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Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)
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Plasma Cell Dyscrasias & The Kidney (How they affect the kidney? When to suspect? How to diagnose?)

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by dr Mohammed Abdel Gawad (drgawad@gmail.com): Nephrology Specialist at Kidney & Urology Center - Alexandria - Egypt.

by dr Mohammed Abdel Gawad (drgawad@gmail.com): Nephrology Specialist at Kidney & Urology Center - Alexandria - Egypt.

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  • 1. Plasma Cell Dyscrasias & The Kidney Mohammed Abdel Gawad Nephrology Specialist Kidney & Urology Center (KUC) - Alexandria drgawad@gmail.com How they affect the kidney? When to suspect? How to diagnose?
  • 2. Dyscrasias Gamma Globulin Light vs Heavy Chain Monoclonal vs Polyclonal Gammopathy LCDD, HCD D Amyloidosis Multiple Myeloma SPE / Immunofixation Imunotactoid GN Fibrillary GN
  • 3. Plasma Cell Dyscrasias Nephrology Perspectives How they affect the kidney? When to suspect? How to diagnose?
  • 4. Plasma Cells • Plasma cells ultimately originate in the bone marrow; howevaer, these cells leave the bone marrow as B cells, before terminal differentiation into plasma cells normally in lymph nodes. • They are the primary mediators of humoral immunity, secreting antigen-specific immunoglobulins 4 • Fairfax KA, Kallies A, Nutt SL, et al. Semin Immunol. 2008;20:49 • Radbruch A, Muehlinghaus G, Luger EO, et al. Nat Rev Immunol. 2006;6:741-750.
  • 5. Immunoglobulin (Antibody, Gama Globulin) Structure 5 kappa (к) or lambda (λ) IgM, IgA, IgG, IgE, IgD (Some Igs are not gamma globulins, and some gamma globulins are not Igs) Kolitha Basnayake et al. Kidney International (2011) 79, 1289–1301
  • 6. Monoclonal Abs (Ig, Gama Globulin) • Antibodies that are identical because they were produced by one type of B cell. • Detect only one epitope on the antigen. • Antibodies that are non-identical because they were produced by different B cell resources. • Detect multiple epitopes on any one antigen. Polyclonal Abs (Ig, Gama Globulin) 6 • Fairfax KA, Kallies A, Nutt SL, et al. Semin Immunol. 2008;20:49 • Radbruch A, Muehlinghaus G, Luger EO, et al. Nat Rev Immunol. 2006;6:741-750.
  • 7. Plasma Cell Dyscriasis (Clonal proliferation of plasma cells) Monoclonal gammopathy (Paraproteinemia) Excess monoclonal LIGHT chain Mainly Amyloid fibril transformation (fibrils 8-15 nm) AL (primary amyloidosis or Immunotactoid GN (glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits GOMMID) (microtubules >30nm) Mainly LCDD (granular deposits Excess monoclonal HEAVY chain HCDD (granular deposits) HLCDD (granular deposits) Excess monoclonal INTACT Ig IgG, C3, , Fibrillariy Glomerulopathy (fibrilis 12-22 nm) Polyclonal gammopathy Plasma Cells > 10 % Multiple Myeloma < 10% Clonal Cell Proliferation v v v v M. Gawad. www.nephrotube.blogspot.com
  • 8. Plasma Cell Dyscriasis (Clonal proliferation of plasma cells) Monoclonal gammopathy (Paraproteinemia) Excess monoclonal LIGHT chain Mainly Amyloid fibril transformation (fibrils 8-15 nm) AL (primary amyloidosis or Immunotactoid GN (glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits GOMMID) (microtubules >30nm) Mainly LCDD (granular deposits Excess monoclonal HEAVY chain HCDD (granular deposits) HLCDD (granular deposits) Excess monoclonal INTACT Ig IgG, C3, , Fibrillariy Glomerulopathy (fibrilis 12-22 nm) Polyclonal gammopathy Plasma Cells > 10 % Multiple Myeloma < 10% Clonal Cell Proliferation v v v v How they affect the kidney? M. Gawad. www.nephrotube.blogspot.com
