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Indications for Plasmapheresis

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Title: 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)

11
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

17
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

18
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

19
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?

23
(1.5 x HF BFR)
(0.4 x citrate rate)
24
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
25
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)
26
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

27
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

28
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

29
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.

31
Indication of TPECategory 4 Lack of efficacy
in controlled trials.
  • Examples AIDS, amyotrophic lateral sclerosis,
    lupus nephritis, psoriasis, renal transplant
    rejection, schizophrenia, rheumatoid arthritis

32
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?

33
Meta-analysis
34
Acknowledgement
  • Thanks to Pat Brophy and Stuart Goldstein for
    many of these slides and thought processes
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