Paediatric Renal TransplantationDr Heather MaxwellConsultant Paediatric NephrologistRoyal Hospital for Sick ChildrenGlasgow

Paediatric Renal Transplantation

Background informationOutcome of transplantationWork up for transplantationAccess to transplantation

Renal TransplantationFirst human to human renal transplant was in 1933The first successful adult renal transplant was performed in Boston in 1954 in twinsFirst paediatric renal transplant performed in 1959 from identical twin sisterFirst in Yorkhill was 1977 and 204 transplants have now been performed since

Paediatric Renal Transplant OutcomePatient survival Graft survivalParameters of GrowthBPHaemoglobin

Factors affecting outcomeRHSC AuditsNHSBT ODT (UKT)Centre-specific dataCohort studies20 year review of paediatric renal TxRenal Registry

Paediatric Renal Transplant Program RHSC Glasgow

High incidence of vascular thromboses Lower graft survival data than expectedChange in practiceJoint adult transplant and paediatric urologistsMulti-disciplinary team approachTransplant work-up and protocolResults of Audit from 1990s

Paediatric Renal Transplant Program RHSC Glasgow

UK Paediatric Renal Transplant Data NHSBTwww.uktransplant.org.uk

RHSC Glasgow DataNHSBTwww.uktransplant.org.uk

RHSC Audit 1998-2007Female37%Male63%37 LRD (46%)43 DD (54%)

Cause of RenalFailure

RHSC Audit 1998-2007

1998-2007 RHSC Audit - Outcome

Audit 2008-2011Higher incidence of graft thrombosis and vascular complications than expectedParticularly with LRD transplantsM&M reviewsSmall number of transplantsHigh risk patients

RHSC Audit Surgical Complications* 3 grafts lost

RHSC Audit Medical Complications* 16 (55%) biopsied

Current ImmunosuppressionTacrolimusMycophenolate MofitilTreatment ArmDaclizumabPrednisolone for 5 daysControl ArmStandard prednisoloneGrenda et al, 2010

Treatment ArmControlGraft Survival97%97%BPAR10%7%Growth0.17SD0.04SDAdverse Glucose Metabolism3%16%

Rejection RateNAPRTCS Report 2007

Probability of First Rejection at 12 MonthsTransplant YearLIVING DONORDECEASED DONOR%SE%SE1987-9054.11.769.31.41991-9445.81.561.01.51995-9833.61.342.51.61999-0222.91.326.91.72003-0613.71.517.91.7

2008-2011 RHSC Audit - Outcome

Audit 2008-2011Higher incidence of graft thrombosis and vascular complications than expectedParticularly with LRD transplantsM&M reviewsSmall number of transplantsHigh risk patientsInternal and external reviewChange in practice smaller group of surgeons involved

Factors Affecting Outcome of Paediatric Renal Transplantation

Factors Affecting Outcome of Paediatric Renal TransplantationAn analysis of deceased donor paediatric renal transplants performed in the UK between 1986 and 1995 found that extremes of donor age, young recipient age and poor HLA matching were the major factors which adversely affected transplant outcome

Avoided transplants in the very youngOnly used donors aged 5-50 yearsBetter matchingPostlethwaite et al, 2002

To investigate the influence of a variety of factors on five-year renal transplant survival in a more recent cohort of paediatric recipients 1995-2001To compare risk-adjusted outcome of adult and paediatric recipients at five years post-transplant7946 transplants (596 paediatric & 7350 adult)UKT Study 1995 - 2001Maxwell et al, 2006WTC 2006

Cox regression analysis of factors influencing five-year transplant survival (time from transplant to earlier of graft failure or patient death)

Factors considered in the analysis:Methods

Donor factorsRecipient factorsOther factorsAgeAgeAge matchCause of deathPrimary renal diseaseHLAEthnicityRegistration waiting timeShippingGenderEthnicityKidney damageCMVGenderGraft yearCMVSensitisationResidual sensitisation

