Chronic Renal Allograft Dysfunction An unsolved problem
|
|
- Denis Ray
- 6 years ago
- Views:
Transcription
1 hronic Renal Allograft Dysfunction An unsolved problem Johan (Hans) W. de Fijter, D, PhD Professor of edicine and Nephrology Director of the Kidney and the Pancreas Transplant Program eiden niversity edical enter eiden, The Netherlands atalan Transplantation Society, Barcelona arch 18 th, 2015
2 Graft survival, % Kidney Transplantation ong-term outcomes remain poor and inadequate year 5 year 10 year 90,6 91,1 91,5 88,7 100 D DD-S DD-E ,3 72, ,5 62, ,7 48, , White Americans Hispanic Americans African Americans TS E NOS WA NOS HA NOS AA Gondos A, et al. Transplantation 2013;95: S OPTN / SRTR: Annual Report 2007
3 Graft oss Death with function dominated by ardiovascular Disease 75% No Graft oss Kidney Transplant Recipients n= % Graft Failure incl. PNF 10.5% Death with Graft Function 28.2% 15.2% 13.8% 11.6% ardiovascular Infections alignancies Other 31.2% nknown ean follow-up: 50.3 ± 32.6 months El-Zoghby Z, et al. Am J Transplant. 2009;9:
4 Hazard Ratio by egfr Decline 12-onth egfr Distribution (%) Robust association between GFR and V-mortality One-year egfr <50 m/min/1.73m 2 is associated with inferior outcome Relationship between egfr and graft failure over 10-years follow-up (ox proportional hazard adjusted for multiple covariates) 32.0 Hazard ratio (95% I) egfr distribution month egfr (m/min/1.73m 2 ) Kasiske B, et al. Am J Kidney Dis 2011;57:
5 GFR a robust risk factor for cardiovascular mortality Standardized ardiovascular Event Rate (GP mean follow-up 2.8 years) 45 <45 Go AS et al, N Eng J ed 2004, 351:
6 umulative incidence of chronic renal failure Non-Renal Solid Organ Transplant recipients High risk of renal failure 0,35 0,30 0,25 0,20 0,15 iver ung Heart 0,10 0,05 0, onths since transplantation No. at risk iver 36,849 28,495 24,041 19,508 15,724 12,564 9,844 7,345 5,292 3,614 2,261 ung 7,643 5,633 4,316 3,184 2,327 1,629 1, Heart 24,024 19,885 17,238 14,687 12,341 10,022 7,997 6,104 4,526 3,096 1,991 From: Ojo AO, et al. N Engl J ed. 2003;349:
7 egfr (ml/min) Early NI-reduction in iver Transplant recipients Impressive improvement in native renal function Evolution of Renal Fuction over time (On-Treatment population) Renal endpoints at 24-months (ITT population) P= TA-WD EVR + rta TA- egfr (m/min/1.73m 2 ) ,7 77,5 67, EVR+rTA (n=184) TA elimination (n=163) TA- (n=186) Reduced TA/EVR 10, Time post Tx, months Saliba F. Presented at the AASD, 2012; Boston TA elimination/evr 14, Δ egfr (%) Saliba F, et al. Am J Transplant. 2013;3:
8 BENEFIT: long-term extension study Belatacept vs. NI: Renal Function at 5 Years Rostaing et al., Am J Transplant 2013;13:
9 hronic Renal Allograft Dysfunction Immunosuppression: Too much or not enough? Disease recurrence BK nephropathy hronic Renal Allograft Dysfunction ate ABR ate cellular and/or humoral rejection Transplant glomerulitis/-opathy 4d deposition in peritubular capillaries NI-induced nephrotoxicity Hyalinosis of arterioles Focal glomerulosclerosis IF/TA odified from: Pascual, et al. N Engl J ed. 2002;346: and olvin RB. N Engl J ed. 2003; 349:
10 Graft survival, % Anti-HA Abs detected after transplantation Inferior long-term renal allograft outcome Kidney allograft survival according to HA-Abs status (N=1014) NDSA (n=209) No anti-ha antibodies (n=712) DSA (n=93) 83% 70% P<0.001 P< Time after HA antibody testing, years 5 49% achmann N, et al. Transplantation. 2009:
11 Antibody-ediated Rejection Represents a small but definite component of renal transplant failure 4.6% nknown 11.7% Acute rejection 2% ABR 16.3% edical 75% No Graft oss Kidney Transplant Recipients n= % Graft Failure incl. PNF 10.5% Death with Graft Function 30.7% IF/TA 36.6% Glomerular ~15% Recurrent Disease ~15% Transplant Glomerulopathy Evidence from Histology: hronic tissue injury (any 2 of below): - Arterial intimal fibrosis w/o elastosis - Duplication of the GB - ulti-laminated PT basement membrane - IF/TA Evidence from Tissue staining: Ab action/deposition (e.g. d4 in PT) Evidence from Serology: Anti-HA or other anti-donor antibody ean follow-up: 50.3 ± 32.6 months El-Zoghby Z, et al. Am J Transplant. 2009;9:
12 4d-staining for the diagnosis of ABR Neither completely specific nor sensitive enough 1,2 4d Banff classification Fluctuations in 4d-status in a DSA-positive patient in the first post-transplant year d = 2 (focal) 4d = 0 (negative) 4d = 1 (minimal) 4d = 3 (diffuse) 0 Transplantation Time after transplantation - Progression to TGP in DSA-positive patients with micro-vascular inflammation, but w/o 4d deposition 3 - High endothelial cell-specific gene expression leading to ABR in renal transplant biopsy samples with DSA but w/o 4d 4 - Positive 4d occurs with recurrent glomerular diseases (N; IX-GN) 4 1. olvin RB. J Am Soc Nephrol. 2007;18: ; 2. oupy A, et al. Nat Rev Nephrol. 2012;8:348 57; 3. oupy A, et al. Am J Transplant. 2011;11:56 65; 4. Sis B, et al. Am J Transplant. 2009;9:
13 De novo donor-specific HA-antibodies Evidence derived from Histology, 4d-staining and Serology icrovascular inflammation 4d-positive PT staining uminex-based assays also have limitations: - What is the association between dndsa and risk of ABR? - What is the DSA-threshold for the diagnosis DSA-positive? - Role of IgG isotypes and/or the ability to bind complement? oupy A, et al. Nat Rev Nephrol. 2012;8:348 57; engel, et al. Am J Transplant. 2012;12:
14 Probability of Graft Survival Donor-specific anti-ha Abs after transplantation omplement fixing or non-complement fixing antibodies Probability of Graft Survival onsecutive patients, population-based study (N=1016) 1 Allograft survival and DSA-status Allograft survival DSA+1q-status 1.0 DSA 1.0 DSA DSA+, 1q DSA DSA+, 1q P<0.001 by log-rank test 0.2 P<0.001 by log-rank test Years after Transplantation No. at Risk DSA DSA Years after Transplantation No. at Risk DSA DSA+/1q DSA+/1q The distribution of graft-injury phenotypes and rates of allograft survival were similar across all classes. Both class I and class II of donor-specific anti-ha antibodies after transplantation were harmful 2 1. oupy A, et al. N Engl J ed. 2013;369: ; 2. efaucheur, et al. N Engl J ed. 2014;370:85 86.