  • 9. kappa (к) or lambda (λ) Normally FLCs cleared from the circulation by the kidneys → catabolism in PCT Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 Maack T et al. Kidney Int 1979;16: 251–270. M. Gawad. www.nephrotube.blogspot.com
  • 10. kappa (к) or lambda (λ) Normally FLCs cleared from the circulation by the kidneys → catabolism in PCT Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 Maack T et al. Kidney Int 1979;16: 251–270. Plasma cell proliferation → Overproduction of FLCs → Exceeds the reabsorptive capacity of PTECs M. Gawad. www.nephrotube.blogspot.com
  • 11. kappa (к) or lambda (λ) Normally FLCs cleared from the circulation by the kidneys → catabolism in PCT Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 Maack T et al. Kidney Int 1979;16: 251–270. Plasma cell proliferation → Overproduction of FLCs → Exceeds the reabsorptive capacity of PTECs Transported into the mesangium Pass into tubular ultrafiltrate M. Gawad. www.nephrotube.blogspot.com
  • 12. kappa (к) or lambda (λ) Normally FLCs cleared from the circulation by the kidneys → catabolism in PCT Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 Maack T et al. Kidney Int 1979;16: 251–270. Plasma cell proliferation → Overproduction of FLCs → Exceeds the reabsorptive capacity of PTECs Transported into the mesangium Pass into tubular ultrafiltrate M. Gawad. www.nephrotube.blogspot.com
  • 13. Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301
  • 14. Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 (λ)
  • 15. Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 (λ) (к)
  • 16. Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 organized (fibrillar, crystalline or micro-tubular) → immunotactoid glomerulopathy (λ) (к)
  • 17. Fibrillary, misfolded, nonbranching, -pleated sheet structures (7-12nm) (λ) Antiparallel -Sheets Parallel -Sheets Herrera GA, et al. Ultrastruct Pathol 1999; 23: 107–126. Herrera GA. Ann Diagn Pathol 2000; 4: 174–200. Tennent GA et al. Proc Natl Acad Sci USA 1995; 92: 4299–4303. Scholefield Z et al. J Cell Biol 2003; 163: 97–107. Yamaguchi I et al Kidney Int 2003; 64: 1080–1088. major site in glomeruli, with arterioles, arteries, i nterstitium, and tubular basement membranes involved to lesser degrees.
  • 18. Fibrillary, misfolded, nonbranching, -pleated sheet structures (7-12nm) (λ) Antiparallel -Sheets Parallel -Sheets Serum amyloid protein (SAP) Protects fibrils from proteolytic degradation Glycosaminoglycans (Heparan sulfate) Herrera GA, et al. Ultrastruct Pathol 1999; 23: 107–126. Herrera GA. Ann Diagn Pathol 2000; 4: 174–200. Tennent GA et al. Proc Natl Acad Sci USA 1995; 92: 4299–4303. Scholefield Z et al. J Cell Biol 2003; 163: 97–107. Yamaguchi I et al Kidney Int 2003; 64: 1080–1088. major site in glomeruli, with arterioles, arteries, interstitium, and tubular basement membranes involved to lesser degrees.
  • 19. Fibrillary, misfolded, nonbranching, -pleated sheet structures (7-12nm) (λ) Antiparallel -Sheets Parallel -Sheets Serum amyloid protein (SAP) Protects fibrils from proteolytic degradation Glycosaminoglycans (Heparan sulfate) Primary (AL) Amyloidosis Herrera GA, et al. Ultrastruct Pathol 1999; 23: 107–126. Herrera GA. Ann Diagn Pathol 2000; 4: 174–200. Tennent GA et al. Proc Natl Acad Sci USA 1995; 92: 4299–4303. Scholefield Z et al. J Cell Biol 2003; 163: 97–107. Yamaguchi I et al Kidney Int 2003; 64: 1080–1088. major site in glomeruli, with arterioles, arteries, i nterstitium, and tubular basement membranes involved to lesser degrees.
