Kidneys in Systemic Disease Flashcards
what is dysproteinaemia?
overproduction of immunoglobulin (a protein) by clonal expansion of cells of B cell lineage
what happens in multiple myeloma?
clonal expansion of B cells resulting in abnormal B cells producing abnormal antibodies
what is a myeloma?
cancer of plasma cells
collections of abnormal plasma cells accumulate in the bone marrow causing impairment of production of normal blood cells and monoclonal production of a paraprotein (abnormal antibody) which can potentially cause renal dysfunction
symptoms of myeloma?
bone pain weakness fatigue weight loss recurrent infections constipation, nausea, poor appetite
signs of myeloma?
anaemia (pallor, fatigue)
hypercalcaemia (constipation, nausea, poor appetite)
renal failure (thirst etc)
lytic bone lesions (often shows as lower back pain)
classic presentation of myeloma?
back pain and renal failure
what is always done in myeloma investigation?
skeletal survey
renal manifestations of myeloma?
glomerular (amyloidosis, monoclonal antibody deposition)
tubular (light chain cast nephropathy)
miscellaneous (dehydration, hypercalcaemia, contrast, bisphosphonates, NSAIDs)
how is myeloma diagnosed?
high index of suspicion
bloods serum electrophoresis (measuring immunoglobulins and free light chains)
urine (check for bence jones protein)
bone marrow biopsy (shows crowding of bone marrow)
skeletal survey
renal biopsy (not always needed)
what is bence jones protein?
monoclonal globulin protein or immunoglobulin light chain found in the urine
suggestive of multiple myeloma
how is myeloma managed?
stop any nephrotoxic drugs manage hypercalcaemia (saline + bisphosphonates) mainstay: - chemotherapy - stem cell transplant (bone marrow) plasma exchange (to remove light chains)
supportive treatment of myeloma?
dialysis
baseline investigation of myeloma?
protein electrophoresis + bence jones protein
what is amyloidosis?
deposition of extracellular amyloid (insoluble protein fibrils) in tissues or organs
over 30 causative proteins
what causes of amyloidosis?
abnormal folding of proteins which can then aggregate and become insoluble - forms a beta sheet (abnormally folded proteins are usually broken down by proteases, but these become overloaded and cant break them down)
these amyloid beta sheets deposit in tissues and cause damage
what are the 4 most common forms of amyloidosis?
primary/light chain (AL)
secondary/systemic/inflammatory (AA)
dialysis (build up of AB2M)
hereditary and old age (ATTR)
what causes AL amyloidosis?
production of abnormal immunoglobulin (antibody) light chains by plasma cells (occurs in plasma disorders e.g - multiple myeloma)
light chains enter the bloodstream and cause amyloid deposits
where does AL amyloidosis commonly affect?
heart bowel skin nerves kidneys
when does amyloidosis present and how good is life expectancy?
usually 55-60 at diagnosis
life expectancy = 6 months - 4 years if untreated
what causes AA amyloidosis?
associated with systemic inflammation and the subsequent production of acute phase protein (serum amyloid A protein)
serum amyloid A can misfold into AA amyloids which deposit in tissues
can occur in people with chronic inflammatory conditions or chronic infection (RA, IBD, psoriasis, TB, osteomyelitis etc)
where does AA amyloidosis commonly affect?
liver
spleen
kidneys
adrenals
how does amyloidosis present?
depends on organ/tissue affected
renal = nephrotic syndrome (proteinuria +/- impaired renal function, oedema, hypoalbuminaemia, hyperlipidaemia)
cardiac = restrictive cardiomyopathy > heart failure, arrhythmia
nerves = peripheral or autonomic neuropathy, orthostatic hypotension
hepatomegaly/splenomegaly/enlarged tongue
GI = malabsorption due to damage to villi
renal investigation in amyloidosis?
urinalysis + uPCR bloods (renal function, inflammatory markers, protein electrophoresis, SFLC) renal biopsy (congo red staining - pink or apple green under polarised light)
how is amyloidosis staged?
SAP scan
- scintigraphy with radiolabelled serum amyloid
how is amyloidosis managed?
no cure, just aim to reduce further deposition and preserve renal function
AA = treat underlying condition
AL = immunosuppression (steroids, chemo, stem cell transplant)
key diagnostic tool for amyloidosis?
biopsy of affected organ
abdominal fat pad biopsy
congo red stain - shows pink or apple green bifringence under polarized light
what size vessel vasculitis is more related to renal system?
small vessel (ANCA associated mainly)
what is ANCA associated vasculitis and how does it present?
necrotising polyangitis that affects capillaries, venules and arterioles
usually presents in 5th, 6th and 7th decade with constitutional symptoms
- fever
- arthralgia
- weight loss
- anorexia and malaise
may have pro-dromal symptoms for weeks to months before specific organ involvement
how is ANCA vasculitis diagnosed?
high index suspicion urinalysis (blood and protein) bloods (raised inflammatory markers, KI, anaemia) immunology (ANCA, anti MPO, anti PR3) renal biopsy
what do anti MPO and anti PR3 cause?
MPO = microscopic polyangitis = pANCA PR3 = GPA = cANCA
describe features of GPA?
anti PR3 antibodies
necrotising granulomatous inflammation of small vessels
- often in resp system (nasal collapse) and renal system
describe features of microscopic polyangitis?
MPO antibodies
small vessel vasculitis with no granulomas
systemic features
- renal, lung, skin, GI, nerves
describe features of EGPA?
associated with asthma and eosinophilia
2/3rds have skin involvement
how is vasculitis managed?
immunosuppression
- steroids, cyclophosphamide/rituximab
plasma exchange (doesn’t work much)
supportive (dialysis, ventilation)
what is SLE?
chronic autoimmune inflammatory disease of unknown origin affecting skin, joints, kidneys, lungs, NS and serous membranes
diagnostic criteria for SLE?
4 of the following - malar rash - discoid rash - photosensitivity - oral ulcers - non-erosive arthritis - pleuropericarditis - renal disease - neurologic disorder - haematological disorder positive LE cell proliferation, antibodies positive fluorescent ANA test
how is SLE diagnosed?
blood tests - raised inflammatory markers - immunology (ANA, anti dsDNA) - low complement levels urinalysis
what is lupus nephritis?
renal involvement in lupus patients
occurs in 50-60% of SLE patients
classification of lupus nephritis?
I = minimal mesangial involvement II = mesangial proliferative III = focal proliferative IV = diffuse proliferative V = membranous VI = advanced scelrosing
how is SLE managed?
depends on severity generally steroids always given immunosuppression often given - cyclophosphamide - MMF - azathioprine all patients should be on hydroxychloroquine (DMARD)
give 2 examples of localised amyloidosis?
hereditary and old age - alzheimers
ATTR - familial amyloid cardiomyopathy (mutant TTR deposits in the heart)