15 ean Banff score ean Banff score omplement-binding DSAs Association with Tissue damage/inflammation ean Banff score Percent of patients ean Banff score ean Banff score Graft histopathology (N=1016) according to HA-DSA status A icrovascular inflammation 4 P<0.001 B 4d graft deposition 80 P<0.001 Transplant glomerulopathy 0.6 P< P< P< P< DSA- DSA+/1q- DSA+/1q DSA- DSA+/1q- DSA+/1q+ DSA- DSA+/1q- DSA+/1q+ D Interstitial inflammation and tubulitis E Interstitial fibrosis and tubular atrophy F Arteriosclerosis 2.0 P< P= P= Data based on 1016 kidney-allograft biopsies performed in the first year after transplantation. (845 at 1-year and 171 during acute rejection in the first year). oupy A, et al. N Engl J ed. 2013;369: DSA- DSA+/1q- DSA+/1q+ DSA- DSA+/1q- DSA+/1q+ DSA- DSA+/1q- DSA+/1q+ 0.0
16 umulative survival Antibodies not binding complement Equally associated with inferior graft survival Graft survival in RTRs tested for anti-ha immunoglobulin subclasses (n=274; 2008) no-abs Non-complement omplement fixing fixing Antibodies Antibodies (p<0.001)* (p=0.002) * Antibodies at the last date of testing *log rank test vs. no-antibodies Arnold et al. Transplant Int 2014;27: Years after transplantation
17 linical Immunosuppression ong-term outcome after kidney transplantation Diabetes; Hypertension; Hyperlipidemia Inadequate Renal Allograft Function - Structural vascular changes (Hyalinosis; apillaritis; Glomerulitis) - Irreversible renal changes (Fibrosis; Transplant Glomerulopathy)
18 1: Reduced exposure to NIs in RTRs ower rejection rates do not translate in better long-term outcome parameters egfr (G in m/min) Regimen tested Standard-dose sa ( ng/m first 3 months & ng/m thereafter) n egfr (-G) m/min BPAR % 1-Yr GS % ± ow-dose sa ( ng/m) ± ow-dose TA (3 7 ng/m) ± ow-dose sirolimus ± Ekberg, et al. N Eng J ed. 2007;357: EITE SYPHONY omparable egfr results at 3-years SYPHONY trial: 12-month and 36-month egfr a Standard sa ow sa ow Tac SR Ekberg H et al. Am J Transpl 2009;9: Treatment group
19 ow acute rejection rate vs. excess BKV replication ommon in RTRs and associated with graft loss Viruria median 16 weeks Retrospective analysis of 34,937 RTRs (SRTR: ) Significant difference in overall graft survival at 3 years Probability Time post-transplant (weeks) BK-PVAN 1 10% 1,2 BKV viremia ~10 20% 2 Viremia median 23 weeks Nephropathy median 28 weeks Overall graft survival BKV treatment within 6 mo No treatment within 6 mo og-rank p<0.001 BKV viruria 30 50% Time post-transplant (months) BKV seropositive ~90% 2,3 1. Egli A et al. J Infect Dis 2009;199:837 46; 2. Hirsch HH et al. N Engl J ed 2002;347:488 96; 3. Nickeleit V et al. N Engl J ed 2000;342: ; 4. Schold JD et al. Transpl Int 2009;22:626 34
20 2: Prolonged Ni/S vs. New-onset Diabetes Dominant impact on patient survival beyond the first Year After the first year, a history of acute rejection had no effect on outcome. ole EH. et al. lin J Am Soc Nephrol. 2008;3:
21 Freedom from BPAR (%) Empiric dose reduction/drug withdrawal Ni- and/or S-elimination with mtoris Patient free of BPAR ZES trial Ni-elimination with EVR at 4.5 months Intention-to-treat population ONEPT trial Ni-elimination with SR at 3-months Intention-to-treat population % 9.7% 1, % 3.4% 0, ,50 Steroid withdrawal 25 0 Everolimus (n=154) sa (n=146) Days post-transplant 0,25 0,00 p log Rank = Days post-transplant SR group sa group Adapted from Budde K et al. ancet 2011;377: ebranchu Y, et al. Am J Transplant. 2011;11:
22 Survival 3: Risk for de novo DSA and ABR 1. Incompatibility for HA class-ii antigens edian 10-year graft survival for the 15% of patients with de novo DSA was 40% lower than those w/o DSA (59% vs 96%, P<0.0001) 1,0 0,9 0,8 0,7 0,6 0,5 0,4 0,3 de novo DSA de novo anti-ha antibodies No antibody Pre-transplant anti-ha Follow-up, years P < Independent predictors for de novo DSA formation: 1) HA-DR mismatch 2) Non-adherence (pediatric recipients) 3) History of rejection or protocol biopsy with SR between month 0-6 Wiebe, et al. Am J Transplant. 2012;12:
23 AR-free survival (%) ost dndsa are HA-DQ specific inkage disequilibrium between HA-DR and -DQ AR-free survival by DR & DQ matching DQ & DR mismatch and corresponding DSA 100 ismatch (n) Patients (n, %) orresponding DSAs (n, %) DR & DQ vs. other categories: P=0.01 DR 0-DR 146 (28.9) 0 1-DR 263 (52.1) 20 (7.6) 2-DR 96 (19.0) 9 (9.4) 0-DQ 184 (36.4) 0 70 DQ 1-DQ 250 (49.5) 35 (14.0) 2-DQ 71 (14.1) 15 (21.1) DR/DQ zero [98.0%] DQ alone [97.4%] DR alone [98.6%] DR & DQ [88.5%] DR =0 DQ (21.4) 0 DQ 1 38 (7.5) 2 (5.3) DR 1 DQ 0 75 (14.9) 2 (2.7) DQ (56.2) 60 (21.1) Time post transplant (months) Willicombe, et al. Transplantation. 2012;94:
24 Risk for Antibody-mediated Rejection 2. Non-adherence For-cause biopsies (n=315) between with documented failure (n=56) in 3 N-A enters Polyoma virus nephropathy 7% edical/surgical conditions 11% 64% ABR, probably ABR or ixed rejection Glomerulonephritis 18% ABR 50% Probably ABR 9% ixed rejection 5% Sellares J, et al. Am J Transplant. 2012;12:
