Indications for Plasmapheresis

1
Indications for Plasmapheresis
Timothy E. BunchmanPediatric Nephrology
Transplantation
2
Mechanical Removal of Antibodies

• When antibody is rapidly and massively decreased
  by TPE, antibody synthesis increases rapidly.
• This rebound response complicates treatment of
  autoimmune diseases.
• It is usually combined with immune suppressive
  therapy.

3
Goodpastures Syndrome

• Anti-glomerular Basement Membrane Antibody
  Mediated Disease
• Single CT (Johnson et al. Medicine 1985), case
  studies
• TPE useful in rapid lowering of Anti-GBM Ab
• Lower post-treatment serum creatinine, decreased
  incidence of ESRD
• NEED ADJUNCT IMMUNOSUPPRESSIVE REGIMEN
• Follow antibody levels for end point

4
Rapidly Progressive GN (non Anti-GBM)

• RPGN- most patients have evidence of antibody
  associated disease (ANCA), or known immune
  complex disease - IgA, Cryoglobulinemia,lupus
• Case reports (favorable), CT-no favorable
  generalized benefit (Cole et al. 1992, AJKD)
  (when TPE added to standard immunosuppressive
  therapy)

5
Rapidly Progressive GN (non Anti-GBM)

• However
• Subset analysis revealed that TPE was beneficial
  for patients with severe disease or those
  requiring dialysis (Kaplan Ther Apheresis, 1997)

6
Multiple Myeloma with Renal Failure

• Cast Nephropathy resulting from light chain
  toxicity
• TPE in conjunction with proper anti neoplastic
  regimen improves on a more likely return of renal
  function
• Evidence CT (n29) (Zucchelli et al. KI, 1988)-
  strong support
• Recommend- 5 consecutive daily TPE
  treatments-early in course

7
Multiple Myeloma with Renal Failure

• Caveats
• Must rule out other causes of renal failure as
  these patients tend to be relatively ill
• If renal failure well established- results not as
  good- better before onset of oligoanuria (Johnson
  et al. Arch Intern med, 1990)

8
IgA Nephropathy Henoch Schonlein Purpura

• 10 of IgA presents as RPGN
• TPE rationale--removal of circulating IgA
• Evidence No CTs, case reports Treatment /- other
  immunosuppressive agents
• Recommend
• Useful in RPGN presentation (Coppo et al. Plasma
  Ther Transfus Technol, 1985)
• Likely minimal role in chronic disease

9
HSP(Hattori et al, Am J Kid Dis, 1999, 33427-33)

• 9 children with RPGN with HSP Rx with PP without
  immunosuppression
• Proteinuria 4.9 gms/m2
• GFR 46 mls/min/1.73 m2
• 6/9 complete recovery
• 2/9 rebound with proteinuria with progression to
  ESRD

10
Cryoglobulinemia

• Renal Manifestations- glomerular capillary
  deposition of cryoglobulin or immune complex
  disease with complement activation and vasculitis
• Evidence No CTs, case reports and uncontrolled
  trials
• Consensus Useful adjunct in treatment of severe
  disease (progressive RF, coalescing purpura,
  advanced neuropathy) (DAmico et al. KI, 1989)

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Cryoglobulinemia

• Caveat
• If Hep C associated disease interferon-alpha used
  as treatment (Misiani et al. NEJM, 1994)
• Can use TPE as adjunct if disease reappears after
  discontinuing interferon in immediate period when
  considering reintroduction of interferon

12
Hemolytic Uremic Syndrome

• Difficult at times to differentiate between TTP
  and HUS (TTP tends to have more neurological
  manifestations while renal failure predominates
  in HUS)
• May be HUS associated with Shiga toxin,
  congenital (factor H deficiency) or caused by
  inciting drugs-cyclosporine, tacrolimus, quinine,
  Oral Contraceptives, or other diseases like SLE
  and carcinoma)

13
Hemolytic Uremic Syndrome

• Evidence- limited-works in TTP? Why not HUS-adult
  outcome usually worse
• SUBGROUPS
• Recurrent HUS in renal Transplantation- (Agarwal
  et al. JASN, 1995) Reviewed case reports- suggest
  TPE effective but endpoint unclear (ie continue
  until renal function returns)
• HUS in Children- No RCTs, case reports suggest
  benefit of limiting renal damage in children with
  no diarrheal prodrome, neurologic manifestations
  or those 5 yrs of age (Gianviti et al. AJKD,
  1993)
• Recommend Minimal data to support use except in
  subgroups above

14
Systemic Lupus Erythematosus

• Evidence- early case reports suggested some
  benefit but CTs have not supported TPE when added
  to standard Immunosuppression (Lewis et al.,
  NEJM, 1992)
• May be some role in pregnancy when use of
  cytotoxic agents are not desired
• ? Treatment refractory disease
• Recommend no evidence to support use

15
Antiphospholipid Antibody Syndrome,
Anticardiolipin Antibodies, Lupus anticoagulant

• Associated with venous arterial thrombosis,
  fetal loss and occasional renal disease
• Evidence- no CTs, case reports
• Limited in renal disease- some benefit noted in
  patients treated for LA pregnancy associated
  thrombotic microangiopathy (Farrugia et al., AJKD
  1992)
• Recommend May be useful when other interventions
  have failed

