Dysuria and loin pain may accompany hematuria
- Hematuria frequently occurs in conjunction with an upper respiratory infection (“synpharyngitic hematuria”)
- HTN may be present in patients with more advanced disease
IgA nephropathy histology features on LM
• LM: Variable mesangial hypercellularity (mesangial proliferation)
– May see segmental proliferation, segmental sclerosis and necrosis with crescents
IgA nephropathy histology features on IF
• IF: Mesangial IgA deposition (KEY/bolded)
IgA nephropathy histology features on EM
• EM: Mesangial electron dense deposits (“paramesangial”)
IgA nephropathy prognosis
• Prognosis based on serum creatinine, BP, and degree of proteinuria
– 40% of patients will slowly develop chronic kidney disease
IgA nephropathy treatment
- Fish oil may slow progression of disease
- ACE-inhibitors used to control blood pressure
- Corticosteroids, other immunosuppressants also may be used in progressive disease
Henoch-Schönlein Purpura cause
• Systemic disorder characterized by IgA deposition in multiple organs
Henoch-Schönlein Purpura manifestations
– skin–characteristic non-blanching purpura on legs and buttocks
– joints–transient arthralgias
– GI tract–abdominal pain, vomiting, melena, hematochezia
– kidney–hematuria, proteinuria; rarely progressive renal failure
post-infectious GN classic example and characteristics
- Post-streptococcal GN– classic example
- Follows infection in nephritogenic strain of group A beta-hemolytic streptococcus
- Occurs 7-14 days after pharyngitis; 14-28 days after skin infection
post-strep GN clinical features
• Sudden onset hypertension, azotemia, oliguria, edema (periorbital) and cola- or tea-colored urine
post-strep lab findings
– low C3 complement level
– Anti-streptolysin O (ASO) can be elevated (high anti-DNase B titers)
– Urinalysis: red blood cell casts, mild proteinuria
post-strep histology features on LM
• LM: Enlarged, hypercellular glomeruli. Diffuse mesangial and endocapillary proliferation with neutrophils. May see crescents.
post-strep histology features on IF
• IF: Granular capillary wall and mesangial IgG and C3
post-strep histology features on EM
• EM: Mesangial and large subepithelial “hump-like” deposits (KEY/bolded)
post-strep GN prognosis
• 95% of children will recover with conservative management
~1% progress to renal failure
• 60% of adults will recover promptly
rapidly progressive GN features
- Classic nephritic syndrome with rapid progression (days to weeks) to renal failure
- Sometimes referred to as “crescentic GN”
causes of rapidly progressive GN
– Anti-GBM/Goodpasture’s – Immune complex GN • Lupus nephritis • Post-infectious • Cryoglobulinemia – ANCA associated GN (Pauci immune)
rapidly progressive GN histology findings
- segmental necrosis (early)
- segmental necrosis and cellular crescent
Anti-GBM/Goodpasture’s Syndrome clinical findings
• Males > Females • May present as a pulmonary-renal syndrome: – Hemoptysis – Pulmonary infiltrates – Glomerulonephritis • GN alone in anti-GBM disease
Anti-GBM/Goodpasture’s Syndrome cause
• Due to circulating anti-GBM antibody
– Antigen is α3-chain of type IV collagen
Anti-GBM/Goodpasture’s Syndrome diagnosis
– + anti-GBM antibody in blood
– Linear IgG and C3 on kidney biopsy IF
Anti-GBM/Goodpasture’s Syndrome treatment
– Plasmapheresis
– Prednisone
– Cytoxan
Pauci-immune GN characteristics
• Crescenteric GN with little deposition of immune reactants
– “Pauci-immune”
– As opposed to:
• Anti-GBM disease
• IgA nephropathy
• Lupus nephritis
Pauci-immune GN causes
• Idiopathic or associated with antineutrophil cytoplasmic antibody (ANCA) vasculitis
Small vessel vasculitis diseases (3)
• Microscopic polyangiitits (MPO-ANCA/p-ANCA)
– No granulomatous inflammation and no asthma
• Wegener’s granulomatosis (PR3-ANCA/c-ANCA)
– Necrotizing granulomatous inflammation; no asthma
• Churg-Strauss syndrome
– Necrotizing granulomatous inflammation, asthma, eosinophilia