The Kidney in Systemic Disease 1/2 Flashcards
What are 4 vascular injury syndromes?
ANCA-assc glomerulonephritis
Thrombotic Microangiopathy
Lupus Nephritis
Scleroderma
What are the 2 pathogenesises of vascular disorder?
- inflammation of blood vessels
2. Loss of thromboresistance (= loss of normal resistance to clot formation)
What are the differences between medium vessel disease and small vessel disease?
medium vessel disease:
- renal infarcts and distal glomerular ischemia
- decline in GFR not assc with glomerular inflammation
- NO RBC casts
- usually ANCA negative
- aka polyarteritis nodosa
small vessel disease:
- focal necrotizing lesions with crescent formation
- active urinary sediment
- rapid progression of kidney failure (decline in GFR)
- aka microscopic polyangiitis
What is pauci-immune glomerulonephritits? When is it usually seen?
negative immunefluoresence studies usually in the setting of crescentic glomerulonephritis
*often assc with ANCAs + extra renal findings (arthritis, athralgias, myalgias, fatigue) but not always and CRESCENTIC glomerulonephritis
What are ANCAs?
anti-neutrophil cytoplasmic Abs with 2 distinct patterns:
- C-ANCA: anti-proteinase 3
- P-ANCA: anti-lysosomal myeloperoxidase
What disease(s) are assc with positive C-ANCA Abs?
granulomatosis with polyangitis (Wegner’s)
What disease(s) are assc with positive P-ANCA Abs?
- anti-GBM disease (~30% of pts)
- low titers seen in SLE
- sclerosing cholangitis, ulcerative colitis, and chron’s disease
Describe the difference between C and P ANCAs with immunofluorescence?
C-ANCA: cytosplamic staining
P-ANCA: peri-nuclear staining
How are ANCAs pathogenic?
binding of ANCAs to neutrophils activates them –>
-inc contact and adhesions with endothelial cells/vascular structures by: B-2 integrin, Mac-1, Fc-gamma
- -> endothelial cell injury (to glomeruli and blood vessels)
- inhibition of PR-3 inactivity
- EC activation
- ADCC
- complement activation via alt pathway
- monocyte activation/release of ROS and chemotactic molecules
_______ cells are the primary target in small vessel vasculitis.
endothelial cells
What is a specific and sensitive test for Wegner’s Granulomatosis?
C-ANCA
What are signs and symptoms assc with granulomatosis with polyangitis (Wegner’s)?
- Upper respiratory tract involvement with: rhinorrhea, sinusitism nasopharyngeal mucosal ulcerations
- Lower Respiratory Tract involvement with: cough, dyspnea, hemoptysis, transient pulmonary infiltrates on X-ray
- !0% have azotemia at presentation
- fever, weight loss, arthralgias/arthritis, mononeuritis multiplex, skin lesions
T or F: In most autoimmune mediated vascular necrosis, arteries and veins are involved
F: usually only arteries
**granulomatosis with polyangiitis/Weger’s has BOTH a and v!!
Describe the shape/type of glomerulonephritis of granulomatosis with polyangiitis/Wegners.
crescentric
What is the treatment of granulomatosis with polyangiitis?
cyclophosphamide based with steroids, plasmapheresis
*80-90% mortality if left untreated
What are the 2 types of TMAs (thrombotic microangiopathies)?
TTP
HUS
How are TTP and HUS differentiated?
HUS:
- hemolytic anemia
- renal dysfunction
- thrombocytopenia
TTP:
- hemolytic anemia
- renal dysfunction
- thrombocytopenia
- fever
- neurologic dysfunction
Describe the appearence of vessels on biopsy that are assc with TMAs?
onion skin
What is the pathogenesis of TMAs?
- endothelial cell loses thromboresistance
- platelet activation
- fibrin clot formation in lumen of affected vessels
- endothelial cell injury
What are 3 causes of endothelial damage in HUS?
- verotoxin producing E. coli that cause production of cytotoxic antiendothelial Abs
- chemotherapeutic agents (cyclosporine, gemcitabine, bleomycin/cisplastinum)
- radiation (BM transplant)
Familial TTP is seen with a genetic deficiency of …
ADAMTS13 (vWF cleaving protease)
T or F: inc levels of vWF multimers may directly enhance platelet aggregation.
T
What are the differences between TMA and DIC?
PT and PTT are normal in TMA and prolonged in DIC
TMAs are assc with a thrombotic diathesis
DIC are assc with a bleeding diathesis
T or F: SLE is a systemic disease that spares no organ system
T
What is the ten year survival rate of SLE?