25 DSA occur with all types of immunosuppressive regimen 3. Inadequate Overall Immunosuppression Immunosuppression N DSA posttransplantation sa 43% (n=129)*; Tac 35% (n=106)* w/aza 16% (n=50)*; w/f 34% (n=102)* % (n=302): de novo HA antibodies 9.2% (n= 93): de novo DSA achmann N, et al. Transplantation 2009; 87: NI (sa or Tac) Prednisone F F (2 g/d); Prednisone Tac (8 10 ng/m: first 3 mo; 6 8 thereafter sa (2: ng/m first 3 mo; thereafter % (n=54) de novo DSA % (n=34) de novo DQ-DSA - 9,8% (n=20) de novo DQ-DSA + other DSA % (n=316) de novo DSA at 4.8 yrs. (0.2-7) 7.6% (n= 77) 1q+ Freitas A, et al. Transplantation. 2013;95: ; oupy A, et al. N Engl J ed. 2013;369: ; sa (n=129); Tac (n=57) % (n=47) de novo DSA within 10 years Everly J, et al. Transplantation. 2013;95: F/PA + sa + Pred F/PA + Tac + Pred Aza + sa + Pred sa/tac + Sir + Pred 78 16% de novo DSA within first year 19% de novo DSA within first year 5% de novo DSA within first year 3% de novo DSA within first year Banasik, et al. Transplant Proc. 2013;45: ; sa/tac F/ZR/AZA/EVR Tac+F+glucocorticoids: (n=48) sa+f+glucocorticoids: (n=4) EVR+sA+glucocorticoids: (n=3) % (n=39) de novo HA antibody Ashimine S, et al. Kidney Int. 2014;85:425 30; 55 10% de novo DSA at 1 year 28% de novo DSA at 3 years ibri I, et al. Am J Transplant. 2013;13: Belatacept, more intensive + F (n=219) 66 6% de novo DSA by year 3 Belatacept, less intensive + F (n=226) 5% de novo DSA by year 3 sa + F (n=221) oupy A et al. N Engl J ed 2013;369: % de novo DSA by year 3 *Data reflects proportion and numbers of patients with HA antibodies post-transplantation. Vincenti F, et al. Am J Transplant. 2012;12:
26 Inadequate control over immune reactivity Ni-elimination (mo 4.5) followed by Steroid-withdrawal in 60% Retrospective single-center analysis, pooled data from participation in two (comparable) trials Incidence of DSA (uminex) Incidence of late ABR (For-cause biopsy) Everolimus (14/61) p=0.048 Everolimus (8/61) iclosporine (7/65) p=0.036 iclosporine (2/65) DSA <d14 (n=2) Independent risk factors: Everolimus (=Ni/S stop) arm 2.67 ( ) iving donor 2.39 ( ) HA-mismatch ( ) iefeldt, et al. Am J Transplant. 2012;12: Independent risk factors: Everolimus (=Ni/S stop) arm 5.35 ( ) iving donor 5.78 ( ) HA-mismatch ( ) Treated AR first year ( )
27 4: Transplant Glomerulopathy Antibodies against non-ha antigens Transplant Glomerulopathy Gloor et al., Am J Transpl, 2007;7:2124
28 HA-identical Kidney Transplant Recipients (siblings) Impact of pre-transplant %-PRA (HA & non-ha antigens) 1-yr Graft survival according to PRA 10-yr Functional graft survival according to PRA Opelz et al., ancet 2005, 365:1570-6
29 Agonistic antibodies against the AT1-R Refractory vascular rejection in RTRs (n=33) Dragun D et al N Eng J ed 2005
30 Pretransplant H class I related chain A antibodies Early kidney graft loss and Tissue expression Pre-transplant antibodies against IA non HA-sensitized RTRs Sequential kidney biopsies pre-implantation and at day-7 stained with IB antibody (A) Very low levels of tubular IB expression on the renal tubules in the donor kidney biopsy (B) p-regulated IB expression 7 days post-transplant in proximal and distal tubular cytoplasm p=0.004 First graft/well matched/low-risk/non-sensitized Zou Y et al. N Engl J ed 2007;357: Quiroga I et al. Transplantation 2006;81:
31 hronic Renal Allograft Dysfunction Inadequate renal (allograft) function is a robust independent risk factor for excess cardiovascular mortality, especially with concomitant diabetes. ABR is a relative small component of overall graft loss 1, but a definite cause of premature graft failure 2 De novo DSA have been documented in RTRs while treated according to all major immunosuppressive maintenance regimen 7,8. ajor risk factors include Incompatibility for HA-class II, and/or Non-adherence, and/or Inadequate overall immunosuppression linical immunosuppression is further challenged by: ow acute rejection rates vs. excess BKV-replication Prolonged Ni- and S-use vs. unfavourable V risk profile (GFR/D/HT) Inappropriate (empiric) dose reduction(s) and chronic/late (humoral) rejection 1. El-Zoghby Z, et al. Am J Transplant. 2009;9: Sellares J, et al. Am J Transplant. 2012;12: Djamali A, et al. Am J Transplant 2014;14:255-71; 4. oupy A, et al. Nat Rev Nephrol. 2012;8:348 57; 5. Freitas, et al. Transplantation 2013;95: ; 6. oupy A, et al. N Engl J ed. 2013;369: ; 7. Vincenti F, et al. Am J Transplant ;12:210-7; 8. Ashimine S, et al. Kidney Int. 2013
Recognition and Treatment of Chronic Allograft Dysfunction
Recognition and Treatment of Chronic Allograft Dysfunction Alexander Wiseman, M.D. Associate Professor, Division of Renal Diseases and Hypertension Medical Director, Kidney and Pancreas Transplant Programs
More informationManagement of Rejection
Management of Rejection I have no disclosures Disclosures (relevant or otherwise) Deborah B Adey, MD Professor of Medicine University of California, San Francisco Kidney and Pancreas Transplant Center
More informationRisk Factors in Long Term Immunosuppressive Use and Advagraf. Daniel Serón Nephrology department Hospital Universitari Vall d Hebron
Risk Factors in Long Term Immunosuppressive Use and Advagraf Daniel Serón Nephrology department Hospital Universitari Vall d Hebron Progressive well defined diseases ABMR GN Polyoma Non-specific Findings
