Kidney Transplant. November 4 th, 2016

Transcription

1 Kidney Transplant November 4 th, 2016 Brad West, MD, FACP Medical Director of Transplant Services, Memorial Medical Center Chairman Department of Nephrology, Springfield Clinic 1

2 Adjusted survival: incident patients Transplant has better outcomes than Dialysis Incident dialysis patients & patients receiving a first transplant in the calendar year. All probabilities are adjusted for age, gender, & race; overall probabilities are also adjusted for primary diagnosis. All ESRD patients, 1996, used as reference cohort. Modality determined on first ESRD service date; excludes patients transplanted or dying during the first 90 days. 2

3 Benefit of transplant versus waiting list? Wolfe et al, NEJM 1999;341:1725 Age Without Transplant With Transplant Difference y 39 y 13 y y 31y 17y y 22y 11y y 10y 4y 3

4 GFR distribution by year transplant Segev et al. JASN

5 KI 1.5 Characteristics of adult patients on the kidney transplant waiting list on December 31, 2002 & December 31,

6 Post Transplant Diabetes Risk Kuypers et al. Nephrol Dial Transplant

7 KI 6.11 Post-transplant diabetes among kidney transplant recipients by BMI 7

8 BMI at MMC 50 40% Diabetic BMI

9 Post Transplant Diabetes (PTDM) Risk factors for PTDM BPAR Steroid use Tacrolimus Family history Improved Kidneys BMI Age Result of PTDM Patient overall survival Kidney transplant survival 9 9

10 KI 4.1 Total kidney transplants Nationwide 10

11 KI 1.10 Three-year outcomes for adult patients waiting for a kidney transplant among new listings in

12 KI 1.1 Adult patients waiting for a kidney transplant 12

13 KI 3.1 living donors, by donor relation Living donors key to shortening wait times 13

14 KI 3.5 living kidney donor complications Low complication rates 14

15 KI 6.7 Half-lives for adult kidney transplant recipients..living Kidneys Work better! 15

16 Evaluation for Transplant EKG CXR Blood work ABO (blood type) Tissue Typing (HLA) Viral Serology Standard Cancer screening Colonoscopy Prostate Pap / Mammogram Other diagnostic testing (as needed) Cardiac Tests Urological tests Pulmonary Tests Frailty testing Vaccinations Pneumonia Influenza Shingles 16

17 Kidney Transplant Surgery The transplanted kidney is attached to the blood supply Artery Vein The ureter (urine draining tube) is attached to your bladder Surgery lasts about 3 4 hours 17

18 Brief Case 30 year old man on dialysis for 1 year got a transplant with IL2 induction He developed F fever on day 2, and urine decreased 6 hours later Preoperative immunological studies HLA 0/6 match PRA 6% (DR9) Flow Cross-match negative 18

19 KI 6.9 Incidence of first acute rejection among adult patients receiving a kidney transplant in

20 Transplant History 1950 Ruth Tucker -Little Company of Mary 1957 Azathioprine 1972 MMC, Dr. Birtch 1980s 50-60% Rejection 1983 CYCLOSPORINE 1986 OKT3 1990s 30% Rejection 1995 Mycophenolate 1994 Tacrolimus 1998 Hand Transplant, Lyon 2005 Face Transplant, Lyon 2000s <10-15% Rejection 2013 VCA Established at MMC Herrick Brothers (above) 1954 Dr Joseph Murray, Boston 20

21 Immunosuppressant Induction Thymoglobulin (Polyclonal) Cytokine release syndrome Administer through a high-flow vein. Pre-medication 1 hour prior corticosteroids Acetaminophen antihistamine (Benadryl) WBC count 2,000 to 3,000 cells/mm 3 or platelet count 50,000 to 75,000 cells/mm 3 : Reduce dose by 50%. WBC count <2,000 cells/mm 3 or platelet count <50,000 cells/mm 3 : Consider discontinuing treatment Basiliximab (IL2) 20 mg within 2 hours prior to transplant surgery, followed by a second 20 mg dose 4 days after transplantation 21

22 Maintenance Immunosuppression 1. Primary Immunosuppressant Tacrolimus Cyclosporine Sirolimus Belatacept (IV) 2. Anti-metabolite Mycophenolate Azathioprine 3. Prednisone 22 22

23 Calcineurin Inhibitor interactions Calcium channel blockers Proton Pump Inhibitors (less with Pantoprazole) Statins (less with Pravastatin) Antifungal therapies St. Johns Wort Conivaptan Protease inhibitors Decreased with cinacalcet, Dilantin QT prolonging drugs: Quinolones, Thioridazine 23

