- DM causes renal disease (30% have nephropathy after 20 years).
- It accounts for 10% of renal replacement therapy
- Initial diabetic renal disease manifests as microalbuminuriaproteinurianephrotic syndrome
- Loss of excretory function = increasing creatinine and urea
- If nephropathy – suspect retinopathy and neuropathy
- Mx: aggressive ACEi therapy and good glycaemic control paramount
- Acute or chronic renal impairment
- Complete protein electrophoresis for paraproteinaemia, urine electrophoresis for Bence-Jones proteins and undertake immunoglobulin estimations
- Due to direct toxicity of Ig light chains on tubular cells, hypercalcaemia, dehydration, hyperuricaemia, renal amyloid, hyperviscosity, infection.
- Tx: mx MM, rapid correction of hypovolaemia and hypercalcaemia
- Characterised by deposition of protein fibrils in organs (including kidneys)
- Primary amyloidosis (amyloid AL) due to myeloma or lymphoma
- Secondary amyloidosis (amyloid AA) due to infections or inflammation
- P/c: proteinuria (nephrotic syndrome)
- Biopsy = eosinophillic tissue infiltration stains +ve with Congo red and exhibits green birefringence under polarized light. Prognosis = poor.
- Haemolysis and acute renal failure, diarrhoea, linked to E.coli O:157 – producing verocytotoxin = endothelial damage.
- Will show haemolysis, thrombocytopaenia, renal failure.
- Biopsy = fibrin thrombi occluding glomerular tufts.
- In severe cases – plasmaphoresis may be indicated.
- Renal artery stenosis:
- HTN, renal impairment, fluid overload and pulmonary oedema
- Renal bruit may be heard and USS may show small or asymmetrical kidneys
- Renal angiography = stenosis
- Tx: underlying CVD RFs, angioplasty or stenting used for resistant HTN or deteriorating renal function
- Obstruction can also be due to embolism of renal arteries or renal artery dissection (p/c = loin pain, and renal impairment)
- Fibromuscular dysplasia:
- ‘Beaded’ renal artery on angiography, seen in young females and is a serious cause of HTN
- Rare: 600 new cases/year
- Granulomatous disease of upper airways (nose/sinus/trachea)
- Lung and renal impairment due to focal necrotizing GN
- It must be a differential in pts with upper airways disease/ling masses/rapidly progressive GN
- cANCA is +ve (pattern of staining of cytoplasmic components of neutrophils after applying serum IgG antibodies is studied.
- 2 patterns of staining are found = predominantly cANCA (antigen = proteinase) or predominantly (perinuclear) pANCA (antigen = myeloperoxidase).
- o pANCA = microscopic polyangiitis: inflammation of small blood vessels. P/c: multi-system or single organ involvement. Kidneys, skin, brain, nerves affected. Rapid progressive renal impairment. Tx in same was as you would for Wegener’s.
- o cANCA = Wegener’s in 90% of cases (titre reflects disease severity)
- Renal biopsy will show focal necrotizing GN (with crescent formation and granuloma)
- Tx: PROMPT to avoid renal failure! Give aggressive immunosuppression, corticosteroids and cyclophosphamide.
- Rare (50/y)
- Pulmonary haemorrhage, haematuria, and rapidly progressive renal failure
- Cause: auto-antibody against collagen in basement membrane (=anti-glomerular basement membrane antibody [anti-GBM]) – will be shown in blood.
- Biopsy = crescentric GN with linear antibody staining along the GBM on immunoflouresence.
- Lung function = increased carbon monoxide transfer factor (KCO), consistent with pulmonary haemorrhage because Hb binds CO well.
- Tx: plasmpheresis to remove antibody and immunosuppression with corticosteroids and cyclophosphamide.
- Affects larger blood vessels
- Non-specific symptoms: weight loss, fever, malaise, abdo pain
- Angiography = micro-aneurysms, arterial narrowing
- Biopsy = of affected tissue may be diagnostic
- ANCA –ve
- Associated to Hep B infection
- Renal involvement = haematuria, proteinuria
- Tx: immunosuppression
- Renal disease in 50% of SLE pts
- Mild (proteinuria, haematuria) severe (nephrotic syndrome, rapidly progressive renal failure)
- Presence of haematuria/proteinuria/RBC casts = significant glomerular lesion (Ix: biopsy).