More informationDiagnosis and Management of Acute and Chronic Humoral Rejection. Lars Pape
Diagnosis and Management of Acute and Chronic Humoral Rejection Lars Pape Immunosuppression Acute rejection Chronic rejection Side effects Infections Nephrotoxicity Adult population Nearly all late rejection-related
More informationReview of Rituximab and renal transplantation. Dr.E Nemati. Professor of Nephrology
Review of Rituximab and renal transplantation Dr.E Nemati Professor of Nephrology Introductio n Rituximab is a chimeric anti-cd20 monoclonal antibody. The CD20 antigen is a transmembrane nonglycosylated
More informationHLA and Non-HLA Antibodies in Transplantation and their Management
HLA and Non-HLA Antibodies in Transplantation and their Management Luca Dello Strologo October 29 th, 2016 Hystory I 1960 donor specific antibodies (DSA): first suggestion for a possible role in deteriorating
More informationJames E. Cooper, M.D. Assistant Professor, University of Colorado at Denver Division of Renal Disease and Hypertension, Kidney and PancreasTransplant
James E. Cooper, M.D. Assistant Professor, University of Colorado at Denver Division of Renal Disease and Hypertension, Kidney and PancreasTransplant Program Has no real or apparent conflicts of interest
More informationStatement of Disclosure
Statement of Disclosure Mark Haas serves as a paid consultant on pathology adjudication committees for two industry-sponsored clinical trials: Shire ViroPharma Treatment of Acute ABMR AstraZeneca Treatment
More informationThe new Banff vision of the role of HLA antibodies in organ transplantation: Improving diagnostic system and design of clinical trials
The new Banff vision of the role of HLA antibodies in organ transplantation: Improving diagnostic system and design of clinical trials Carmen Lefaucheur 1 2 Banff 2015: Integration of HLA-Ab for improving
More informationBiopsy Features of Kidney Allograft Rejection Banff B. Ivanyi, MD Department of Pathology, University of Szeged, Szeged, Hungary
Biopsy Features of Kidney Allograft Rejection Banff 2017 B. Ivanyi, MD Department of Pathology, University of Szeged, Szeged, Hungary Treatment of allograft dysfunction should rely on the biopsy findings
More informationLiterature Review Transplantation
Literature Review 2010- Transplantation Alexander Wiseman, M.D. Associate Professor, Division of Renal Diseases and Hypertension Medical Director, Kidney and Pancreas Transplant Programs University of
More informationThe Banff Classification for Diagnosis of Renal Allograft Rejection: Updates from the 2017 Banff Conference
The Banff Classification for Diagnosis of Renal Allograft Rejection: Updates from the 2017 Banff Conference Mark Haas Cedars-Sinai Medical Center Los Angeles, California, USA Statement of Disclosure Mark
More informationSELECTED ABSTRACTS. All (n) % 3-year GS 88% 82% 86% 85% 88% 80% % 3-year DC-GS 95% 87% 94% 89% 96% 80%
SELECTED ABSTRACTS The following are summaries of selected posters presented at the American Transplant Congress on May 5 9, 2007, in San Humar A, Gillingham KJ, Payne WD, et al. Review of >1000 kidney
More informationPathological back-ground of renal transplant pathology and important mile-stones of the Banff classification
Banff 1 Banff Pathological back-ground of renal transplant pathology and important mile-stones of the Banff classification Department of Nephrology, Japanese Red Cross Nagoya Daini Hospital Morozumi Kunio,
More informationCase Presentation Turki Al-Hussain, MD
Case Presentation Turki Al-Hussain, MD Director, Renal Pathology Chapter Saudi Society of Nephrology & Transplantation Consultant Nephropathologist & Urological Pathologist Department of Pathology & Laboratory
More informationCKD in Other Organ Transplants
CKD in Other Organ Transplants Alexander Wiseman, M.D. Associate Professor, Division of Renal Diseases and Hypertension Medical Director, Kidney and Pancreas Transplant Programs University of Colorado
More informationSteroid Minimization: Great Idea or Silly Move?
Steroid Minimization: Great Idea or Silly Move? Disclosures I have financial relationship(s) within the last 12 months relevant to my presentation with: Astellas Grants ** Bristol Myers Squibb Grants,
More informationImmunopathology of T cell mediated rejection
Immunopathology of T cell mediated rejection Ibrahim Batal MD Columbia University College of Physicians & Surgeons New York, NY, USA Overview Pathophysiology and grading of TCMR TCMR is still a significant
More informationRENAL EVENING SPECIALTY CONFERENCE
RENAL EVENING SPECIALTY CONFERENCE Harsharan K. Singh, MD The University of North Carolina at Chapel Hill Disclosure of Relevant Financial Relationships No conflicts of interest to disclose. CLINICAL HISTORY
More informationBK virus infection in renal transplant recipients: single centre experience. Dr Wong Lok Yan Ivy
BK virus infection in renal transplant recipients: single centre experience Dr Wong Lok Yan Ivy Background BK virus nephropathy (BKVN) has emerged as an important cause of renal graft dysfunction in recent
More informationDSA Positive and then To biopsy or not?
