Myeloma Flashcards
What is myeloma kidney?
-Characteristic cast nephropathy that can occur when light chains are circulating (and filtered at the glomerulus) at high level.
=Cast nephropathy is just one way that myeloma can affect the kidney.
-But even without overt myeloma, overproduction of monoclonal immunoglobulins can affect the kidney in a number of ways – sometimes called MGRS, Monoclonal Gammopathy of Renal Significance, to distinguish it from MGUS, (of Unknown significance).
What is multiple myeloma?
Multiple myeloma (MM) is a haematological malignancy characterised by plasma cell proliferation. It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells
Features of multiple myeloma
-Median age at presentation 70
CRABBI
-Calcium, hypercalcaemia
=primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
=much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels
=this leads to constipation, nausea, anorexia and confusion
-Renal
=monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
=this causes renal damage which presents as dehydration and increasing thirst
=other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
-Anaemia
=bone marrow crowding suppresses erythropoiesis leading to anaemia
=this causes fatigue and pallor
-Bleeding
=bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
-Bones
=bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
=this may present as pain (especially in the back) and increases the risk of pathological fractures
-Infection
=a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
Other features include
=amyloidosis e.g. macroglossia
=carpal tunnel syndrome
=neuropathy
=hyperviscosity
How does myeloma affect the kidneys?
-Cast nephropathy – some light chains may aggregate. An interstitial problem.
-AL amyloidosis – usually causes nephrotic syndrome.
-Hypercalcaemia – the myeloma causes it, and the hypercalcaemia affects kidney function.
-Tumour lysis syndrome with acute urate crystal nephropathy – usually after chemotherapy causing cell death; prevent by pre-treatment with allopurinol.
What is MGUS?
-Monoclonal Gammopathy of Unknown Significance, reflects overgrowth of a B cell clone producing a clonal immunoglobulin.
-It can be regarded as a benign neoplasm.
-It becomes increasingly common with age, and in older age groups is so common that it is frequently found coincidentally in association with other pathologies.
-It has a transformation rate to overt myeloma of approx 1% per year – so never gets there in most.
What is MGRS?
MGRS (MG of Renal significance): some light chains can cause disease without transformation to myeloma.
=AL amyloidosis – sometimes this occurs without triggering criteria for overt myeloma.
=Light chain deposition disease; typically nephrotic syndrome from GBM (and elsewhere) deposition of light chains – different from AL amyloid.
=Disease caused by deposition of other Ig fragments, e.g. Heavy chain deposition disease.
=Proximal tubulopathy and renal Fanconi syndrome associated with light chain crystal formation in proximal tubules.
=Interstititial renal disease without crystals or casts – may be contentious.
=Various monoclonal immunoglobulin deposition diseases, usually glomerular.
Treatment and prognosis of B cell disorders
-Generally the medium to long-term prognosis is determined by whether it is possible to reduce or cease the production of the overproduced light chain or Ig fragment, by chemotherapy or stem cell transplant.
-Cast nephropathy is associated with high levels of light chain production, and typically high tumour loads, so historically, poor prognosis. Modern treatments for myeloma have improved the outlook for myeloma, so that response to treatment is now a dominant influence on prognosis
Investigation in myeloma
-Bloods
=full blood count: anaemia (bone marrow disorder)
=peripheral blood film: rouleaux formation
=urea and electrolytes: renal failure
=bone profile: hypercalcaemia (should be ow in acute renal failure)
-Protein electrophoresis
=raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
in the urine, they are known as Bence Jones proteins
=Protein in urine
=May react poorly with sticks; much lower ACR than PCR (protein creatinine ratio)
=Bence Jones protein detected immunologically
-Kappa/Lambda ratio
-Bone marrow aspiration
=confirms the diagnosis if the number of plasma cells is significantly raised
-Imaging
=historically a skeletal survey has been done to look for bone lesions
=however, whole-body MRI is increasingly used and is now recommended in the 2016 NICE guidelines
=X-rays: ‘rain-drop skull’ (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots). =Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - ‘pepperpot skull’
=Congo red stain= amyloid
Diagnostic criteria for multiple myeloma
The diagnostic criteria for multiple myeloma requires one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma.
Major criteria
Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
30% plasma cells in a bone marrow sample
Elevated levels of M protein in the blood or urine
Minor criteria
10% to 30% plasma cells in a bone marrow sample.
Minor elevations in the level of M protein in the blood or urine.
Osteolytic lesions (as demonstrated on imaging studies).
Low levels of antibodies (not produced by the cancer cells) in the blood.