  • 20. Secondary (AA) Amyloidosis (λ) Primary (AL) Amyloidosis Fibrils are composed of the serum Amyloid A protein. Causes of AA Rheumatoid arthiritis Other arthoropathies: Ankylosing spondylitis, psoriatic arthropathy IBD Chronic suppurative infections: bronchiactesis, osteomyelitis TB, Leprosy Malignancy (RCC, Lynphoma) FMF Novak L et al. Nephrol Dial Transplant 2004;19:3050. Jaccard A. Moreau P, Leblond V, et al. N Engl J Med 2007; 357 (11): 1083–1093.
  • 21. Secondary (AA) Amyloidosis Familial Amyloidosis (λ) Primary (AL) Amyloidosis Fibrils are composed of the serum Amyloid A protein. Fibrils are composed of the mutant protein Novak L et al. Nephrol Dial Transplant 2004;19:3050. Jaccard A. Moreau P, Leblond V, et al. N Engl J Med 2007; 357 (11): 1083–1093.
  • 22. M. Gawad. www.nephrotube.blogspot.com
  • 23. M. Gawad. www.nephrotube.blogspot.com
  • 24. Tubulopathic FLCs Enter the proximal tubule unhindered No receptor uptake on MCs Proximal tubular toxicity/Fanconi syndrome Cast Formation/TIN M. Gawad. www.nephrotube.blogspot.com
  • 25. Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 The classical histological finding is intralysosomal crystalline deposits of FLCs within PTECs
  • 26. Ashley B. Irish . Comprehensive Clinical Nephrology. 4th edition, chapter 63.
  • 27. Cast formation is characteristic for Multiple Myeloma. But it may also be seen in up to a third of cases of LCDD, but is rare in AL amyloidosis Kolitha Basnayake et al. Kidney Int (2011) 79, 1289–1301 Pozzi C et al. Am J Kidney Dis 2003; 42: 1154–1163. Fractured DCT protein precipitates (casts), consisting of uromodulin & FLC Cast is characterized by tubulointerstitial inflammation and fibrosis
  • 28. When to suspect Amyloidosis clinically? Nephrotic syndrome (severe edema, often with anasarca and pleural effusions) Pierre M. Ronco. Comprehensive Clinical Nephrology. 4th edition, chapter 26.
  • 29. When to suspect Amyloidosis clinically? Restrictive cardiomyopathy, conduction abnormalities Hepatomegaly Easy bruising, Factor IX and X deficiency with bleeding Palpable spleen Peripheral neuropathy (carpal tunnel syndrome) Malabsorption, motility disorders Macroglossia Involvement of the adrenal glands can cause primary hypoadrenalism. Pierre M. Ronco. Comprehensive Clinical Nephrology. 4th edition, chapter 26.
  • 30. When to suspect LCDD Clinically? Pierre M. Ronco. Comprehensive Clinical Nephrology. 4th edition, chapter 26.
  • 31. Stepwise Approach - AL Amyloidosis or LCDD Diagnosis? Diagnostic fat pad aspirate from abdomen or rectal mucosal biopsy Pierre M. Ronco. Comprehensive Clinical Nephrology. 4th edition, chapter 26.
  • 32. Pierre M. Ronco. Comprehensive Clinical Nephrology. 4th edition, chapter 26.
  • 33. By electron microscopy, amyloid appears as randomly oriented thin fibrils, 10 to 12 nm in diameter, with a loose, flocculent background (transmission electron microscopy; original magnification x51,250).