DSA Positive and then To biopsy or not? Banff SCT 2017 29 March 2017 Peter Nickerson, MD, FRCPC, FCAHS Flynn Family Chair in Renal Transplantation Professor of Internal Medicine and Immunology Relevant
More informationUpdate on Transplant Glomerulopathy
Update on Transplant Glomerulopathy Miklos Z Molnar, MD, PhD, FEBTM, FERA, FASN Associate Professor of Medicine Division of Nephrology, Department of Medicine University of Tennessee Health Science Center
More informationKidney Summary. Mark Haas Cedars-Sinai Medical Center Los Angeles, California, USA
Kidney Summary Mark Haas Cedars-Sinai Medical Center Los Angeles, California, USA Key Issues to Address re: the Classification 1. Incorporation of i-ifta + tubulitis into the TCMR classification - Defining
More informationLong-term prognosis of BK virus-associated nephropathy in kidney transplant recipients
Original Article Kidney Res Clin Pract 37:167-173, 2018(2) pissn: 2211-9132 eissn: 2211-9140 https://doi.org/10.23876/j.krcp.2018.37.2.167 KIDNEY RESEARCH AND CLINICAL PRACTICE Long-term prognosis of BK
More informationRenal Pathology- Transplantation. Eva Honsova Institute for Clinical and Experimental Medicine Prague, Czech Republic
Renal Pathology- Transplantation Eva Honsova Institute for Clinical and Experimental Medicine Prague, Czech Republic eva.honsova@ikem.cz Kidney has a limited number of tissue reactions by which the kidney
More informationChronic Calcineurin Inhibitor Nephrotoxicity: Myth or Reality?
Chronic Calcineurin Inhibitor Nephrotoxicity: Myth or Reality? Aji Djamali, MD Associate Professor of Medicine and Surgery Division Chief Nephrology University of Wisconsin School of Medicine and Public
More informationPathology of Kidney Allograft Dysfunction. B. Ivanyi, MD Department of Pathology, University of Szeged, Szeged, Hungary
Pathology of Kidney Allograft Dysfunction B. Ivanyi, MD Department of Pathology, University of Szeged, Szeged, Hungary The gold standard for exploration of the cause of an allograft dysfunction is to perform
More informationPost-Transplant Monitoring for the Development of Anti-Donor HLA Antibodies
Post-Transplant Monitoring for the Development of Anti-Donor HLA Antibodies Lorita M Rebellato, Ph.D., D (ABHI) Associate Professor Department of Pathology The Brody School of Medicine at ECU Scientific
More informationLiterature Review: Transplantation July 2010-June 2011
Literature Review: Transplantation July 2010-June 2011 James Cooper, MD Assistant Professor, Kidney and Pancreas Transplant Program, Renal Division, UC Denver Kidney Transplant Top 10 List: July Kidney
More informationCase Report Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration Rate
Case Reports in Transplantation, Article ID 190516, 4 pages http://dx.doi.org/10.1155/2014/190516 Case Report Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration
More informationDr Ian Roberts Oxford
Dr Ian Roberts Oxford Oxford Pathology Course 2010 for FRCPath Present the basic diagnostic features of the commonest conditions causing renal failure Highlight diagnostic pitfalls. Crescentic GN: renal
More informationIntruduction PSI MODE OF ACTION AND PHARMACOKINETICS
Multidisciplinary Insights on Clinical Guidance for the Use of Proliferation Signal Inhibitors in Heart Transplantation Andreas Zuckermann, MD et al. Department of Cardio-Thoracic Surgery, Medical University
More informationRecurrent Idiopathic Membranous Glomerulonephritis After Kidney Transplantation and Successful Treatment With Rituximab
TRANSPLANTATION Recurrent Idiopathic Membranous Glomerulonephritis After Kidney Transplantation and Successful Treatment With Rituximab Khadijeh Makhdoomi, 1,2 Saeed Abkhiz, 1,2 Farahnaz Noroozinia, 1,3
More information2017 BANFF-SCT Joint Scientific Meeting. BARCELONA March 2017
2017 BANFF-SCT Joint Scientific Meeting BARCELONA 27-31 March 2017 Adriana Zeevi PhD (D) ABHI Professor of Pathology, Surgery and Immunology Director of Histocompatibility Laboratory University of Pittsburgh
More informationKidneytransplant pathologyrelatedto immunosuppressiveagents
Kidneytransplant pathologyrelatedto immunosuppressiveagents Helmut Hopfer Pathologie Women, 53 years old. 16 months after kidney transplantation for diabetic nephropathy. Metabolicsyndromeandcoronaryheartdisease.
