Presentation on theme: "Indications for Plasmapheresis"— Presentation transcript:
1Indications for Plasmapheresis Timothy E. Bunchman Pediatric Nephrology & Transplantation
2Mechanical 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.
3Goodpasture’s Syndrome Anti-glomerular Basement Membrane Antibody Mediated DiseaseSingle CT (Johnson et al. Medicine 1985), case studiesTPE useful in rapid lowering of Anti-GBM AbLower post-treatment serum creatinine, decreased incidence of ESRDNEED ADJUNCT IMMUNOSUPPRESSIVE REGIMENFollow antibody levels for end point
4Rapidly Progressive GN (non Anti-GBM) RPGN- most patients have evidence of antibody associated disease (ANCA), or known immune complex disease - IgA, Cryoglobulinemia,lupusCase reports (favorable), CT-no favorable generalized benefit (Cole et al. 1992, AJKD) (when TPE added to standard immunosuppressive therapy)
5Rapidly 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)
6Multiple Myeloma with Renal Failure Cast Nephropathy resulting from light chain toxicityTPE in conjunction with proper anti neoplastic regimen improves on a more likely return of renal functionEvidence: CT (n=29) (Zucchelli et al. KI, 1988)- strong supportRecommend- 5 consecutive daily TPE treatments-early in course
7Multiple Myeloma with Renal Failure Caveats:Must rule out other causes of renal failure as these patients tend to be relatively illIf renal failure well established- results not as good- better before onset of oligoanuria (Johnson et al. Arch Intern med, 1990)
8IgA Nephropathy & Henoch Schonlein Purpura ~ 10% of IgA presents as RPGNTPE rationale--removal of circulating IgAEvidence No CTs, case reports Treatment +/- other immunosuppressive agentsRecommend:Useful in RPGN presentation (Coppo et al. Plasma Ther Transfus Technol, 1985)Likely minimal role in chronic disease
9HSP (Hattori et al, Am J Kid Dis, 1999, 33:427-33) 9 children with RPGN with HSP Rx with PP without immunosuppressionProteinuria ~ 4.9 gms/m2GFR ~ 46 mls/min/1.73 m26/9 complete recovery2/9 rebound with proteinuria with progression to ESRD
10CryoglobulinemiaRenal Manifestations- glomerular capillary deposition of cryoglobulin or immune complex disease with complement activation and vasculitisEvidence: No CTs, case reports and uncontrolled trialsConsensus: Useful adjunct in treatment of severe disease (progressive RF, coalescing purpura, advanced neuropathy) (D’Amico et al. KI, 1989)
11Cryoglobulinemia 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
12Hemolytic 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)
13Hemolytic Uremic Syndrome Evidence- limited-works in TTP? Why not HUS-adult outcome usually worseSUBGROUPS: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
14Systemic 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 diseaseRecommend: no evidence to support use
15Antiphospholipid Antibody Syndrome, Anticardiolipin Antibodies, Lupus anticoagulant Associated with venous & arterial thrombosis, fetal loss and occasional renal diseaseEvidence- no CTs, case reportsLimited 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
16SclerodermaScleroderma with ANCA positive patients, normal renin levels, normotensive associated renal diseaseEvidence: 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
17Focal Segmental Glomerulosclerosis Group: Recurrence Post-transplant (15-55% recurrence)- thought to be due to a circulating factor not yet specifically isolatedEvidence - strong no CTs, case reports with clinical and proteinuria improvement (Artero et al., AJKD, 1994)Recommend: Daily therapy (early) for up to 2 weeks
18Focal Segmental Glomerulosclerosis Group: Native FSGSMultiple etiologies, therefore need to evaluate carefullyEvidence: equivocal- may offer benefit in treatment resistant forms of primary FSGSRecommend: Clinically based
19Panel Reactive Antibody Reduction Transplant Candidates with high titers of cytotoxic antibodies- high rate of hyperacute rejection of transplanted graftsOther therapies also offered-ie monthly IVIG infusions-currently undergoing trialsEvidence: 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
20Acute 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
21Acute Hepatic Failure (Singer et al, Ann Surg, 2001 234:418-24) 49 children with FHF Rx with PP forHepatic support for recovery/bridge to TxCorrection of coagulationResults3/49 (8%) complete recovery32/49 (64%) bridge to Tx14/49 (28%) died due to FHFNo complications from PP
22PP with or without HF in Sepsis New generation of HF machines now have capability for PPCan be done simultaneously with HF with all current machineryDoes data exist in this area?
24HF + Plasma filtration adsorption 10 pts with SS10 hrs of PFA + CVVHD vs CVVHD aloneMAP > with PFA (p = 0.001)11.8 vs 5.5 mmHgNorepi < with PFA (P =0.003 )0.08 vs 0.005TNF alpha production > with PFA (p = 0.009)Ronco et al CCM :1387-8
25Plasma exchange and sepsis 76 adult pts with DIC/MOSF/ARF-66%Ventilated-72%Shock-88%Rx with PE until DIC reversedAvg 2 (range 1-14)Predicted mortality rate ~ 80% with Survival rate 82%(Stegmayr et al CCM :1730-6)
26Sepsis Rx with PE Tetta C et al Nguyen el al Ped CCM 2001 2:187-196 Nephrol Dial Transpl :Use of sorbent adsorption for cytokine removalNguyen el al Ped CCM :Rx with PE for Rx of microvascular thrombosis
27Sepsis Rx with PE Winchester et al Blood Purif 21:79-84 Tetta el al Use of target sorbentsTetta el alTher Apher 2002 :109-15Int Care Med :1222-8Artif Organs :202-13Sorbents, adsorption, PE
28Indication of TPE Category 1: Standard acceptable therapy Chronic idiopathic demyelinating polyneuropathy (CIDP), cryoglobulinemia, Goodpasture’s syndrome, Guillain-Barre syndrome, focal segmental glomerulonephritis, hyperviscosity, myasthenia gravis, post transfusion purpura, Refsum’s disease, TTP
29Indication of TPE Category 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
30Indication of TPE Category 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.
31Indication of TPE Category 4: Lack of efficacy in controlled trials. Examples: AIDS, amyotrophic lateral sclerosis, lupus nephritis, psoriasis, renal transplant rejection, schizophrenia, rheumatoid arthritis
32Risk Benefit ratiosDifficulty of basing all decision on patient care on controlled trial data (retrospective or prospective) is that one will not advance thought processIf the therapy has known and controlled risks and is safe then do not the potential benefits potentially out weigh the risks?