  • 34. Plasma Cell Dyscriasis (Clonal proliferation of plasma cells) Monoclonal gammopathy (Paraproteinemia) Excess monoclonal LIGHT chain Mainly Amyloid fibril transformation (fibrils 8-15 nm) AL (primary amyloidosis or Immunotactoid GN (glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits GOMMID) (microtubules >30nm) Mainly LCDD (granular deposits Excess monoclonal HEAVY chain HCDD (granular deposits) HLCDD (granular deposits) Excess monoclonal INTACT Ig IgG, C3, , Fibrillariy Glomerulopathy (fibrilis 12-22 nm) Polyclonal gammopathy Plasma Cells > 10 % Multiple Myeloma < 10% Clonal Cell Proliferation v v v v How they affect the kidney? M. Gawad. www.nephrotube.blogspot.com
  • 35. Plasma Cell Dyscriasis (Clonal proliferation of plasma cells) Monoclonal gammopathy (Paraproteinemia) Excess monoclonal LIGHT chain Mainly Amyloid fibril transformation (fibrils 8-15 nm) AL (primary amyloidosis or Immunotactoid GN (glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits GOMMID) (microtubules >30nm) Mainly LCDD (granular deposits Excess monoclonal HEAVY chain HCDD (granular deposits) HLCDD (granular deposits) Excess monoclonal INTACT Ig IgG, C3, , Fibrillariy Glomerulopathy (fibrilis 12-22 nm) Polyclonal gammopathy Plasma Cells > 10 % Multiple Myeloma < 10% Clonal Cell Proliferation v v v v How they affect the kidney? M. Gawad. www.nephrotube.blogspot.com
  • 36. Plasma Cell Dyscriasis (Clonal proliferation of plasma cells) Monoclonal gammopathy (Paraproteinemia) Excess monoclonal LIGHT chain Mainly Amyloid fibril transformation (fibrils 8-15 nm) AL (primary amyloidosis or Immunotactoid GN (glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits GOMMID) (microtubules >30nm) Mainly LCDD (granular deposits Excess monoclonal HEAVY chain HCDD (granular deposits) HLCDD (granular deposits) Excess monoclonal INTACT Ig IgG, C3, , Fibrillariy Glomerulopathy (fibrilis 12-22 nm) Polyclonal gammopathy Plasma Cells > 10 % Multiple Myeloma < 10% Clonal Cell Proliferation v v v v How they affect the kidney? M. Gawad. www.nephrotube.blogspot.com
  • 37. Plasma Cell Dyscriasis (Clonal proliferation of plasma cells) Monoclonal gammopathy (Paraproteinemia) Excess monoclonal LIGHT chain Mainly Amyloid fibril transformation (fibrils 8-15 nm) AL (primary amyloidosis or Immunotactoid GN (glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits GOMMID) (microtubules >30nm) Mainly LCDD (granular deposits Excess monoclonal HEAVY chain HCDD (granular deposits) HLCDD (granular deposits) Excess monoclonal INTACT Ig IgG, C3, , Fibrillariy Glomerulopathy (fibrilis 12-22 nm) Polyclonal gammopathy Plasma Cells > 10 % Multiple Myeloma < 10% Clonal Cell Proliferation v v v v How they affect the kidney? M. Gawad. www.nephrotube.blogspot.com
  • 38. Plasma Cell Dyscriasis (Clonal proliferation of plasma cells) Monoclonal gammopathy (Paraproteinemia) Excess monoclonal LIGHT chain Mainly Amyloid fibril transformation (fibrils 8-15 nm) AL (primary amyloidosis or Immunotactoid GN (glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits GOMMID) (microtubules >30nm) Mainly LCDD (granular deposits Excess monoclonal HEAVY chain HCDD (granular deposits) HLCDD ( or ) (granular deposits) Excess monoclonal INTACT Ig IgG, C3, , Fibrillariy Glomerulopathy (fibrilis 12-22 nm) Polyclonal gammopathy Plasma Cells > 10 % Multiple Myeloma < 10% Clonal Cell Proliferation v v v v How they affect the kidney? M. Gawad. www.nephrotube.blogspot.com
  • 39. Plasma Cell Dyscriasis (Clonal proliferation of plasma cells) Monoclonal gammopathy (Paraproteinemia) Excess monoclonal LIGHT chain Mainly Amyloid fibril transformation (fibrils 8-15 nm) AL (primary amyloidosis or Immunotactoid GN (glomerulonephritis with organized monoclonal microtubular immunoglobulin deposits GOMMID) (microtubules >30nm) Mainly LCDD (granular deposits Excess monoclonal HEAVY chain HCDD (granular deposits) HLCDD ( or ) (granular deposits) Excess monoclonal INTACT Ig IgG, C3, , Fibrillariy Glomerulopathy (fibrilis 12-22 nm) Polyclonal gammopathy Plasma Cells > 10 % Multiple Myeloma < 10% Clonal Cell Proliferation v v v v How they affect the kidney? M. Gawad. www.nephrotube.blogspot.com
  • 40. What is Multiple Myeloma? Excess of bone marrow–derived plasma cells Dysregulated overproduction of a monoclonal Ig (the paraprotein or M- protein) Associated light chains (kappa and lambda) Leung N et al. Am J Kidney Dis 2004;43:147. Pozzi C et al. Am J Kidney Dis 2003;42:1154.