More informationWhy Do We Need New Immunosuppressive Agents
Why Do We Need New Immunosuppressive Agents 1 Reducing acute rejection rates has not transplanted into better long-term graft survival Incidence of early acute rejection episodes by era Relative risk for
More informationPREVENTION AND TREATMENT OF BKV NEPHROPATHY Petra Reinke, Berlin, Germany. Chair: Daniel Abramowicz, Brussels, Belgium Rosanna Coppo, Turin, Italy
PREVENTION AND TREATMENT OF BKV NEPHROPATHY Petra Reinke, Berlin, Germany Chair: Daniel Abramowicz, Brussels, Belgium Rosanna Coppo, Turin, Italy Prof Petra Reinke Department of Nephrology University Hospital
More informationThe Histology of Kidney Transplant Failure: A Long-Term Follow-Up Study
CLINICAL AND TRANSLATIONAL RESEARCH The Histology of Kidney Transplant Failure: A Long-Term Follow-Up Study Maarten Naesens, 1,2,6 Dirk R.J. Kuypers, 1,2 Katrien De Vusser, 1,2 Pieter Evenepoel, 1,2 Kathleen
More informationCurrent Trends in Kidney Transplantation: The Role of Nonadherence
Current Trends in Kidney Transplantation: The Role of Nonadherence Donald E. Hricik, MD Professor of Medicine Case Western Reserve University Chief of the Division of Nephrology and Hypertension Medical
More informationPeritubular capillaries C4d deposits in renal allograft biopsies and anti HLA I/II alloantibodies screening Incidence and clinical importance
ORIGINAL ARTICLE Port J Nephrol Hypert 2008; 22(1): 37-42 Peritubular capillaries C4d deposits in renal allograft biopsies and anti HLA I/II alloantibodies screening Incidence and clinical importance Helena
More informationKidney transplantation 2016: current status and potential challenges
Kidney transplantation 2016: current status and potential challenges 15/12/2016 BVN-SBN : State-of-the-Art on Kidney Transplantation Patrick Peeters Ghent University Hospital, Belgium Challenges in 2016
More informationControversies in Renal Transplantation. The Controversial Questions. Patrick M. Klem, PharmD, BCPS University of Colorado Hospital
Controversies in Renal Transplantation Patrick M. Klem, PharmD, BCPS University of Colorado Hospital The Controversial Questions Are newer immunosuppressants improving patient outcomes? Are corticosteroids
More informationPosttransplant Human Leukocyte Antigen Antibodies in Stable Kidney Transplant Recipients
Trends in Transplant. 2014;8:3-9 Gregor Bartel, Georg A. Böhmig: Alloantibodies and Graft Function Posttransplant Human Leukocyte Antigen Antibodies in Stable Kidney Transplant Recipients Gregor Bartel
More informationRECURRENT AND DE NOVO RENAL DISEASES IN THE ALLOGRAFT. J. H. Helderman,MD,FACP,FAST
RECURRENT AND DE NOVO RENAL DISEASES IN THE ALLOGRAFT J. H. Helderman,MD,FACP,FAST Vanderbilt University Medical Center Professor of Medicine, Pathology and Immunology Medical Director, Vanderbilt Transplant
More informationUpdate on Transplant Glomerulopathy
Update on Transplant Glomerulopathy Miklos Z Molnar, MD, PhD, FEBTM, FERA, FASN Associate Professor of Medicine Methodist University Hospital, Transplant Institute Division of Transplantation, Department
More informationProgress in Pediatric Kidney Transplantation
Send Orders for Reprints to reprints@benthamscience.net The Open Urology & Nephrology Journal, 214, 7, (Suppl 2: M2) 115-122 115 Progress in Pediatric Kidney Transplantation Jodi M. Smith *,1 and Vikas
More informationCase # 2 3/27/2017. Disclosure of Relevant Financial Relationships. Clinical history. Clinical history. Laboratory findings
Case # 2 Christopher Larsen, MD Arkana Laboratories Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee) in a position to influence or control the content
More informationVictims of success: Do we still need clinical trials? Robert S. Gaston, MD CTI Clinical Trials and Consulting University of Alabama at Birmingham
Victims of success: Do we still need clinical trials? Robert S. Gaston, MD CTI Clinical Trials and Consulting University of Alabama at Birmingham Disclosure Employee: CTI Clinical Trials and Consulting
More informationSupplementary appendix
Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Lefaucheur C, Loupy A, Vernerey D, et al. Antibody-mediated
More informationClinical Grand Rounds. May 2016
Clinical Grand Rounds May 2016 The Case 51M African American w/ HTN, ESRD (on HD for 13 years) who underwent a DDRTx in June 2015. Complications: BK viremia with AKI in Jan 2016---MMF held and tacro dose
More informationRisk factors in the progression of BK virus-associated nephropathy in renal transplant recipients
ORIGINAL ARTICLE Korean J Intern Med 15;3:865-872 http://dx.doi.org/1.394/kjim.15.3.6.865 Risk factors in the progression of BK virus-associated nephropathy in renal transplant recipients Hae Min Lee 1,*,
More informationAntibody Mediated Rejection (AMR) in LUNG TRANSPLANT Recipients
Antibody Mediated Rejection (AMR) in LUNG TRANSPLANT Recipients Lorriana Leard, MD UCSF Transplant Pulmonologist Associate Professor of Clinical Medicine Vice Chief of Clinical Activities Pulmonary, Critical
More informationPathology and Management of Chronic Allograft Dysfunction. Simin Goral, MD University of Pennsylvania Medical Center Philadelphia, Pennsylvania
Pathology and Management of Chronic Allograft Dysfunction Simin Goral, MD University of Pennsylvania Medical Center Philadelphia, Pennsylvania Mission Impossible? PLAN To review the description of chronic
More informationDonor-Specific HLA Antibodies in a Cohort Comparing Everolimus With Cyclosporine After Kidney Transplantation
American Journal of Transplantation 2012; 12: 1192 1198 Wiley Periodicals Inc. C Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/j.1600-6143.2011.03961.x
More informationDonor-derived Cell-free DNA Improves DSA-informed Diagnosis of ABMR in Kidney Transplant Patients
Donor-derived Cell-free DNA Improves DSA-informed Diagnosis of ABMR in Kidney Transplant Patients Stanley C. Jordan, MD Director, Division of Nephrology Medical Director, Kidney Transplant Program Medical
More informationPredictors of cardiac allograft vasculopathy in pediatric heart transplant recipients
Pediatr Transplantation 2013: 17: 436 440 2013 John Wiley & Sons A/S. Pediatric Transplantation DOI: 10.1111/petr.12095 Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients
More informationInterstitial Inflammation
Interstitial Inflammation Currently considered to be T cell-mediated process Plasma cell rich acute rejection often associated with AMR Preliminary data suggests that interstitial follicular helper T cells
More informationLe migliori strategie immunosoppressive per il paziente con re-trapianto Prof. Maurizio Salvadori FIRENZE
Le migliori strategie immunosoppressive per il paziente con re-trapianto Prof. Maurizio Salvadori FIRENZE Best Therapy for Kidney Re- Transplantation? PREVENTION!!!! Registries CTS OPTN UNOS USRDS SRTR
More informationNo evidence of C4d association with AMR However, C3d and AMR correlated well
C4d positivity Poor prognostic factor Reversal to C4d negativity did not change prognosis, with current therapy Prognostic factor for CAV Variable time line for CAV/death No correlation with cellular rejection
More informationImpact of Subclinical Rejection on Transplantation
Trends in Transplantation 2007;1:56-60 Impact of Subclinical Rejection on Transplantation David N. Rush for the Winnipeg Transplant Group Transplant Manitoba Adult Kidney Program, University of Manitoba,
More informationTolerance Induction in Transplantation
Tolerance Induction in Transplantation Reza F. Saidi, MD, FACS, FICS Assistant Professor of Surgery Division of Organ Transplantation Department of Surgery University of Massachusetts Medical School Percent
More informationKidney Allograft Fibrosis and Atrophy Early After Living Donor Transplantation
American Journal of Transplantation 2005; 5: 1130 1136 Blackwell Munksgaard Copyright C Blackwell Munksgaard 2005 doi: 10.1111/j.1600-6143.2005.00811.x Kidney Allograft Fibrosis and Atrophy Early After
More informationKidney Transplant. November 4 th, 2016
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 Adjusted survival: 1993-1997
More information2017 CST-Astellas Canadian Transplant Fellows Symposium. Management of Renal Dysfunction in Extra Renal Transplants
2017 CST-Astellas Canadian Transplant Fellows Symposium Management of Renal Dysfunction in Extra Renal Transplants Jeffrey Schiff, MD Dr. Jeffrey Schiff is an Assistant Professor of Medicine at the University
More informationChronic Kidney Disease (CKD) Stages. CHRONIC KIDNEY DISEASE Treatment Options. Incident counts & adjusted rates, by primary diagnosis Figure 2.
