MYELOMA AND THE KIDNEY

1
MYELOMA AND THE KIDNEY

• DIAGNOSIS
• TREATMENT
• PROGNOSIS

2
MYELOMA

• Monoclonal expansion of plasma cell population
• Incidence 5 per 100,000
• Median age 69 male, 71 female
• 5 lt40 years at diagnosis 10-15 lt50 years

3
Diagnostic Criteria 1

• MAJOR
• plasmacytoma on tissue biopsy
• bone marrow plasmacytosis gt30
• monoclonal globulin elevation on electrophoresis
  
  
• gt35 g/l for IgG
  
  
  
• gt20 g/l for IgA
• gt1 g/ 24hrs of kappa/lambda light chains in
  urine

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Diagnostic Criteria 2

• MINOR
• bone marrow plasmacytosis 10-30
• monoclonal globulin elevation (lt major)
• lytic bone lesions
• immune paresis
• DIAGNOSIS 1 major 1 minor

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Staging

• Durie Salmon Cancer 1975
• 1. Low myeloma mass
  Hb gt10g/l Ca normal 1 or less
  osteolytic lesions
• 2. Intermediate (fits neither 1. nor 2.)
• 3. High myeloma mass
  Hb lt8.5g/l Ca elevated multiple
  osteolytic lesions

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Prevalence of Renal Failure 1

• Knusden Eur. J. Haem. 2000
• 775 myeloma patients 1984-86, 1990-92
• 29 had creatinine gt130
• 58 achieved normal creatinine in 1 year
• recovery more likely if
• moderate ARF, hypercalcaemia low BJP mass

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Prevalence of Renal Failure 2

• in multivariate analysis independent prognostic
  factors for survival
• renal failure
• age
• stage 3 disease
• hypercalcaemia
• median survival of those dialysed 3.5 months

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Prevalence of Renal Failure 3

• MRC Myeloma Trial, BMJ, 1994
• 998 patients under 75 years
• 1982-91
• 43 creatinine gt130

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Renal Disease in Myeloma

• Myeloma Kidney or Cast Nephropathy
• Renal Tubular Dysfunction
• Amyloidosis
• Cryoglobulinaemia
• Hypercalcaemia
• ARF with radiocontrast agents

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Immunoglobulin light chains (or Bence-Jones
proteins) 1

• kappa or lambda
• molecular weight 22,000
• freely filtered in glomeruli
• normal rate lt30mg/day of light chain excretion
• re-absorbed in proximal tubule
• not detected by urinary dipstick
• bind to Tamm-Horsfall mucoprotein
• in myeloma 100mg-30 g/day

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Immunoglobulin light chains (or Bence-Jones
proteins) 2

• Direct tubular toxicity
• Intra-tubular cast formation and obstruction
• Variable nephrotoxic potential (cast nephropathy,
  amyloidosis, no renal disease)

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Myeloma Kidney

• acute or chronic renal failure that results from
  the filtration of monoclonal immunoglobulin light
  chains
• tubular toxicity
• intra-tubular cast formation and obstruction

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TREATMENT

• Rehydration
• Urine Alkalinisation
• Loop Diuretics
• Chemotherapy
• Plasmapheresis
• Dialysis

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Rehydration

• isotonic solutions
• hypercalcaemia
• contrast examinations
• treat infection stop nephrotoxins

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Urine Alkalinisation

• Huang, Lab. Invest. 1993
• Tamm-Horsfall solubility reduced at low pH
• acidic environment increases light-chain/THMP
  binding
• forced alkaline diuresis gt3 l/day with urinary pH
  gt7

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Loop Diuretics

• may have a role if hypercalcaemia present
• wash out obstructing casts
• Sanders, J. Clin. Invest. 1992
• in rats diuretics increase tubular Na conc..
  which promotes THMP aggregation

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Chemotherapy

• to reduce light-chain production
• melphalan, cyclophosphamide, steroids
• VAD (vincristine, doxorubicin)
• myeloablation with autologous BMT or blood
  stem-cell transplant
• response rate similar whether renal failure or
  not

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Plasmapheresis 1

• effective in rapidly reducing serum light-chain
  load
• no effect on light-chain production
• short-acting as light-chains throughout ECF
• efficacy not fully established

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Plasmapheresis 2

• Johnson Arch. Int. Med. 1990
• prospective , randomised trial of plasmapheresis
• 21 patients with active myeloma renal failure
• all had renal biopsy
• 10- alkaline diuresis, chemotherapy
• 11- alkaline diuresis, chemo, plasmapheresis

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Plasmapheresis 3

• 5 patients on dialysis, 3 recovered renal
  function all of whom had TPE
• 16 non-dialysis patients, 5 in first group and 7
  in second group showed improvement in renal
  function

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Plasmapheresis 4

• Zucchelli, K.I. 1988
• prospective , randomised trial
• 29 patients, BJP gt1g/day
• 24 required RRT
• 15- chemo, plasmapheresis, /- HD
• 14- chemo, /- PD

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Plasmapheresis 5

• Group 1
• 13/15 recovered renal function
• 68 1 year survival
• Group 2
• 2/14 recovered renal function
• 28 1 year survival
• 5 deaths before 2 months

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Renal Replacement Therapy

• No trials comparing PD/HD
• both modalities remove small amount of
  light-chains

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Renal Replacement Therapy

• Korzets, Am. J. Kid. Dis. 1990
• 10 patients with myeloma ESRF (all on PD)
• Survival
• from diagnosis- 32/- 24 months
• from start RRT- 25/- 20 months
• 5 responded to chemo- 47/- 25 months
• 5 non-responders- 17/- 7 months

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Renal Replacement Therapy

• Iggo, Q. J. Med. 1989
• 23 patients, 11 presented with ESRF
• 15 died during study
• actuarial survival 45 at 1 year
• 6 still alive at 2 years
• HD/PD equally effective
• peritonitis a common problem

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Outcomes and Prognosis 1

• Rota, Medicine 1987
• 34 patients, myeloma creatinine gt300
• 16 recovered renal function
• 18 did not, 9 required dialysis
• fewer females recovered
• 88 had biopsy recovery only if ATN or typical
  cast nephropathy
• recovery may be delayed (months)

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Outcomes and Prognosis 2

• 6 further studies
• 151 patients
• renal recovery 51 (mean 17-83)
• median survival 17 months (9-22)
• Alexanian, Arch. Int. Med.. 1990
• 494 consecutive myeloma patients
• presence/degree renal failure not predictive for
  survival

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Outcomes and Prognosis 3

• Clark Blood Rev. 1999
• renal impairment present in 50
• dialysis now accepted treatment (ARF CRF)
• renal failure not a contra-indication to
  aggressive treatment (autologous BMT stem-cell
  transplant)
• outcome similar to those without renal impairment