16
Scleroderma

• Scleroderma with ANCA positive patients, normal
  renin levels, normotensive associated renal
  disease
• Evidence No CTs, case reports (2)
• Seemed to offer clinical improvement (Omote et
  al., Inter Med, 1997)
• Recommend Consideration if poor disease control
  and patient ANCA positive

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Focal Segmental Glomerulosclerosis

• Group Recurrence Post-transplant (15-55
  recurrence)- thought to be due to a circulating
  factor not yet specifically isolated
• Evidence - strong no CTs, case reports with
  clinical and proteinuria improvement (Artero et
  al., AJKD, 1994)
• Recommend Daily therapy (early) for up to 2 weeks

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Focal Segmental Glomerulosclerosis

• Group Native FSGS
• Multiple etiologies, therefore need to evaluate
  carefully
• Evidence equivocal- may offer benefit in
  treatment resistant forms of primary FSGS
• Recommend Clinically based

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Panel Reactive Antibody Reduction

• Transplant Candidates with high titers of
  cytotoxic antibodies- high rate of hyperacute
  rejection of transplanted grafts
• Other therapies also offered-ie monthly IVIG
  infusions-currently undergoing trials
• Evidence used immunoadsorption column
  treatments- No CTs, some encouraging results in
  several case studies (Ross et al.,
  Transplantation, 1993)
• Recommend High consideration in those unable to
  receive renal transplants due to elevated PRA

20
Acute Renal Vascular Rejection

• Evidence 2 controlled trials no significant
  benefit noted (Allen et al., Transplantation,
  1983)
• Recommend No supportive evidence for TPE in this
  treatment

21
Acute Hepatic Failure(Singer et al, Ann Surg,
2001 234418-24)

• 49 children with FHF Rx with PP for
• Hepatic support for recovery/bridge to Tx
• Correction of coagulation
• Results
• 3/49 (8) complete recovery
• 32/49 (64) bridge to Tx
• 14/49 (28) died due to FHF
• No complications from PP

22
PP with or without HF in Sepsis

• New generation of HF machines now have capability
  for PP
• Can be done simultaneously with HF with all
  current machinery
• Does data exist in this area?

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(1.5 x HF BFR)
(0.4 x citrate rate)
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HF Plasma filtration adsorption

• 10 pts with SS
• 10 hrs of PFA CVVHD vs CVVHD alone
• MAP with PFA (p 0.001)
• 11.8 vs 5.5 mmHg
• Norepi
• 0.08 vs 0.005
• TNF alpha production with PFA (p 0.009)

Ronco et al CCM 2002 301387-8
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Plasma exchange and sepsis

• 76 adult pts with DIC/MOSF/ARF-66
• Ventilated-72
• Shock-88
• Rx with PE until DIC reversed
• Avg 2 (range 1-14)
• Predicted mortality rate 80 with Survival rate
  82

(Stegmayr et al CCM 2003 311730-6)
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Sepsis Rx with PE

• Tetta C et al
• Nephrol Dial Transpl 1998 131458-64
• Use of sorbent adsorption for cytokine removal
• Nguyen el al Ped CCM 2001 2187-196
• Rx with PE for Rx of microvascular thrombosis

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Sepsis Rx with PE

• Winchester et al Blood Purif 2179-84
• Use of target sorbents
• Tetta el al
• Ther Apher 2002 109-15
• Int Care Med 2003 291222-8
• Artif Organs 2003 27202-13
• Sorbents, adsorption, PE

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Indication of TPECategory 1 Standard
acceptable therapy

• Chronic idiopathic demyelinating polyneuropathy
  (CIDP), cryoglobulinemia, Goodpastures syndrome,
  Guillain-Barre syndrome, focal segmental
  glomerulonephritis, hyperviscosity, myasthenia
  gravis, post transfusion purpura, Refsums
  disease, TTP

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Indication of TPECategory 2 Sufficient evidence
to suggest efficacy usually as adjunctive therapy

• ABO incompatible organ transplant, bullous
  pemphigoid, coagulation factor inhibitors, drug
  overdose and poisoning (protein bound),
  Eaton-Lambert syndrome, HUS, monoclonal
  gammopahty of undetermined significance with
  neuropathy, pediatric autoimmune neuropsychiatric
  disorder associated with streptococcus, RPGN,
  systemic vasculitis

30
Indication of TPECategory 3 Inconclusive
evidence of efficacy or uncertain risk/benefit
ratio.

• TPE can be considered for the following
  occasions
• Standard therapies have failed.
• Disease is active or progressive.
• There is a marker to follow.
• It is agreed that it is a trial of TPE and when
  to stop.
• Possibility of no efficacy is understood by the
  patient.

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Indication of TPECategory 4 Lack of efficacy
in controlled trials.

• Examples AIDS, amyotrophic lateral sclerosis,
  lupus nephritis, psoriasis, renal transplant
  rejection, schizophrenia, rheumatoid arthritis

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Risk Benefit ratios

• Difficulty of basing all decision on patient care
  on controlled trial data (retrospective or
  prospective) is that one will not advance thought
  process
• If the therapy has known and controlled risks and
  is safe then do not the potential benefits
  potentially out weigh the risks?

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Meta-analysis
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Acknowledgement

• Thanks to Pat Brophy and Stuart Goldstein for
  many of these slides and thought processes