B cell disorders and the kidney: Myeloma kidney and more. 20 mins.
Neil Turner, Professor of Nephrology. Part of Renal Medicine in the Edinburgh MBChB.
Myeloma kidney usually means the 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).
How much do I need to know? Undergrads in medicine should be able to describe Myeloma, and an outline of AL amyloidosis. Also know differential diagnosis of, and how to investigate and treat hypercalcaemia. Knowing that MGRS exists would be a bonus.
Myeloma and the Kidney
Key ways myeloma affects the kidney:
- 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.
Beyond these 4, the print gets smaller. The video (12 mins) illustrates the main two renal pictures and gives some more detail.
The Ig molecule and the kidney. 4.15 Cast nephropathy; 5:45 tests in myeloma;
10:45 light chains and the glomulus (amyloid). Text alternative
MGUS, MGRS, and low-level paraprotein effects
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.
However some light chains can cause disease without transformation to myeloma. This is now sometimes called an MGRS (MG of Renal significance). Examples include (note that beyond the first, it is specialist-level stuff):
- 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 – learn about that in Haematology.
Further information
- Interstitial nephritis more broadly (MedCal, 30 mins)
- Glomerular diseases spectrum
- Proteinuric diseases and nephrotic syndrome (includes Amyloidosis)
- Systemic diseases and the kidney(to follow).
- Dr Huw Roddie on Myeloma (video, 12 mins) from Edinburgh Haematology
- Patient information about myeloma kidney (needed; to follow)
- Hypercalcaemia and the kidney (MedCal) – hypercalcaemia with a renal slant.
- Hypercalcaemia …
- Antibodies (Wikipedia) – lengthy, good.
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