Kidney Transplant Program Standard Operating Procedure Manual Policies and Procedures High-Risk Renal Transplant/Long-Term Management: Positive Crossmatch Kidney Transplant Guidelines (Adult/Pediatric) Content Applies To: Transplant Center Scope: Transplant Center Multidisciplinary Team Purpose: The Transplant Center has established a written protocol for positive crossmatch kidney transplants. Policy/Description: I. Positive Crossmatch Kidney Transplant Protocol A. Patient Selection 1. Patients without a living negative crossmatch donor 2. Living donor positive crossmatch (related or unrelated) 3. The term “crossmatch” refers to the present of high titer anti-HLA antibodies in the recipient that have donor specific activity or crossreactivity. B. Serologic evaluation 1. Single antigen bead measurement of anti-HLA antibodies 2. T and B cell flow cytometric crossmatch using standard protocol 3. AHG T cell crossmatch C. Desensitization with IVIG in patients with donor reactivity (NIH-CDC or FCXM) 1. 3-4 d before transplant give 1.5 gm/kg IVIG divide in 3 doses over 3 days (Pre-Tx coordinator to arrange) 2. If baseline AHG crossmatch was positive, repeat before starting and after completion of course of IVIG. 3. If post-IVIG the AHG crossmatch negative, proceed with transplant without plasmapheresis Content Information KIDNEY-POL: 0200021A/P.003 Release Date: June 5, 2012 Next Review Date: 04/01/2015 Revision Dates: 03/01/2010; 06/01/2012 Approval: Site(s): Comments: [Original Implementation Date: January 1, 2005] 1 Kidney Transplant Program Standard Operating Procedure Manual Policies and Procedures D. Pre-conditioning with Thymoglobulin (1.5 mg/kg) induction for five consecutive days prior to scheduled surgery E. AHG POSITIVE after 1.5 g/kg IVIG: 1. Transplant cannot proceed F. AHG NEGATIVE, B cell positive flow cross match with a shift >300: Removal of Anti-donor HLA antibodies 1. Plasmapheresis (PP) prior to transplant a. Pre-Tx coordinator to arrange (coordinate with Tissue Typing Lab) b. Number of PP/IVIG depends on titer of anti-HLA antibodies c. 1 plasma volume exchange, replace with 5% albumin d. Follow each PP with IVIG 100 mg/kg (may round to 10 grams) in PITC e. Last PP exchange on morning of transplant, must be at 7am f. Donor type specific fresh frozen plasma (4 units) given after last PP exchange to replenish coagulation factors g. Coordinate PP with dialysis to complete both early in the day h. Pre- and post PP measurement of AHG T-cell and T and B flow crossmatch prior to preconditioning and day of surgery i. Check CBC daily during PP j. To OR when AHG crossmatch is NEGATIVE and B cell flow cross match <300 G. Immunosuppressive regimen 1. Mycophenolate mofetil 600mg/m2 per dose PO BID start at first pheresis 2. Thymoglobulin (1.5 mg/kg) induction for 5 consecutive days prior to transplant and then as per standard protocol 3. Corticosteroid therapy as per standard TAC/MMF/Pred protocol 4. Start Tacrolimus when renal function established as per standard protocol Content Information KIDNEY-POL: 0200021A/P.003 Release Date: June 5, 2012 Next Review Date: 04/01/2015 Revision Dates: 03/01/2010; 06/01/2012 Approval: Site(s): Comments: [Original Implementation Date: January 1, 2005] 2 Kidney Transplant Program Standard Operating Procedure Manual Policies and Procedures H. Monitoring Post-Transplant 1. Use pediatric volume for blood tests to minimize anemia 2. Advice the tissue typing lab that patient is receiving Thymoglobulin post-transplant thus flow crossmatch and anti-HLA antibody levels can be measured without interference. 3. Protocol biopsy at time of renal perfusion intraoperatively, days 3, 7, and 90 post transplant. 4. Order biopsy studies for Light microscopy, C4d and frozen core in liquid nitrogen and electron microscopy. 5. Daily CBC with differential, lyte panel, Prograf. 6. If transfusion necessary, may use standard RBC transfusion. I. Renal allograft dysfunction 1. Urgent biopsy will be considered for rise in s Creatinine >15% or for fever >100.5 F, or evidence of intravascular hemolysis. a. All biopsies should include studies with Light, C4D in frozen core-process and electron microscopy. Biopsies results should be obtained on day of the biopsy. J. Humoral Rejection a. Initiate PP same day if signs of HR on biopsy. Set up pheresis to be early in the day b. Call Transfusion Medicine Resident on call (127-05160) to set up. c. Utilize 5% albumin as replacement fluid and follow with 100 mg/kg IVIG rounded to 10 grams. d. Initiate pulse methylprednisolone therapy as described by kidney acute allograft rejection e. Monitor anti-HLA antibodies by flow crossmatch and/or single antigen flow beads to determine the number of PP needed for treatment. K. Cellular Rejection- same as for ABO compatible kidney transplants L. AHG NEGATIVE, B cell positive flow cross match with a shift <300 1. Transplant can proceed without pre-transplant PP. a. Premed with Dexamethasone 0.5mg/kg (max 20mg), diphenhydramine 1-1.5mg/kg per dose, acetaminophen 10-15mg/kg/dose (max 625 mg) b. Protocol kidney biopsy on POD 0 and 3-4 c. Immunosuppression otherwise the same as standard TAC/MMF/Pred protocol d. Monitor anti-HLA antibody titers following transplant using both T and B cell flow Content Information KIDNEY-POL: 0200021A/P.003 Release Date: June 5, 2012 Next Review Date: 04/01/2015 Revision Dates: 03/01/2010; 06/01/2012 Approval: Site(s): Comments: [Original Implementation Date: January 1, 2005] 3 Kidney Transplant Program Standard Operating Procedure Manual Policies and Procedures crossmatch and single antigen flow beads on days 3, 7 and weekly for the first month. e. No PP unless humoral rejection detected References: Medicare Condition of Participation §482.94 Patient and Living Donor Management Note(s): Content Information KIDNEY-POL: 0200021A/P.003 Release Date: June 5, 2012 Next Review Date: 04/01/2015 Revision Dates: 03/01/2010; 06/01/2012 Approval: Site(s): Comments: [Original Implementation Date: January 1, 2005] 4