Kidneys in Systemic Disease Flashcards
What is dysproteinaemia?
Overproduction of immunoglobulin by clonal expansion of cells from B cell lineage
How does dysproteinaemia affect the kidneys?
Abnormal circulating Ig reach the glomerulus and cause a variety of lesions in the kidney
What causes myeloma cast nephropathy?
Abnormal circulating Ig passes through basement membrane and forms cysts within distal tubular lamina
What causes light chain Fanconi syndrome?
Abnormal Ig forms crystals within the cytoplasm of proximal tubules
What is myeloma?
Cancer of plasma cells = collections of abnormal plasma cells accumulate in the bone marrow and impairs production of normal blood cells
What are plasma cells?
Type of white blood cells responsible for producing antibodies
Why can myeloma cause renal dysfunction?
Monoclonal proliferation of paraprotein (abnormal antibody)
What is the classic presentation of myeloma?
Back pain and renal failure
What are some symptoms of myeloma?
Bone pain, weakness, fatigue, weight loss, recurrent infections
What are some signs of myeloma?
Anaemia, hypercalcaemia, renal failure, lytic bone lesions
What are the renal manifestations of myeloma?
20-40% present with renal impairment
Glomerular = AL amyloidosis, monoclonal Ig deposition
Tubular = light chain cast nephropathy
What are some miscellaneous renal manifestations of myeloma?
Dehydration, hypercalcaemia, contrast, bisphosphonates, NSAIDs
What are the best two investigations for diagnosing myeloma?
Protein electrophoresis and Bence Jones protein urine analysis
What investigations can be done to diagnose myeloma?
Bloods = serum protein electrophoresis and serum free light chains
Urine = Bence Jones protein
Bone marrow biopsy, skeletal survey, renal biopsy
What is the management for myeloma?
Stop nephrotoxics and supportive dialysis
Manage hypercalcaemia = saline +/- bisphosphonates
Chemotherapy and stem cell transplant
Plasma exchange to remove light chains
What is amyloidosis?
Deposition of extracellular amyloid (insoluble protein fibrils)
Why does amyloidosis occur?
Due to abnormal folding of proteins which then aggregate and become insoluble = causes breakdown of usual degradation pathway for abnormal proteins
How many forms of amyloidosis are there?
Over 30 identified proteins = inherited and acquired forms
What are the 4 most common forms of amyloidosis?
Primary/light chain (AL)
Secondary/systemic/inflammatory (AA)
Dialysis (Abeta2M)
Hereditary and old age (ATTR)
What is amyloidosis an important differential for?
Nephrotic range proteinuria
What is AL amyloidosis?
Deposition of abnormal Ig light chains from plasma cells = light chains enter bloodstream and cause amyloid deposits
What are some features of AL amyloidosis?
Affects heart, bowel, skin, nerves and kidneys
Typical age is 55-60
Life expectancy of 6 months - 4 years (untreated)
What is AA amyloidosis associated with?
Systemic inflammation = production of acute phase protein (serum amyloid A protein)
How common is AA amyloidosis in patients with chronic inflammatory conditions or infections?
Develops in 5% = rheumatoid arthritis, psoriasis, IBD, TB, osteomyelitis, bronchiectasis
Where in the body does AA amyloidosis affect?
Liver, spleen, kidneys and adrenals
What are the renal manifestations of amyloidosis?
Nephrotic range proteinuria +/- impaired renal function
What are the extra-renal manifestations of amyloidosis?
Cardiomyopathy, peripheral or autonomic neuropathy, hepatomegaly, splenomegaly, malabsorption
What are some basic investigations that can be done for amyloidosis?
Urinalysis and uPCR
Blood tests = renal function, inflammatory markers, protein electrophoresis, SFLC
What biopsies can be done for amyloidosis?
Renal = congo red staining gives apple green birefringence under polarised light (diagnostic)
Can also do abdominal fat pad or rectal biopsy
How are SAP scans used to investigate amyloidosis?
Scintigraphy with radiolabelled serum amyloid = shows extent of disease
What is the aim of amyloidosis treatment?
Not curative = aim to reduce further deposition and preserve organ function
What are some of the treatments for amyloidosis?
AA = treat underlying cause AL = immunosuppression (steroids, chemotherapy, stem cell transplant)
What type of vasculitis normally affects the kidneys?
Small vessel = usually ANCA positive
How does vasculitis affect the kidneys?
Causes necrotising polyangiitis that affects capillaries, venules and arterioles
How does vasculitis present?
Usually age 50-70
Vague symptoms = fever, migratory pain, arthralgia, weight loss, anorexia, malaise, may last for weeks to months before specific organ involvement
How is vasculitis diagnosed?
Urinalysis = active urine, positive for blood/protein
Bloods = raised inflammatory markers, AKI, anaemia
Immunology = ANCA, anti-MPO, anti-PR3
Renal biopsy
What types of ANCA are implicated in vasculitis?
pANCA = peri-nuclear (MPO) cANCA = cytoplasmic (PR3)
What is the immunology of some small vessel vasculitis that affect the kidneys?
GPA = 95% ANCA positive (cANCA), 65% have anti-PR3 MPA = 90% ANCA positive (pANCA), 55% anti-MPO positive
How is small vessel vasculitis treated?
Immunosuppression = steroids, cyclophosphamide, rituximab
Plasma exchange
Supportive = dialysis, ventilation
What is systemic lupus erythematous (SLE)?
Chronic auto-immune inflammatory disease of unknow origin = 10 times more common in women, age of onset usually 20-30
What areas of the body are affected by SLE?
Skin, joints, kidneys, lungs, nervous system and serous membranes
What races is SLE more severe in?
African Americans and Hispanics
What are some of the features of SLE?
Malar/discoid rash, oral ulcers, photosensitivity, haemolytic anaemia, thrombocytopenia, fever, weight loss
What investigations can be done for SLE?
Blood tests = raised inflammatory markers, ANA positive, anti-dsDNA positive, low complement levels
Must do urinalysis and renal biopsy
What are the differentials for SLE?
Sjogren’s syndrome, fibromyalgia, primary anti-phospholipid syndrome, thrombotic micro-angiopathies
How common is lupus nephritis in patients with SLE?
Up to 50% will have renal involvement at presentation and up to 60% during the course of their disease
What is the most common abnormality seen in lupus nephritis?
Proteinuria
What are class I and II lupus nephritis?
I = minimal mesangial II = mesangial proliferation
What are class III and IV lupus nephritis?
III = focal proliferation IV = diffuse proliferation
What are class V and VI lupus nephritis?
V = membranous VI = advanced sclerosing
How are class I and II lupus nephritis treated?
I = treat extra-renal manifestations II = proteinuria >3gm treated with steroids or CNI
How are class III and IV lupus nephritis treated?
Steroids + cyclophosphamide
Switch to steroids + MMF in 3 months if first combination not working
What is the maintenance treatment for class III and IV lupus nephritis?
Azathioprine or MMF + low dose steroids for 1 year
How is a patient with class V lupus nephritis but normal kidney function and non-nephrotic range proteinuria treated?
Conservative management and treatment dictated by extra-renal manifestations
How is a patient with class V lupus nephritis and persistent proteinuria treated?
Steroids + cyclophosphamide and/or CNI or MMF or azathioprine
What medication should all patients with lupus be taking?
Hydroxychloroquine
What is the prognosis of SLE?
Most have relapsing/remitting disease course
ESRD affects 8-15% of patients with lupus nephritis
What are poor prognostic factors for SLE?
Renal disease, male sex, young or older age at presentation, poor socio-economic class, anti-phospholipid syndrome, high overall disease activity