Chronic Kidney Disease (CKD) Stages Stage 1 GFR > 90 (evidence of renal disease) Stage 2 GFR 60-89 Stage 3 GFR 30-59 Stage 4 GFR 15-29 Stage 5 GFR
More informationUtility of protocol kidney biopsies for de novo donor- specific antibodies
Received: 6 June 2017 Revised: 24 July 2017 Accepted: 29 July 2017 DOI: 10.1111/ajt.14466 BRIEF COMMUNICATION Utility of protocol kidney biopsies for de novo donor- specific antibodies Sandesh Parajuli
More informationHLA Part II: My Patient Has DSA, Now What?
2017 CST-Astellas Canadian Transplant Fellows Symposium HLA Part II: My Patient Has DSA, Now What? James Lan, MD, FRCPC, D(ABHI) Dr. Lan completed his nephrology training at the University of British Columbia.
More informationPathology of Kidney Allograft Dysfunction. B. Ivanyi, MD Department of Pathology, University of Szeged, Szeged, Hungary
Pathology of Kidney Allograft Dysfunction B. Ivanyi, MD Department of Pathology, University of Szeged, Szeged, Hungary The renal biopsy is a powerful tool in the diagnostic evaluation of allograft dysfunction
More informationThe New Kidney Allocation System: What You Need to Know. Anup Patel, MD Clinical Director Renal and Pancreas Transplant Division Barnabas Health
The New Kidney Allocation System: What You Need to Know Anup Patel, MD Clinical Director Renal and Pancreas Transplant Division Barnabas Health ~6% of patients die each year on the deceased donor waiting
More informationCases: CMV, HCV, BKV and Kidney Transplantation. Simin Goral, MD University of Pennsylvania Medical Center
Cases: CMV, HCV, BKV and Kidney Transplantation Simin Goral, MD University of Pennsylvania Medical Center Disclosures Grant support: Otsuka Pharmaceuticals, Astellas Pharma, Angion, AstraZeneca, and Kadmon
More informationIntravenous immunoglobulin in BK virus nephropathy
Washington University School of Medicine Digital Commons@Becker Open Access Publications 2014 Intravenous immunoglobulin in BK virus nephropathy Elizabeth I. Anyaegbu Driscoll Children's Hospital Stanley
More informationAntibody-Mediated Rejection in the Lung Allograft. Gerald J Berry, MD Dept of Pathology Stanford University Stanford, CA 94305
Antibody-Mediated Rejection in the Lung Allograft Gerald J Berry, MD Dept of Pathology Stanford University Stanford, CA 94305 Gerald J Berry, MD Professor of Pathology Stanford University, Stanford, CA
More informationRECURRENT AND DE NOVO RENAL DISEASES IN THE ALLOGRAFT
RECURRENT AND DE NOVO RENAL DISEASES IN THE ALLOGRAFT HISTOPATHOLOGIC DISORDERS AFFECTING THE ALLOGRAFT OTHER THAN REJECTION RECURRENT DISEASE DE NOVO DISEASE TRANSPLANT GLOMERULOPATHY Glomerular Non-glomerular
More informationTransfusion support in Transplantation
Transfusion support in Transplantation Patricia Campbell University of Alberta Hospitals University of Alberta Objectives UofA transplant programs What we do and why? HLA and ABO incompatible transplants
More informationChronic renal histological changes at implantation and subsequent deceased donor kidney transplant outcomes: a single-centre analysis
Chronic renal histological changes at implantation and subsequent deceased donor kidney transplant outcomes: a single-centre analysis Benedict Phillips 1, Kerem Atalar 1, Hannah Wilkinson 1, Nicos Kessaris
More informationInnovation In Transplantation:
Innovation In Transplantation: Improving outcomes Thomas C. Pearson Department of Surgery Emory Transplant Center CHOA Symposium October 22, 2016 Disclosures Belatacept preclinical and clinical trial were
More informationHistopathological evaluation of renal allograft biopsies in Nepal: interpretation and significance
Nepal Medical Association Building Exhibition Road, Kathmandu Journal of Pathology of Nepal (2012) Vol. 2, 172-179 Association of Clinical Pathologist of Nepal-2010 Journal of PATHOLOGY of Nepal www.acpnepal.com
More informationBK virus, kidney transplant, polycystic kidney disease. 1-3 Following mild or asymptomatic primary infection, typically early
Received: 22 June 2018 Revised: 17 July 2018 Accepted: 6 August 2018 DOI: 10.1111/tid.12974 ORIGINAL ARTICLE Kidney transplant recipients with polycystic kidney disease have a lower risk of post- transplant
More informationHasan Fattah 3/19/2013
Hasan Fattah 3/19/2013 AASK trial Rational: HTN is a leading cause of (ESRD) in the US, with no known treatment to prevent progressive declines leading to ESRD. Objective: To compare the effects of 2 levels
More informationMicrocirculation Inflammation Associates With Outcome in Renal Transplant Patients With De Novo Donor-Specific Antibodies
American Journal of Transplantation 2013; 13: 485 492 Wiley Periodicals Inc. Brief Communication C Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons
More informationPediatric Kidney Transplantation
Pediatric Kidney Transplantation Vikas Dharnidharka, MD, MPH Associate Professor Division of Pediatric Nephrology Conflict of Interest Disclosure Vikas Dharnidharka, MD, MPH Employer: University of Florida
More informationShould red cells be matched for transfusions to patients listed for renal transplantation?
