Systemic Disease Flashcards
What is the most common systemic disease with renal involvement?
Diabetes
What is a dysproteinaemia?
Overproduction of immunoglobulin
What type of B cell is responsible for the production of antibodies?
Plasma cell
Describe how myeloma affects the production of other blood cells?
Clonal expansion of B cells (abnormal)
Make abnormal antibodies
These abnormal cells clog the bone marrow
This blocks normal production of other blood cells
What are the main myeloma symptoms?
Bone Pain Weakness Fatigue Weight Loss Recurrent infections
must be a differential for anyone with back pain + renal failure
What signs can indicate myeloma?
Anaemia
Hypercalcaemia
Renal Failure
Lytic bone lesions
What imaging can be carried out if suspicious of lytic lesions?
Skeletal Survey
Why does the renal aspect of myeloma have a multifactorial aetiology?
Hypercalcaemia makes pt more prone to stones and impaired renal function
Pt may take NSAIDs for their bone pain and damage their kidneys with the drug
What can be seen histologically in the kidney in Myeloma?
Cast Nephropathy (Myeloma Kidney) - Free light chains form waxy casts within the tubular lumen
What blood tests should you do if there is a high clinical suspicion of myeloma?
Serum Protein Electrophoresis
Serum Free light chains
What should you look for in a patients urine if you suspect myeloma?
Bence-Jones Protein
Where would you biopsy if you suspect myeloma?
Bone Marrow Biopsy
Renal Biopsy
What management is recommended in myeloma?
- Stop nephrotoxics
- Manage hypercalcaemia
REFER TO HAEMATOLOGY
- Chemotherapy
- Stem cell transplant
What supportive measure is an option in myeloma?
Supportive - Dialysis
What is the aim of Plasma exchange in conditions such as myeloma?
To remove the excess light chains
however this tx is not completely successful
What is amyloidosis?
Deposition of extracellular amyloid (insoluble protein)
in tissues or organs
Why is amyloid insoluble?
Protein is folded wrong way
Aggregates
Immune system cant break new protein down
How many different types of protein can cause amyloidosis?
30
What are the 4 most common types of amyloidosis?
Primary / Light chain (AL)
Secondary / Systemic / Inflammatory (AA)
Dialysis (Previously a problem as Aβ2M wasnt removed during dialysis)
Hereditary and old age (ATTR)
AL amyloidosis involves the deposition of light chains where in the body?
heart bowel skin nerves kidneys
When are patients usually diagnosed with AL amyloidosis, and what is the life expectancy from this point if they were untreated?
Age at diagnosis 55-60 years
Life expectancy 6 months – 4 years (untreated)
What acute phase protein is produced in AA amyloidosis?
serum amyloid A protein (SAA)
Patients with chronic inflammatory conditions or infections are more likely to develop AA Amyloidosis. TRUE/FALSE?
TRUE
Chronic infl. - RA, IBD, psoriasis
Chronic inf. - TB, osteomyelistis, bronchiectasis
Where in the body is most commonly affected by AA Amyloidosis?
liver
spleen
kidneys
adrenals
How does amyloidosis present?
Nephrotic range proteinuria +/- impaired renal function
Then dependent on where is affected:
- Cardiomyopathy (HEART)
- peripheral /autonomic neuropathy (NERVES)
- Hepatomegaly / Splenomegaly (LIVER/SPLEEN)
- malabsorption (BOWEL)
What investigations should be completed if you suspect amyloidosis
Urinalysis + PCR
Bloods
- renal function
- infl. markers
- protein electrophoresis (to rule out myeloma)
Renal Biopsy
Congo red staining (apple green under polarised light)
If patients are not suitable for a renal biopsy, where else can we take the biopsy from?
abdominal fat pad
or rectal biopsy
What is a SAP scan?
Scintigraphy with radiolabelled serum amyloid
=> shows extent of disease
(kinda looks like a PET scan)
What are the aims of amyloidosis tx if there is no cure?
- reduce further deposition
- preserve organ function
What treatments can be given for AL Amyloidosis?
Immunosuppression
Steroids
chemotherapy
stem cell transplant
Where are amyloidosis patients referred to?
UCL – National Amyloidosis Centre (London)
At what age does an ANCA positive vasculitis usually present?
5th, 6th and 7th decade
What symptoms do patients usually present with in vasculitis?
fever migratory arthralgia (different joint each day) weight loss anorexia malaise
How is ANCA positive vaculitis diagnosed with investigations?
Urinalysis – blood and protein present
Bloods (raised infl. markers, AKI, anaemia)
Immunology:
ANCA
Anti – MPO and Anti – PR3
Renal Biopsy
Describe the typical phenotype of Granulomatosis with Polyangiitis (GPA)?
Anti-PR3 antibodies
Necrotising granulomatous inflammation
Lung involvement (pulmonary/renal syndrome)
Describe the typical phenotype of Microscopic polyangiitis?
Anti-MPO antibodies
Small vessel vasculitis with NO granulomas
renal / lung / skin / GI / nerves
Describe the phenotype of Eosinophilic Granulomatosis with Polyangiitis?
Associated with asthma and eosinophilia
2/3 have skin involvement
How is an ANCA associated vasculitis treated?
Immunosuppression
Steroids
Cyclophosphamide / Rituximab
Plasma Exchange
Supportive – Dialysis, Ventilation
What are the main parts of the body affected by lupus?
skin joints kidneys lungs nervous system serous membranes
What groups are most likely to develop lupus?
Women in their 20s -30s more commonly affected (10:1)
African Americans, Afro-Caribbean’s and Hispanics
What investigations should you carry out if you suspect lupus?
Bloods:
- Raised infl. markers
Immunology:
- ANA
- anti-dsDNA Ab
- Complement – low levels in flare
Urinalysis
What are the main differentials of SLE?
Sjogren’s syndrome
Fibromyalgia
Primary anti-phospholipid syndrome
Thrombotic micro-angiopathies
What percentage of lupus patients have renal involvement at diagnosis?
50%
What percentage of patients with lupus will have renal disease during the course of their life?
60%
What is the main indicator of lupus neprhitis?
proteinuria
Lupus can cause many different disease processes in the kidney. How do we differentiate which one a patient has developed?
Renal biopsy
How is Lupus nephritis classified?
Class I - minimal mesangial involvement
Class VI - Advanced sclerosing
What can predispose to a poorer prognosis in lupus nephritis?
- male sex
- extremity of age at presentation
- poor socio-economic status
- antiphospholipid syndrome
- high disease activity
