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Myeloma and the Kidney

Myeloma and the Kidney. Ryan Sanford 2.22.2010. 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

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Myeloma and the Kidney

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  1. Myeloma and the Kidney Ryan Sanford 2.22.2010

  2. 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

  3. 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

  4. The Immunoglobulin • Light Chains come in lambda and kappa

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. With the Microscope LC Cast with Obstruction

  12. 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

  13. AL Amyloidosis • LC uptake, processing, and secretion by macrophages • Secretion product precipitates into β-pleated fibrils, becoming Congophilic • Nephrosis and progressive loss of GFR

  14. Light Chain Deposition Disease • Similar to AL Amyloidosis, except no fibril formation of Congophilic staining • Nephrosis and progressive loss of GFR

  15. Tubular Malfunction • LCs reabsorbed in PCT and accumulate • Fanconi Syndrome • Phosphate wasting • Proximal RTA [type 2] • Hypouricemia • Glycosuria • Proteinuria • Hypokalemia and hypochloremia

  16. 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)

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