- Patterns of renal disease: focal/segmental proliferative GN, membranous GN, or diffuse proliferative GN with crescents.
- Immunology varies:
- +ve anti-nuclear antibody ANA – (90%)
- Antibodies to double stranded DNA (anti-dsDNA antibodies) = highly specific for SLE. In renal disease anti-dsDNA Abs titre may be suppressed.
- Anti-bodies to extractable nuclear antigens (ENAs, such as Smith Sm, or Ro-SS-A) – (40%)
- Antibodies to plts, RBCs, phospholipid are also common.
- Complement C4 and C3 can be suppressed
- ESR (but not CRP) will be elevated
- Tx: corticosteroids, immunosuppressive agents (cyclophosphamide, azathioprine).
Henoch-Schonlein purpura (HSP)
- Common in children, rare in adults
- May be due to autoimmune response to an infective agent?!?
- 1/3 have a preceding URTI
- p/c: arthralgia, malaise, abdo pain, and purpuric rash on extensor surfaces (elbows, knees, buttocks).
- Renal involvement consists of self-limiting focal GN (and occasionally progressive renal failure)
- Renal involvement in 25%
- Occurs early or late in disease – and accounts for 40% of deaths
- May present as active sediment (=haematuria with RBC casts), or ominously as a ‘scleroderma renal crisis’ – with treatment resistant HTN rapidly progressive uraemia and ‘onion skin’ renal histology.
- Immunological tests show antibodies to Scl-70 (enzyme topoisomerase I) and often RNA polymerases 1-3 (associated to severe disease).
- Anti-centromere antibodies associated with mild cutaneous disease.
- Tx HTN and uraemia with ACEi
- ‘Cryoglobulins’ = immunoglobulins that precipitate in the cold are produced in myeloproliferative diseases
- SLE = polyclonal bands, type 2 cryoglobulinaemia
- Chronic infection / hepatitis = monoclonal bands, type 1 cryoglobulinaemia
- Renal disease can occur ranging from asymptomatic proteinurianephrotic syndromeacute renal failure
- p/c: palpable purpuric skin rash-urticaria.
- Tx: plasma exchange may be helpful
Summary (condition – diagnostic autoantibodies– treatment):
- Goodpasture’s syndrome = anti-glomerular basement membrane (anti-GBM) antibody
- Microscopic polyarteritis AND most other vasculitides! = pANCA
- Churg-Strauss syndrome = eosinophils and CXR
- Henoch-Schonlein purpura = none
- Wegener’s granulomatosis = cANCA
- SLE – ANA/anti-dsDNA/anti-Smith – tx = corticosteroids, anti-malarials (chloroquine), cyclophosphamide
- Scleroderma diffuse = ANA and Scl-70
- Scleroderma (CREST) = anti-centromere
- Cryoglobulinaemia type 1/2/3 = cryoglobulin monoclonal/polyclonal IgM/polyclonal antibody
- Drug induced lupus = antihistone
- Rheumatoid arthritis = anti-IgG (=rheumatoid factor), anti-citrullinated protein antibody (ACPA) tests including = anti-CCP (cyclic citrullinated peptide) test and the anti-MCV assay (antibodies against mutated citrullinated Vimentin).
- Primary biliary cirrhosis = antimitochondrial
- Coeliac disease = antigliadin and antiendomysial
- Pemphigus vulgaris = anti-desmoglein
- Hashimoto’s thyroiditis = antimicrosomal and antithyroglobulin
- Polymyositis or dermatomyositis = anti-Jo-1
- Sjogrens syndrome = anti-SS-A (anti-Ro), anti-SS-B (anti-La)
- Mixed connective tissue disease = anti-U1-RNP (ribonucleoprotein)
- Autoimmune hepatitis = anti-smooth muscle
- Type 1 DM = anti-glutamate decarboxylase