Rapidly Progressive Glomerulonephritis (RPGN) Flashcards
rapidly progressive glomerulonephritis (RPGN) - defined
*clinical syndrome: acute glomerulonephritis associated with a rapid onset of severe acute kidney injury
*pathologic feature: crescents on light microscopy
*usually caused by processes that cause nephritic syndrome (the “extreme” of nephritic syndrome)
rapidly progressive glomerulonephritis (RPGN) - clinical features
*oliguria
*rapid renal failure
*variable proteinuria
*hematuria
*hypertension, often severe
essentially, severe nephritic syndrome with rapid loss of GFR
oliguria - defined
low urine output < 400 ml/day
rapidly progressive glomerulonephritis (RPGN) - urine findings
*RBCs and RBC casts
*dysmorphic RBCs
rapidly progressive glomerulonephritis (RPGN) - the CRESCENT
*crescents consist of fibrin & plasma proteins with glomerular parietal cells, monocytes, macrophages
*crescents are induced in the glomerular capillary wall, resulting in:
-movement of plasma products, including fibrinogen, into Bowman’s space with subsequent fibrin formation
-influx of macrophages and T cells
-release of proinflammatory cytokines (IL-1, TNF-alpha)
*crescent organization: cellular → fibrocellular → fibrous
3 main glomerular insults that cause RPGN
- anti-GBM disease (antibodies directly targeting the GBM)
- immune complex diseases (nephritic type immune complex disease, typically with subendothelial immune complexes that can cause severe injury)
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Pauci immune glomerulonephritis (anti-neutrophil cytoplasmic antibodies [ANCA] activate circulating immune cells which result in cell-mediated damage)
-includes GPA, EGPA, and microscopic polyangiitis (MPA)
anti-glomerular basement membrane disease (anti-GBM) - light microscopy findings
*breaks of the GBM due to fibrinoid necrosis
*CRESCENTS
anti-glomerular basement membrane disease (anti-GBM) - immunofluorescence findings
*strong linear GBM staining for IgG
*this is DIAGNOSTIC
anti-glomerular basement membrane disease (anti-GBM) - electron microscopy findings
no deposits
anti-glomerular basement membrane disease (anti-GBM) - etiology
*development of (usually IgG) autoantibodies against the non-collagenous C-terminal domain of alpha 3 subunit of type IV collagen
*development of disease is sometimes preceded by a flu-like illness (virus) or hydrocarbon or solvent exposure
*also associated with cigarette smoking
*exposure of an antigen/domain of type IV collagen that is not normally seen by the immune system
*anti-GBM disease can occur in Alport Syndrome patients who have received kidney transplant
anti-glomerular basement membrane disease (anti-GBM) - epidemiology
*renal and pulmonary: men aged 20-40
*renal limited: women aged > 60
anti-glomerular basement membrane disease (anti-GBM) - clinical presentation
*isolated renal disease or with cross-reaction with alveolar basement membranes, causing pulmonary hemorrhage (Goodpasture’s Syndrome)
*flu-like illness may precede the onset
*acutely ill with oliguria, fluid overload, nephritic syndrome, and pulmonary hemorrhage if Goodpasture’s
*positive anti-GBM antibodies; can also have positive ANCA
anti-glomerular basement membrane disease (anti-GBM) - treatment
*plasma exchange to remove the antibody
*immunosuppression to decrease antibody production (corticosteroids, cyclophosphamide)
anti-glomerular basement membrane disease (anti-GBM) - prognosis
*kidney and patient survival correlate with the degree of kidney injury at presentation
*patients who survive the first year with intact kidney function do well, relapses are uncommon
immune complex-mediated RPGN
*any nephritic immune complex-mediated glomerulonephritis can cause crescents/RPGN
*most likely to see crescentic RPGN from nephritic processes with subendothelial deposits:
-proliferative lupus nephritis
-post-infectious glomerulonephritis
-IgA nephropathy
-MPGN
lupus nephritis (class III and IV) - etiology
*immune complex deposition causing proliferative glomerulonephritis
*genetic predisposition
*inadequate clearance of nuclei from cells undergoing apoptosis
*excess nuclear antigens + B and T cell abnormalities result in auto-antibody formation (ANA and anti-dsDNA)
*activation of toll-like receptors and dendritic cells and high interferon alpha levels
*location of antibody-antigen complexes deposit determines the injury response
lupus nephritis - epidemiology
*of patients with SLE, 75% have an abnormal urinalysis
*1/3 have lupus nephritis
lupus nephritis - clinical presentation
*variable: asymptomatic proteinuria/hematuria to edema to RPGN
*lupus nephritis can change classes over time
lupus nephritis - treatments
*class I/II: monitor, ACEi/ARB
*class III/IV: steroids, immunosuppression
*maintenance therapy: MMF, azathioprine
*class V: immunosuppression
mixed cryoglobulinemic vasculitis - light microscopy findings
*MPGN-like appearance
*lobular accentuation of glomeruli
*leukocyte infiltration
*tram track double contours
*capillary lumina with hyaline thrombi “cryo plugs”
mixed cryoglobulinemic vasculitis - immunofluorescence findings
*IgM, IgG, C3, and C1q deposits (IgM prominent)
mixed cryoglobulinemic vasculitis - electron microscopy findings
*subendothelial deposits with an organized structure (crystalline)
mixed cryoglobulinemic vasculitis - etiology
*cryoglobulins are immunoglobulins that precipitate at temperatures lower than 37 C (lower than body temp)
*mixed cryos consist of polyclonal IgG and IgM that targets the IgG
*can cause immune complex formation and MPGN
*often result from chronic viral infections such as HEPATITIS C or from SLE
mixed cryoglobulinemic vasculitis - clinical presentation
*can cause multisystem disease (arthralgias, neuropathy, erythematous macules to papules)
*renal presentation can range from isolated hematuria and/or proteinuria to nephrotic or nephritis syndrome to RPGN