Should red cells be matched for transfusions to patients listed for renal transplantation? Dr M.Willicombe Imperial College Renal and Transplant Centre, Hammersmith Hospital Should red cells be matched
More informationProgressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes
http://www.kidney-international.org & 2011 International Society of Nephrology see commentary on page 1254 Progressive histological damage in renal allografts is associated with expression of innate and
More informationAPHERESIS FOR DESENSITIZATION OF NON-RENAL TRANSPLANTS
APHERESIS FOR DESENSITIZATION OF NON-RENAL TRANSPLANTS GOW AREPALLY, MD MEDICAL DIRECTOR DUKE THERAPEUTIC APHERESIS SERVICE ASSOCIATE PROFESSOR, MEDICINE AMERICAN SOCIETY FOR APHERESIS MAY 25 TH 2013 OVERVIEW
More informationDesensitization in Kidney Transplant. James Cooper, MD Assistant Professor, Kidney and Pancreas Transplant Program, Renal Division, UC Denver
Desensitization in Kidney Transplant James Cooper, MD Assistant Professor, Kidney and Pancreas Transplant Program, Renal Division, UC Denver Organ Shortage Currently there are >90,000 patients on the kidney
More informationABO blood group-incompatible living donor kidney transplantation: a prospective, single-centre analysis including serial protocol biopsies
Nephrol Dial Transplant (2009) 24: 298 303 doi: 10.1093/ndt/gfn478 Advance Access publication 26 August 2008 Original Article ABO blood group-incompatible living donor kidney transplantation: a prospective,
More informationPulmonary AMR Therapeutic Options & Strategies: The Old and the New. Ramsey Hachem, MD March 28, 2017
Pulmonary AMR Therapeutic Options & Strategies: The Old and the New Ramsey Hachem, MD March 28, 2017 Disclosures Ramsey Hachem I have no financial relations with any relevant commercial interests I will
More informationTransplantation: Year in Review
Transplantation: Year in Review Alexander Wiseman, MD Medical Director, Kidney and Pancreas Transplant Program Associate Professor, Division of Renal Diseases and Hypertension University of Colorado Outline:
More informationMedicine OBSERVATIONAL STUDY
Medicine OBSERVATIONAL STUDY Clinical Significance of HLA-DQ Antibodies in the Development of Chronic Antibody-Mediated Rejection and Allograft Failure in Kidney Transplant Recipients Hyeyoung Lee, MD,
More informationConsidering the early proactive switch from a CNI to an mtor-inhibitor (Case: Male, age 34) Josep M. Campistol
Considering the early proactive switch from a CNI to an mtor-inhibitor (Case: Male, age 34) Josep M. Campistol Patient details Name DOB ESRD Other history Mr. B.I.B. 12 January 1975 (34yo) Membranous GN
More information2017 BANFF-SCT Joint Scientific Meeting. Personalized Medicine in Liver Transplantation
2017 BANFF-SCT Joint Scientific Meeting Personalized Medicine in Liver Transplantation Miquel Navasa Liver Transplant Unit. Hospital Clínic. Barcelona. Barcelona, March 2017 Disclosures Consultant for
More informationOverview of New Approaches to Immunosuppression in Renal Transplantation
Overview of New Approaches to Immunosuppression in Renal Transplantation Ron Shapiro, M.D. Professor of Surgery Surgical Director, Kidney/Pancreas Transplant Program Recanati/Miller Transplantation Institute
More informationIncidence of Rejection in Renal Transplant Surgery in the LVHN Population Leading to Graft Failure: 6 Year Review
Incidence of Rejection in Renal Transplant Surgery in the LVHN Population Leading to Graft Failure: 6 Year Review Jessica Ludolph 1 Lynsey Biondi, MD 1,2 and Michael Moritz, MD 1,2 1 Department of Surgery,
More information3/6/2017. Prevention of Complement Activation and Antibody Development: Results from the Duet Trial
Prevention of Complement Activation and Antibody Development: Results from the Duet Trial Jignesh Patel MD PhD FACC FRCP Medical Director, Heart Transplant Cedars-Sinai Heart Institute Disclosures Name:
More informationMonoclonal Gammopathies and the Kidney. Tibor Nádasdy, MD The Ohio State University, Columbus, OH
Monoclonal Gammopathies and the Kidney Tibor Nádasdy, MD The Ohio State University, Columbus, OH Monoclonal gammopathy of renal significance (MGRS) Biopsies at OSU (n=475) between 2007 and 2016 AL or AH
More informationDE-MYSTIFYING THE BLACK BOX OF TRANSPLANT IMMUNOLOGY
2016 DE-MYSTIFYING THE BLACK BOX OF TRANSPLANT IMMUNOLOGY James H Lan, MD, FRCP(C), D(ABHI) Clinical Assistant Professor, University of British Columbia Nephrology & Kidney Transplantation, Vancouver General
More informationWhy we need a new paradigm in immunosuppression USHERING A NEW ERA OF IMMUNOSUPPRESSION. Causes of death and graft loss after kidney transplantation
USHERING A NEW ERA OF IMMUNOSUPPRESSION Flavio Vincenti 45 35 AR 3 (%) 25 15 5 35.7 Why we need a new paradigm in immunosuppression Incidence of early acute rejection episodes ( 6 months) 43.7 27.4 17.9
More informationThe Histology of Solitary Renal Allografts at 1 and 5 Years After Transplantation
American Journal of Transplantation 2011; 11: 698 707 Wiley Periodicals Inc. C 2010 CSIRO C 2010 The Authors Journal compilation C 2010 The American Society of Transplantation and the American Society
More informationDebate: HLA matching matters in children
Annual Congress 2018 14 th to 16 th March, the Brighton Centre, Brighton Debate: HLA matching matters in children Presenting the case for - Dr Jon Jin (JJ) Kim, Nottingham Richard & Ronald Herrick 23 Dec
More informationSince the first Banff meeting in 1991, the diagnosis and
CLINICAL AND TRANSLATIONAL RESEARCH Acute Cellular Rejection: Impact of Donor-Specific Antibodies and C4d Michelle Willicombe, 1,5 Candice Roufosse, 2 Paul Brookes, 3 Adam G. McLean 1, Jack Galliford,
More information