24 Side effects Cyclosporine Hirsutism, gingival hyperplasia, lipid abnormalities Tacrolimus side effects Diarrhea, Headache, Tremors, Hyperkalemia, ARF, Thrombotic microangiopathy (rare) Mycophenolate side effects Diarrhea, Leukopenia, Pancytopenia CMV Disease Diarrhea, Leukopenia, Pancytopenia Ebstein Barr Virus and BK Virus 24

25 Acute kidney failure- (Native Kidneys) Pre-renal Renal Post-renal Glomerular (<5%) Interstitial (<5%) Tubular (90%) Vasculitis (<5%) Obstructive Toxic Cast Nephropathy Acyclovir Oxalate Ischemic Aminoglycosides Myoglobin 25

26 Acute kidney failure- (Transplant) Pre-renal -RENAL VEIN/ARTERY Renal Post-renal URETER ANASTOMOSIS Glomerular (<5%) Interstitial Tubular Vasculitis Rejection vs BK Virus Calcineurin Oxalate Ivig ATN 26

27 Back to our patient.. 30 year old man developed F fever and kidney failure 2 days after transplantation

28 BIOPSY RESULTS 28

29 Our patient had a bad case of REJECTION! 29 29

30 Repeat Immunological studies New Donor Specific Antibody (DSA) detected DR7 B and T cell cross-match now positive as well Biopsy shows both BANFF 2 A Cellular Rejection Humoral rejection 30

31 Purpose of Banff Staging- Prognosis and Treatment Mueller et al Transplantation 2000 Mar 27;69(6):

32 Update On Patient Treated with Cellular Rejection; Thymoglobulin & steroids Humeral Rejection; IVIG & Rituximab Result: Home off and off dialysis 32

33 Patient home and doing well

34 THE TRANSPLANT TEAM 34 34

35 Questions? Transplant office: National Kidney Foundation (NKF) United Network for Organ Sharing (UNOS) American Society of Transplantation (AST) SRTR 35

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40 Humoral rejection (Antibody-mediated) Positive antibodies Histological Findings C4d Graft dysfunction Staging Type I - An acute tubular necrosis-like histology, with minimal inflammation Type II - A capillary-glomerulitis, with margination and/or thromboses Type III - Arterial-transmural inflammation/fibrinoid changes. 40

41 What is C4d? 41

42 C4d Physiology and Prognosis C4->C4a, C4b-> C4b is converted into C4d, C4d binds covalently to the endothelial and collagen basement membranes Why in the Peritubular capillary (PTC)? Glomerulus has 4 cell surface complement inhibitors» Decay accelerating factor (CD55)» membrane co-factor protein (CD46)» CR1 (complement receptor 1)-CD35» protectin (CD59 ) PTC has only one- Protectin (CD59) C4d relative risk (RR) of graft loss in 126 biopsies for Acute rejection RR 8.72 (CI 95% 2.24 to 19.03),» Herzenberg AM; Gill JS; Djurdjev O; Magil AB; C4d deposition in acute rejection: an independent long-term prognostic factor. J Am Soc Nephrol 2002 Jan;13(1):

43 Humoral Rejection Treatment Alemtuzumab and thymoglobulin Cellular rejection treatments Rituximab (CD20) Bortezomib (Tyrosine Kinase) IVIG & Plasmapheresis Eculizumab (C5) 43

44 Maintenance Immunosuppression Solumedrol 500 mg POD0 200 mg POD1 160 mg POD2 120 mg POD3 80 mg POD 4 40 mg POD 5 20 mg POD 6 Wean 5 mg q 2 weeks until at 5 mg daily. Mycophenolate Mofetil 1000 mg po BID, first dose pre-op Tacrolimus goal 8-11 first 3 months 5-8 thereafter 44

45 Infectious prophylaxis High risk Valgancyclovir 900 mg daily Moderate risk Valgancyclovir 450 mg daily Low risk Acyclovir 400 mg po BID Trimethoprim DS MWF Fungal prophylaxis Nystatin Fluconazole GI Prophylaxis Vitamin D supplementation 45

46 CHRONIC REJECTION Grade I Mild interstitial fibrosis 6-25% mild atrophy of the tubules (<25%) Grade II Moderate interstitial fibrosis 25-50% And moderate tubular atrophy 25-50%) Grade III Severe interstitial fibrosis >50% And tubular atrophy >50% Severity of glomerular, mesangial matrix, and vascular change is also quantified 46

47 CHRONIC ALLOGRAFT FAILURE FROM NEPHROPATHY Accounts for <4% of failures. DM - Primary focal segmental glomerulosclerosis relative contraindication to living donor transplant- >65% recur IgA 20% to 75% recur, but <10% graft loss. MPGN type % recurrence, 30-40% loss MPGN type % recurrence, 10-20% loss Anti GBM disease titers should be negative for 6 months before transplant. SLE/ANCA vasculitis avoid if active disease Fabry disease/hyperoxaluria Disease always recurs 47

