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Indications for Plasmapheresis Timothy E. Bunchman Pediatric Nephrology & Transplantation.

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Presentation on theme: "Indications for Plasmapheresis Timothy E. Bunchman Pediatric Nephrology & Transplantation."— Presentation transcript:

1 Indications for Plasmapheresis Timothy E. Bunchman Pediatric 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 Goodpasture’s 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 (n=29) (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, 33:427-33)  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) (D’Amico 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 234:418-24)  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  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 < with PFA (P =0.003 ) –0.08 vs 0.005  TNF alpha production > with PFA (p = 0.009) HF + Plasma filtration adsorption Ronco et al CCM 2002 30:1387-8

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 31:1730-6)

26 Sepsis Rx with PE  Tetta C et al –Nephrol Dial Transpl 1998 13:1458-64 –Use of sorbent adsorption for cytokine removal  Nguyen el al Ped CCM 2001 2:187- 196 –Rx with PE for Rx of microvascular thrombosis

27 Sepsis Rx with PE  Winchester et al Blood Purif 21:79-84 –Use of target sorbents  Tetta el al –Ther Apher 2002 :109-15 –Int Care Med 2003 29:1222-8 –Artif Organs 2003 27:202-13  Sorbents, adsorption, PE

28 Indication 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

29 Indication 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

30 Indication 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.

31 Indication of TPE Category 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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