Myeloma and the Kidney Ryan Sanford 2.22.2010. How Often is the Kidney Involved Symptomatic MM: CRAB...
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Transcript of Myeloma and the Kidney Ryan Sanford 2.22.2010. How Often is the Kidney Involved Symptomatic MM: CRAB...
Myeloma and the Kidney
Ryan Sanford2.22.2010
How Often is the Kidney Involved
Symptomatic MM: CRAB– hyperCalcemia– Renal dysfunction– Anemia– Bone lesions
1/5 to 2/5 patients with MM have renal involvement
What Does it Signify?
At presentation– SCr < 1.5 80% alive at 1 year– SCr > 2.3 50% alive at 1 year
Renal Improvement to MM Treatment also favorable
The Immunoglobulin
Light Chains come in lambda and kappa
A Few General Points First
The Proteins of MM– Light chains (LC) almost always the problem– Various potential proteins to be produced
Intact immunoglobulins +/- Light Chains and Heavy Chains
The SPEP: – Not a good test to identify LCs– Increased sensitivity if coupled with serum immunofixation– Can only quantify LCs with direct assessment
The UPEP– Prior to serum free light chain assessment, the UPEP was the test
of choice to find LCs
The Light Chain (LC)
aka Bence Jones proteins– Monoclonal– A ratio of κ:λ
Freely filtered, absorbed in PCT The LC biochemical properties determines
the type, if any, of renal disease
The Serum Free Light Chain Assessment
Polyclonal ABs directed at hidden LC epitopes (when a full Ig) used for sensitive quantification of κ and λ light chains
Coupled with SPEP more Sn/Sp than SPEP/UPEP
Could be replacing UPEP as test of choice
What Types of Involvement
Light chain cast nephropathy – Myeloma Kidney [>40% of cases]
Light chain deposition disease [<10%] Primary AL Amyloidosis [<10%] Also: Hypercalcemia, interstitial nephritis,
acquired Fanconi’s syndrome, GN
Proteinuria in MM
Albuminuria [a grossly positive U/a for protein]– If positive:
Nonspecfic glomerular leak, nephrosis LCDD or Amyloidosis
– If negative: other proteins or no protein in urine; cast nephropathy
Addition of Sulfosalicylic Acid to Supernatant– If bland sediment and minimal protein on U/a– Precipitates all urinary protein– If positive suggestive of light chains in urine
Cast Nephropathy / Myeloma Kidney
Acute or Chronic Worsened by volume depletion Two mechanisms
– Intratubular casts and obstruction LC has affinity for Tamm-Horsfall protein (secreted in
thick AL) See casts in distal nephron
– Direct tubular toxicity U/a: trace/no protein; bland sediment
With the Microscope
LC Cast with Obstruction
Treatment of Cast Nephropathy
Chemotherapy to reduce LC production Aggressive hydration Plasmapheresis?
– Rapid removal of toxic LC– Contentious– If beneficial – best for those with high levels of
LCs, severe renal failure, and firm diagnosis of cast nephropathy
AL Amyloidosis
LC uptake, processing, and secretion by macrophages
Secretion product precipitates into β-pleated fibrils, becoming Congophilic
Nephrosis and progressive loss of GFR
Light Chain Deposition Disease
Similar to AL Amyloidosis, except no fibril formation of Congophilic staining
Nephrosis and progressive loss of GFR
Tubular Malfunction
LCs reabsorbed in PCT and accumulate– Fanconi Syndrome
Phosphate wasting Proximal RTA [type 2] Hypouricemia Glycosuria Proteinuria Hypokalemia and hypochloremia
References
UpToDate.com Hutchison, C.A. et al. Nat Rev Nephrol.
Serum free light chain assessment in monoclonal gammopathy and kidney disease. 5, 621-627 (2009)