48 Campath (Anti CD-52) Basu. Transplant Proc (Pittsburg) Alemtuzumab (anti-cd52) CD-52 on B and T-cells, monocytes, macrophages, and NK cells. Has ½ life of days 40 pt series in Steroid resistant rejection and Banff grade 1B or higher rejection on FK mono. 62.5% graft survival 4 patients had an infection» 2 died (PTLD, and infected hematoma) 48

49 CHRONIC REJECTION Grade I Mild interstitial fibrosis 6-25% mild atrophy of the tubules (<25%) Grade II Moderate interstitial fibrosis 25-50% And moderate tubular atrophy 25-50%) Grade III Severe interstitial fibrosis >50% And tubular atrophy >50% Severity of glomerular, mesangial matrix, and vascular change is also quantified 49

50 CHRONIC ALLOGRAFT NEPHROPATHY Accounts for <4% of failures. DM - Primary focal segmental glomerulosclerosis relative contraindication to living donor transplant- >65% recur IgA 20% to 75% recur, but <10% graft loss. MPGN type % recurrence, 30-40% loss MPGN type % recurrence, 10-20% loss Anti GBM disease titers should be negative for 6 months before transplant. SLE/ANCA vasculitis avoid if active disease Fabry disease/hyperoxaluria Disease always recurs 50

51 Early Allograft Algorithm 51

52 BK virus Onset 8 weeks to 5 years Median is about months.» Randhawa PS; Human polyoma virus-associated interstitial nephritis in the allograft kidney. Transplantation 1999 Jan 15;67(1):103-9.» Ramos E; Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol 2002 Aug;13(8): » Vasudev B; BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int 2005 Oct;68(4):

53 C4D prognosis C4d relative risk (RR) of graft loss in 126 biopsies for Acute rejection RR 8.72 (CI 95% 2.24 to 19.03),» Herzenberg AM; Gill JS; Djurdjev O; Magil AB; C4d deposition in acute rejection: an independent long-term prognostic factor. J Am Soc Nephrol 2002 Jan;13(1): renal biopsies done within 6 months 35% vs 67% graft survival 1 year post diagnosis.» Lederer SR; Kluth-Pepper B; Schneeberger H; Albert E; Land W; Feucht HE; Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts. Kidney Int 2001 Jan;59(1):

54 BIOPSY RESULTS 54

55 BIOPSY RESULTS 55

56 Organ Allocation - History First successful Kidney transplant Southeast Organ Procurement Foundation (SEOPF) is formed 1977 SEOPF implements first computerized Organ matching system, United Network for Organ Sharing SEOPF establishes kidney center for round the clock donor organ placement United Network for Organ Sharing separates from SEOPF National Organ Transplant Act (NOTA) Enacted UNOS receives initial federal contract to operate to Organ Procurement and Transplantation Network (OPTN) US Department of Health and Human Services (HHS) publishes Final Rule for the operation of the OPTN 56

57 Immunosuppressants NEJM 351;26,

58 NOTA- national Organ Transplant Act Prohibits Buying and Selling Organs Establishes two department of Health and Human Services (DHHS) Contracts: Organ Procurement and Transplantation Network (OPTN) Responsible for Organ Allocation policy development Responsible for Organ allocation Scientific Registry of Transplant Recipients (SRTR) Provides Ongoing Evaluation of the Scientific and Clinical Status of Organ Transplantation Data Collection 58

59 Public Health Service High Risk Behaviors indicating high risk donors Men who have had sex with another man within 5 years IV drug use within 5 years Men and women who have engaged in sex in exchange for money or drugs within 5 years Inmates of correctional systems If screening for infection is negative organs are offered. Voluntary, Change your mind at any time Expands the pool of donors available to you 59

60 Acute Cellular Rejection Detailed BANFF staging Borderline changes no intimal arteritis, mild tubulitis (1-4 mononuclear cells/tubular cross section) 10 to 25 % involvement of the interstitium. Type I Significant interstitial inflammation (>25 percent of parenchyma affected) and Type 1A - moderate tubulitis (>4 mononuclear cells/tubular section). Type IB- severe tubulitis (>10 mononuclear cells/tubular section) Type II Arteritis found in at least one arterial cross section. Type IIA-Mild to moderate arteritis Type IIB- Severe arteritis, which is associated with greater than 25 percent loss of the luminal area Type III Transmural arteritis, and/or arterial fibrinoid alterations, and necrosis of medial smooth muscle cells occurring in association with lymphocytic inflammation of the vessel. 60