  • 41. MGUS Smouldering (asymptomatic) myeloma Active (symptomatic) myeloma Serum M- protein <3 g/100ml 3 g/100ml 3 g/100ml Bone marrow clonal plasma cells <10% 10% 10% or Plasmacytoma Related organ or tissue impairment Absent and No evidence of other B-cell proliferative disorders Absent/ Asyptomatic Requires 1 or more of the following: • Calcium elevation • Renal insufficiency • Anaemia • Bone osteolytic lesion International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121:749-757. When to suspect Multiple Myeloma?
  • 42. Serum protein electrophoresis (SPE) Serum immunofixation electrophoresis (sIFE) Can detect the whole immunoglobulin (cannot reliably differentiate monoclonal from polyclonal light chain expansion) 10 times more sensitive for immunoglobulins Only detects increased LC in patients who have very high levels of LC-only myeloma 10 times more sensitive for LC Semi-quantitative Not quantitative Laboratory Diagnostic Tests Katzmann JA et al. Clin Chem. 2002;48(9):1437-1444.
  • 43. Ashley B. Irish . Comprehensive Clinical Nephrology. 4th edition, chapter 63.
  • 44. Serum protein electrophoresis (SPE) Paraprotein is a monoclonal Ig (gamma globulin) that is produced in excess by the clonal proliferation of plasma cells. 45Katzmann JA et al. Electrophoresis. 1997;18:1775-1780.
  • 45. Serum protein electrophoresis (SPE) Paraprotein is a monoclonal Ig (gamma globulin) that is produced in excess by the clonal proliferation of plasma cells.
  • 46. Urine PEP, immunofixation electrophoresis (uIFS) (to detect Bence Jones Proteinuria) Serum SPEP, immunofixation electrophoresis (sIFE) • Can detect low levels of LC • Yet remains less sensitive than sFLC measurement because sFLC are elevated before urine overflow may occur. More sensitive Laboratory Diagnostic Tests Dr. Henry Bence-Jones 31 December 1813 / / April 20, 1873
  • 47. By Nephelometry Rapid (hours), More sensitive (1–3 mg/L) along with an SPE will diagnose the majority of patients with myeloma, amyloidosis, and other MIDD. Serum Free Light Chains (к and λ) Measurement Normal к/λ CKD к/λ Abnormal к/λ ratio 0.26–1.65 0.37–3.17 Significant accumulation of sFLC occurs (approximately five-fold) Occurs as a result of overproduction of a single к or λ clone Katzmann JA et al. Clin Chem. 2002;48(9):1437-1444. Lachmann HJ et al. Br J Haematol. 2003;122(1):78-84.
  • 48. By Nephelometry Rapid (hours), More sensitive (1–3 mg/L) along with an SPE will diagnose the majority of patients with myeloma, amyloidosis, and other MIDD. Serum Free Light Chains (к and λ) Measurement Normal к/λ CKD к/λ Abnormal к/λ ratio 0.26–1.65 0.37–3.17 Significant accumulation of sFLC occurs (approximately five-fold) Occurs as a result of overproduction of a single к or λ clone This excess is detectable in the serum before urinary tubular catabolism is exceeded and before the SPE or IFE is abnormal Katzmann JA et al. Clin Chem. 2002;48(9):1437-1444. Lachmann HJ et al. Br J Haematol. 2003;122(1):78-84.
