Kidneys in Systemic Disease

Question 1

what is dysproteinaemia?

Answer 1

overproduction of immunoglobulin (a protein) by clonal expansion of cells of B cell lineage

Question 2

what happens in multiple myeloma?

Answer 2

clonal expansion of B cells resulting in abnormal B cells producing abnormal antibodies

Question 3

what is a myeloma?

Answer 3

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

Question 4

symptoms of myeloma?

Answer 4

bone pain
weakness
fatigue
weight loss
recurrent infections
constipation, nausea, poor appetite

Question 5

signs of myeloma?

Answer 5

anaemia (pallor, fatigue)
hypercalcaemia (constipation, nausea, poor appetite)
renal failure (thirst etc)
lytic bone lesions (often shows as lower back pain)

Question 6

classic presentation of myeloma?

Answer 6

back pain and renal failure

Question 7

what is always done in myeloma investigation?

Answer 7

skeletal survey

Question 8

renal manifestations of myeloma?

Answer 8

glomerular (amyloidosis, monoclonal antibody deposition)
tubular (light chain cast nephropathy)
miscellaneous (dehydration, hypercalcaemia, contrast, bisphosphonates, NSAIDs)

Question 9

how is myeloma diagnosed?

Answer 9

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)

Question 10

what is bence jones protein?

Answer 10

monoclonal globulin protein or immunoglobulin light chain found in the urine
suggestive of multiple myeloma

Question 11

how is myeloma managed?

Answer 11

stop any nephrotoxic drugs
manage hypercalcaemia (saline + bisphosphonates)
mainstay:
- chemotherapy
- stem cell transplant (bone marrow)
plasma exchange (to remove light chains)

Question 12

supportive treatment of myeloma?

Answer 12

dialysis

Question 13

baseline investigation of myeloma?

Answer 13

protein electrophoresis + bence jones protein

Question 14

what is amyloidosis?

Answer 14

deposition of extracellular amyloid (insoluble protein fibrils) in tissues or organs
over 30 causative proteins

Question 15

what causes of amyloidosis?

Answer 15

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

Question 16

what are the 4 most common forms of amyloidosis?

Answer 16

primary/light chain (AL)
secondary/systemic/inflammatory (AA)
dialysis (build up of AB2M)
hereditary and old age (ATTR)

Question 17

what causes AL amyloidosis?

Answer 17

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

Question 18

where does AL amyloidosis commonly affect?

Answer 18

heart
bowel
skin
nerves
kidneys

Question 19

when does amyloidosis present and how good is life expectancy?

Answer 19

usually 55-60 at diagnosis

life expectancy = 6 months - 4 years if untreated

Question 20

what causes AA amyloidosis?

Answer 20

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)

Question 21

where does AA amyloidosis commonly affect?

Answer 21

liver
spleen
kidneys
adrenals

Question 22

how does amyloidosis present?

Answer 22

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

Question 23

renal investigation in amyloidosis?

Answer 23

urinalysis + uPCR
bloods (renal function, inflammatory markers, protein electrophoresis, SFLC)
renal biopsy (congo red staining - pink or apple green under polarised light)

Question 24

how is amyloidosis staged?

Answer 24

SAP scan

- scintigraphy with radiolabelled serum amyloid

Question 25

how is amyloidosis managed?

Answer 25

no cure, just aim to reduce further deposition and preserve renal function
AA = treat underlying condition
AL = immunosuppression (steroids, chemo, stem cell transplant)

Question 26

key diagnostic tool for amyloidosis?

Answer 26

biopsy of affected organ
abdominal fat pad biopsy
congo red stain - shows pink or apple green bifringence under polarized light

Question 27

what size vessel vasculitis is more related to renal system?

Answer 27

small vessel (ANCA associated mainly)

Question 28

what is ANCA associated vasculitis and how does it present?

Answer 28

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

Question 29

how is ANCA vasculitis diagnosed?

Answer 29

high index suspicion
urinalysis (blood and protein)
bloods (raised inflammatory markers, KI, anaemia)
immunology (ANCA, anti MPO, anti PR3)
renal biopsy

Question 30

what do anti MPO and anti PR3 cause?

Answer 30

MPO = microscopic polyangitis = pANCA
PR3 = GPA = cANCA

Question 31

describe features of GPA?

Answer 31

anti PR3 antibodies
necrotising granulomatous inflammation of small vessels
- often in resp system (nasal collapse) and renal system

Question 32

describe features of microscopic polyangitis?

Answer 32

MPO antibodies
small vessel vasculitis with no granulomas
systemic features
- renal, lung, skin, GI, nerves

Question 33

describe features of EGPA?

Answer 33

associated with asthma and eosinophilia

2/3rds have skin involvement

Question 34

how is vasculitis managed?

Answer 34

immunosuppression
- steroids, cyclophosphamide/rituximab
plasma exchange (doesn’t work much)
supportive (dialysis, ventilation)

Question 35

what is SLE?

Answer 35

chronic autoimmune inflammatory disease of unknown origin affecting skin, joints, kidneys, lungs, NS and serous membranes

Question 36

diagnostic criteria for SLE?

Answer 36

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

Question 37

how is SLE diagnosed?

Answer 37

blood tests
- raised inflammatory markers
- immunology (ANA, anti dsDNA)
- low complement levels
urinalysis

Question 38

what is lupus nephritis?

Answer 38

renal involvement in lupus patients

occurs in 50-60% of SLE patients

Question 39

classification of lupus nephritis?

Answer 39

I = minimal mesangial involvement
II = mesangial proliferative
III = focal proliferative
IV = diffuse proliferative
V = membranous
VI = advanced scelrosing

Question 40

how is SLE managed?

Answer 40

depends on severity
generally steroids always given
immunosuppression often given 
- cyclophosphamide
- MMF
- azathioprine
all patients should be on hydroxychloroquine (DMARD)

Question 41

give 2 examples of localised amyloidosis?

Answer 41

hereditary and old age - alzheimers

ATTR - familial amyloid cardiomyopathy (mutant TTR deposits in the heart)