Renal Involvement in Systemic Disease

28/04/2013 by admin | Renal

Diabetes Mellitus:

  1. DM causes renal disease (30% have nephropathy after 20 years).
  2. It accounts for 10% of renal replacement therapy
  3. Initial diabetic renal disease manifests as microalbuminuriaproteinurianephrotic syndrome
  4. Loss of excretory function = increasing creatinine and urea
  5. If nephropathy – suspect retinopathy and neuropathy
  6. Mx: aggressive ACEi therapy and good glycaemic control paramount

 

Multiple myeloma:

  1. Acute or chronic renal impairment
  2. Complete protein electrophoresis for paraproteinaemia, urine electrophoresis for Bence-Jones proteins and undertake immunoglobulin estimations
  3. Due to direct toxicity of Ig light chains on tubular cells, hypercalcaemia, dehydration, hyperuricaemia, renal amyloid, hyperviscosity, infection.
  4. Tx: mx MM, rapid correction of hypovolaemia and hypercalcaemia

 

Amyloidosis:

  1. Characterised by deposition of protein fibrils in organs (including kidneys)
  2. Primary amyloidosis (amyloid AL) due to myeloma or lymphoma
  3. Secondary amyloidosis (amyloid AA) due to infections or inflammation
  4. P/c: proteinuria (nephrotic syndrome)
  5. Biopsy = eosinophillic tissue infiltration stains +ve with Congo red and exhibits green birefringence under polarized light. Prognosis = poor.

 

Haemolytic/uraemic syndrome:

  1. Haemolysis and acute renal failure, diarrhoea, linked to E.coli O:157 – producing verocytotoxin = endothelial damage.
  2. Will show haemolysis, thrombocytopaenia, renal failure.
  3. Biopsy = fibrin thrombi occluding glomerular tufts.
  4. In severe cases – plasmaphoresis may be indicated.

 

Renovascular disease:

  1. Renal artery stenosis:
  2. HTN, renal impairment, fluid overload and pulmonary oedema
  3. Renal bruit may be heard and USS may show small or asymmetrical kidneys
  4. Renal angiography = stenosis
  5. Tx: underlying CVD RFs, angioplasty or stenting used for resistant HTN or deteriorating renal function
  6. Obstruction can also be due to embolism of renal arteries or renal artery dissection (p/c = loin pain, and renal impairment)
  7. Fibromuscular dysplasia:
  8.  ‘Beaded’ renal artery on angiography, seen in young females and is a serious cause of HTN

 

Renal vasculitis:

Wegener’s granulomatosis:

  1. Rare: 600 new cases/year
  2. Granulomatous disease of upper airways (nose/sinus/trachea)
  3. Lung and renal impairment due to focal necrotizing GN
  4. It must be a differential in pts with upper airways disease/ling masses/rapidly progressive GN
  5. cANCA is +ve (pattern of staining of cytoplasmic components of neutrophils after applying serum IgG antibodies is studied.
  1. 2 patterns of staining are found = predominantly cANCA (antigen = proteinase) or predominantly (perinuclear) pANCA (antigen = myeloperoxidase).
    1. 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.
    2. o cANCA = Wegener’s in 90% of cases (titre reflects disease severity)
  2. Renal biopsy will show focal necrotizing GN (with crescent formation and granuloma)
  3. Tx: PROMPT to avoid renal failure! Give aggressive immunosuppression, corticosteroids and cyclophosphamide.

 

Goodpastures syndrome:

  1. Rare (50/y)
  2. Pulmonary haemorrhage, haematuria, and rapidly progressive renal failure
  3. Cause: auto-antibody against collagen in basement membrane (=anti-glomerular basement membrane antibody [anti-GBM]) – will be shown in blood.
  4. Biopsy = crescentric GN with linear antibody staining along the GBM on immunoflouresence.
  5. Lung function = increased carbon monoxide transfer factor (KCO), consistent with pulmonary haemorrhage because Hb binds CO well.
  6. Tx: plasmpheresis to remove antibody and immunosuppression with corticosteroids and cyclophosphamide.