  • 49. By Nephelometry Rapid (hours), More sensitive (1–3 mg/L) along with an SPE will diagnose the majority of patients with myeloma, amyloidosis, and other MIDD. Serum Free Light Chains (к and λ) Measurement Normal к/λ CKD к/λ Abnormal к/λ ratio 0.26–1.65 0.37–3.17 Significant accumulation of sFLC occurs (approximately five-fold) Occurs as a result of overproduction of a single к or λ clone This excess is detectable in the serum before urinary tubular catabolism is exceeded and before the SPE or IFE is abnormal Katzmann JA et al. Clin Chem. 2002;48(9):1437-1444. Lachmann HJ et al. Br J Haematol. 2003;122(1):78-84. This excess is detectable in the serum in MIDD, amyloid, or “nonsecretory” myeloma, in whom no monoclonal Ig has been identified with electrophoretic techniques.
  • 50. How Multiple Myeloma affect the Kidney? Acute tubular necrosis (10%) Toxic injury/ Fanconi syndrome Myeloma cast nephropathy (30-50%) Urate nephropathy, Hyper calcemia (5%) precipitated by sepsis or hypotension Interstitial nephritis/fibrosis without cast nephropathy (20%-30%) Ashley B. Irish . Comprehensive Clinical Nephrology. 4th edition, chapter 63. Korbet SM. J Am Soc Nephrol 2006;17:2533. San Miguel JF et al. N Engl J Med 2008;359 (9): 906–917.
  • 51. Renal Pathology in Patients with Multiple Myeloma Ashley B. Irish . Comprehensive Clinical Nephrology. 4th edition, chapter 63.
  • 52. Ashley B. Irish . Comprehensive Clinical Nephrology. 4th edition, chapter 63.
  • 53. Clinical Tips & Tricks Diagnosis of Multiple Myeloma Urine Analysis Patient with renal impairment and lower limb edema
  • 54. Clinical Tips & Tricks Diagnosis of Multiple Myeloma Urine Analysis Patient with renal impairment and lower limb edema In Myeloma: increased urinary excretion of light chains Not detected by dipstick
  • 55. Clinical Tips & Tricks Diagnosis of Multiple Myeloma Urine Analysis Patient with renal impairment and lower limb edema In Myeloma: increased urinary excretion of light chains Not detected by dipstick Total protein quantification or specific urine electrophoresis & immunofixation.
  • 56. Clinical Tips & Tricks Diagnosis of Multiple Myeloma Pseudo-Hyponatremia Na is here
  • 57. Clinical Tips & Tricks Diagnosis of Multiple Myeloma Pseudo-Hyponatremia Na is here Flame photometry measure Na in relation to all compartments
  • 58. Clinical Tips & Tricks Diagnosis of Multiple Myeloma Pseudo-Hyponatremia Na is here Flame photometry measure Na in relation to all compartments
  • 59. Clinical Tips & Tricks Diagnosis of Multiple Myeloma Pseudo-Hyponatremia Serum Na x 93 99 – 1.03 (triglyceride gm/L) – 0.73 (protein gm/L) Corrected Na =
  • 60. Clinical Tips & Tricks Diagnosis of Multiple Myeloma Pseudo-Hyponatremia Therefore, for patients with marked elevations in plasma lipids or plasma proteins, ask the hospital laboratory to use an ion-specific electrode to measure the plasma sodium concentration.
  • 61. A diagnosis of a plasma cell dyscrasia is not always known prior to the discovery of abnormal kidney function. The renal biopsy, performed to identify the responsible lesion, is not infrequently the initial indication of a plasma cell dyscrasia. Durie BG et al. Hematol J 2003;4:379. Herrera GA et al. Arch Pathol Lab Med 2004;128:875.
  • 62. www.nephrotube.blogspot.com h facebook group: NephroTube Mohammed Abdel Gawad drgawad@gmail.com

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