70%
What are the 11 criteria for SLE?
mala rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, immunologic disorder, antinuclear Abs
What are the stages of lupus nephritis?
I: minimak mesangial II: mesangial proliferative III: focal proliferative IV: diffuse proliferative V: Membranous VI: Advanced sclerosing
What is the most common stage of lupus nephritis?
IV: diffuse proliferative
Class __ is mild, class ___ is moderate, and class ___ is severe.
II, III, IV
What pathologies can be seen in a biopsy of a class IV (diffuse proliferative) lupus nephritis?
wireloop lesions
hyaline thrombus (immune complex)
crescent formation
excess cells
What can be seen in EM with a pt with lupus nephritis?
subendothelial and mesengial depositis
Describe immunofluroesence pattern that is consistant with a diagnosis of lupus nephritis.
“full house immunofluoresence” = all 3 Ig present (IgG, IgM, and IgA) as well as C3 and C4
What is the treatment for SLE?
Glucocorticoids, aspirin, and hydroxychloroquine (TLR inhibitor) are FDA approved for the treatment of lupus
*immunosuppresants can also be used (class 4 = cyclophosphamide and class 5 = mycophenolate mofetil)
What class of lupus nephritis is assc with poor renal survival?
IV
What is scleroderma?
disease that involves connective tissue and the microvasculature with fibrosis and vascualr occlusion
What are the 2 subsets of scleroderma? What are they based on?
limited and diffuse cutaneous based on pattern of skin involvement
What is the epidemiology of scleroderma?
femal predominance
more frequent in AA
1 in 4000 US adults affected
How is renal involvement of scleroderma characterized? Renal crisis?
proteinuria
HYP
(mild renal dysfuction)
Renal crisis: new onset of accelerated arterial HYP and/or rapidly progressive oliguric renal failure
How is scleroderma renal crisis treated?
ACE inhibitors
What are the risk factors for scleroderma renal crisis?
- early diffuse systemic sclerosis (subtype)
- rapidly progressive skin disease
- anti-RNA pol Abs
- corticosteriod therapy
What happens to the arcuate arteries with scleroderma?
intimal and medial proliferation with luminal narrowing
*fibrinoid necrosis and thrombus is common
Describe the histology of interlobar arteries with scleroderma.
concentric sclerosing intimal thickening –> resembles onion skin
What disease from this lecture is sinopulmonay?
Wegner’s
What disease from this lecture is assc with puci-immune glomerulonephritis?
Wegner’s
What is scleroderma renal crisis?
new onset of accelerated arterial HYP and/or rapidly progressive oliguric renal failure
What is the difference between microscopic polyangiitis and polyarteritis nodosa?
microscopic polyangiitis: small vessel disease (focal necrotizing lesions with crecentric formation) that causes glomerulonephritis (usually pauci-immune crescentric)
polyarteritis nodosa: medium vessel disease that causes macroscopic areas of ischemia and infarction –> kidney damage/dec GFR
What is the pathogenesis of HUS?
Shiga toxin in circulation causes widespread endothelial injury:
- shiga toxin binds receptor on endothelial cell
- inc endothelin production
- dec NO production
- TNF released
- toxin internalized (10% of time) –> apoptosis
- pro-coag state–> thrombus formation
What is the classical presentation of HUS?
sudden onset of irritability, lethargy, weakness, pallor, and oliguira in a SMALL CHILD, 5 - 10 days following gastroenteritis
TTP treatment
plasmaphoresis
What is the characteristic feature of lupus nephritis? (occurs in 100% of pts)
proteinuria
- nephrotic syndrome in 65%
- microscopic hematuria in 80%
Glossary of terms to know:
inflammation of blood vessels, usually autoimmune
vasculitis
autoimmune ANCA-negative medium vessel arteritis
Polyarteritis nodosa
antibodies against proteinase 3 or myeloperoxidase associated with specific autoimmune diseases
ANCA
autoimmune small vessel vasculitis cause of pauci-immune crescentic glomerulonephritis associated with P-ANCA
Microscopic polyangiitis
autoimmune necrotizing granulomatous vasculitis of respiratory tract and cause of crescentic glomerulonephritis associated with C-ANCA
- Granulomatosis with polyangiitis (Wegener’s
thrombotic microangiopathy of glomeruli in small children due to Shiga toxin from diarrheal E. coli H7:O157 infection
HUS
thrombotic microangiopathy due to von Willebrand factor multimers from ADAMTS13 deficiency
TTP
immune complex-mediated glomerulonephritis of systemic lupus erythematosus (the prototype multi-system autoimmune disease)
Lupus nephritis
rapidly progressive renal failure of systemic sclerosis
scleroderma renal crisis