 

Polyarteritis nodosa:

  1. Affects larger blood vessels
  2. Non-specific symptoms: weight loss, fever, malaise, abdo pain
  3. Angiography = micro-aneurysms, arterial narrowing
  4. Biopsy = of affected tissue may be diagnostic
  5. ANCA –ve
  6. Associated to Hep B infection
  7. Renal involvement = haematuria, proteinuria
  8. Tx: immunosuppression

 

SLE:

  1. Renal disease in 50% of SLE pts
  2. Mild (proteinuria, haematuria) severe (nephrotic syndrome, rapidly progressive renal failure)
  3. Presence of haematuria/proteinuria/RBC casts = significant glomerular lesion (Ix: biopsy).
  4. Patterns of renal disease: focal/segmental proliferative GN, membranous GN, or diffuse proliferative GN with crescents.
  5. Immunology varies:
  6. +ve anti-nuclear antibody ANA – (90%)
  7. Antibodies to double stranded DNA (anti-dsDNA antibodies) = highly specific for SLE. In renal disease anti-dsDNA Abs titre may be suppressed.
  8. Anti-bodies to extractable nuclear antigens (ENAs, such as Smith Sm, or Ro-SS-A) – (40%)
  1. Antibodies to plts, RBCs, phospholipid are also common.
  2. Complement C4 and C3 can be suppressed
  3. ESR (but not CRP) will be elevated
  4. Tx: corticosteroids, immunosuppressive agents (cyclophosphamide, azathioprine).

 

Henoch-Schonlein purpura (HSP)

  1. Common in children, rare in adults
  2. May be due to autoimmune response to an infective agent?!?
  3. 1/3 have a preceding URTI
  4. p/c: arthralgia, malaise, abdo pain, and purpuric rash on extensor surfaces (elbows, knees, buttocks).
  5. Renal involvement consists of self-limiting focal GN (and occasionally progressive renal failure)

 

Scleroderma:

  1. Renal involvement in 25%
  2. Occurs early or late in disease – and accounts for 40% of deaths
  3. 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.
  4. Immunological tests show antibodies to Scl-70 (enzyme topoisomerase I) and often RNA polymerases 1-3 (associated to severe disease).
  5. Anti-centromere antibodies associated with mild cutaneous disease.
  6. Tx HTN and uraemia with ACEi

 

Cryoglobulinaemia:

  1.  ‘Cryoglobulins’ = immunoglobulins that precipitate in the cold are produced in myeloproliferative diseases
  2. SLE = polyclonal bands, type 2 cryoglobulinaemia
  3. Chronic infection / hepatitis = monoclonal bands, type 1 cryoglobulinaemia
  4. Renal disease can occur ranging from asymptomatic proteinurianephrotic syndromeacute renal failure
  5. p/c: palpable purpuric skin rash-urticaria.
  6. Tx: plasma exchange may be helpful

 

Summary (condition – diagnostic autoantibodies– treatment):

  1. Goodpasture’s syndrome = anti-glomerular basement membrane (anti-GBM) antibody
  2. Microscopic polyarteritis AND most other vasculitides! = pANCA
  3. Churg-Strauss syndrome = eosinophils and CXR
  4. Henoch-Schonlein purpura = none
  5. Wegener’s granulomatosis = cANCA
  6. SLE – ANA/anti-dsDNA/anti-Smith – tx = corticosteroids, anti-malarials (chloroquine), cyclophosphamide
  1. Scleroderma diffuse = ANA and Scl-70
  2. Scleroderma (CREST) = anti-centromere
  3. Cryoglobulinaemia type 1/2/3 = cryoglobulin monoclonal/polyclonal IgM/polyclonal antibody
  4. Drug induced lupus = antihistone
  5. 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).
  6. Primary biliary cirrhosis = antimitochondrial
  7. Coeliac disease = antigliadin and antiendomysial
  8. Pemphigus vulgaris = anti-desmoglein
  9. Hashimoto’s thyroiditis = antimicrosomal and antithyroglobulin
  10. Polymyositis or dermatomyositis = anti-Jo-1
  11. Sjogrens syndrome = anti-SS-A (anti-Ro), anti-SS-B (anti-La)
  12. Mixed connective tissue disease = anti-U1-RNP (ribonucleoprotein)
  13. Autoimmune hepatitis = anti-smooth muscle
  14. Type 1 DM = anti-glutamate decarboxylase 
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