Renal Involvement in Systemic Conditions Flashcards
What multi system disorders can affect the kidneys?
Remember “VITAMIN D”
Vascular - hypertension, reno vascular disease
Infective - hepatitis B, hepatitis C, HIB, infective endocarditis, TB, AA amyloidosis
Autoimmune - vasculitis, SLE, antiphospholipid syndrome, scleroderma, sarcoidosis, RA, AA amyloidosis
Metabolic - DM, Gaucher’s disease
Neoplastic - multiple myeloma, amyloid light chain amyloidosis, lymphoma/ leukaemia
Others - sickle cell anaemia, thrombotic microangiopathy
How does polyarteritis nodosa (PAN) affect the kidney?
PAN = multisystem disorder causing aneurysmal dilatation of medium sized arteries
Presents as hypertension, polyneuropathy and ischaemic infarction of a number of organs (e.g. heart, gut, skin and brain)
Aneurysms may be visible on renal arteriography
Gives rise to slowly progressive CKD with severe hypertension. Rapidly progressive renal failure is rare
What conditions are associated with PAN?
M>F Elderly Typically ANCA negative Drug use Hepatitis B infection
How is PAN affecting the kidney treated?
Immunosuppression, but less effective than for microscopic polyangitis
What is the pathology of scleroderma?
Chronic multi system disease with fibrosis and vasculopathy of the skin and visceral organs
Plasmacytoid dendritic cells produce high levels of CXCL4 associated with both lung and skin fibrosis as well as pulmonary artery hypertension
How does scleroderma affect the kidney?
10% patients have a scleroderma renal crisis = accelerated hypertension, rapidly progressive renal failure and proteinuria
“Onion skinning” seen on renal biopsy in arcuate and interlobular arteries caused by vessel intimal proliferation, fibrin thrombi and fibrinoid necrosis
How is scleroderma renal crisis treated?
ACEi
What is haemolytic uraemic syndrome (HUS)?
Characterised by intravascular haemolysis with red cell fragmentation (microangiopathic haemolytic anaemia), thrombocytopenia and AKI due to thrombosis in small arteries/ arterioles
Similar features seen in DIC, but coagulation tests are normal in HUS
3 types:
1) Diarrhoea associated (typical HUS)
2) Atypical HUS
3) Metabolism associated HUS
What organisms cause diarrhoea associated HUS?
Usually follows febrile illness, particularly gastroenteritis associated with E.coli O157:H7
What is the pathology of E.coli induced HUS?
E.coli O157:H7 produces a verocytotoxin (or shiga toxin) with a pathogenic A unit that inhibits protein synthesis and initiates endothelial damage
B units facilitate entry of A units into endothelial cells by binding to receptor Gb3 on the endothelial cell. Toxins are transported to and into endothelial cells via neutrophils
How is typical HUS managed?
Most patients with D+ HUS recover renal function but commonly require supportive care - e.g. fluid and electrolyte balance, anti-hypertensives, nutritional support and dialysis
Plasmapharesis for this the of HUS is NOT useful
Antibiotics and anti motility agents for diarrhoea increase risk of HUS and complications
What is the prognosis of typical HUS?
5% die during acute episode
5% develop ESKD
30% have evidence of long term damage with persistent proteinuria
What is atypical HUS?
Complement driven illness often related to deficiency of complement factor H (CFH) or complement factor I (CFI).
Factor H is a soluble protein produced by the liver, which regulates the activity of the alternative complement activation pathway - it protects host cell surfaces from complement mediated damage
In some families with aHUS a mutation has been linked to another complement regulatory protein, CD46. This is highly expressed in the kidney and prevents glomerular C3 activation. Loss of function mutation in CD46 causes unopposed complement activation and development of HUS
Functional deficiency of these factors can occur due to antibody formation, either isolated or as part of another autoimmune disease such as SLE
How is aHUS managed?
Treatment difficult, severe hypertension and recurrence can occur:
1) Plasmapharesis or plasma infusion is used at initiation of therapy in the majority of patients until diagnosis is clear
2) C5 activation is a key step in the activation of the complement cascade. Eculizumab is a monoclonal humanised C5 antibody
3) Liver transplant can be curative in patients with CFH or CFI mutations
What causes sporadic aHUS?
Pregnancy SLE Scleroderma Malignant hypertension Metastatic cancer HIV infection Drugs (COC, cyclosporin, tacrolimus, cisplatin, bleomycin, mitomycin and heparin)