Cox regression analysis of factors influencing five-year transplant survival (time from transplant to earlier of graft failure or patient death)

Factors considered in the analysis:Methods

Donor factorsRecipient factorsOther factorsAgeAgeAge matchCause of deathPrimary renal diseaseHLAEthnicityRegistration waiting timeShippingGenderEthnicityKidney damageCMVGenderGraft yearCMVSensitisationResidual sensitisation

SummarySignificant year-on-year improvement in transplant outcome of paediatric patients

5-year transplant survival of paediatric patients by year of transplant

Improved Acute Graft SurvivalBetter pre-transplant managementImproved anaesthetic and operative careBetter organ selectionSizeMatchingUse of more living donorsOrgan preservation and reduced cold ischaemia time (

SummarySignificant year-on-year improvement in transplant outcome of paediatric patientsVery young donors (0 10 years) and donors aged over 40 years confer the greatest risk of transplant failure in paediatric patients

5-year transplant survival of paediatric patients by donor age group

SummarySignificant year-on-year improvement in transplant outcome of paediatric patientsVery young donors (0 10 years) and donors aged over 40 years confer the greatest risk of transplant failure in paediatric patientsGlomerulonephritis is associated with poorer outcome than other primary renal diseases

5-year transplant survival of paediatric patients by primary renal disease group

SummarySignificant year-on-year improvement in transplant outcome of paediatric patientsVery young donors (0 10 years) and donors aged over 40 years confer the greatest risk of transplant failure in paediatric patientsGlomerulonephritis is associated with poorer outcome than other primary renal diseasesRisk of transplant failure associated with adolescents (14 17 years) similar to that for recipients aged over 60 years

5-year transplant survival by recipient age all patients

5-year transplant survival by recipient age

2006 Allocation SchemeIncreased availability of well-matched organs for childrenImproved access for long waitersIncreased access for homozygous patientsReduce shipping times

Still use deceased donors 5-50yrs Paediatric donors would no longer preferentially given to paediatric recipientsAvoid very small recipients

UK PAEDIATRIC KIDNEY TRANSPLANTATION:A 20-YEAR REVIEW

Lisa Mumford, Jane TizardOn behalf of the Kidney Advisory Group Paediatric Subgroup

Deceased and living paediatric kidney only transplantsNumber of transplantsYear of graft

Deceased donors aged between 5 and 50 yearsNumber of donorsYear of donation

Donor age of deceased paediatric kidney only transplantsDonor ageYear of graft

HLA mismatch levels of deceased paediatric kidney only transplant patientsProportion of transplantsYear of graft

HLA mismatch levels of deceased paediatric kidney only transplant patients

Waiting times of UK deceased paediatric kidney only transplantsWaiting time (days)Year of graft

Waiting Times for Listed Patients2000 2002:median 153 days (95% CI: 119-187) 2003 2005median 264 days (95% CI: 201-327) 2006 2008median 374 days (95% CI: 285-463)

In terms of the impact of the 2006 scheme on equity for paediatric patients, the number on the transplant list and the median waiting time have remained unchanged while the number of transplants for long-waiting patients has increased as a result of a change made in April 2008 such that only 3% of listed patients have been waiting in excess of 3 years compared to 12% in December 2005.

Waiting times of deceased paediatric kidney only transplants

Recipient ethnicity of deceased paediatric kidney only transplant patientsProportion of transplantsYear of graft 2010 34% ethnic minority patients registered on transplant list

Sensitisation (cRF) of first deceased paediatric kidney only transplant patientsProportion of transplantsYear of graft 2010 48% patients with cRF 11-100 registered on transplant list

Sensitisation (cRF) of first deceased paediatric kidney only transplant patients

Cold ischaemia time (hours) of DBD paediatric kidney only transplantsCold ischaemia time (hours)Year of graft

Cold ischaemia time (hours) of DBD paediatric kidney only transplants

Reported immunosuppression following deceased paediatric kidney only transplant (3mth)Proportion of transplantsYear of graft S=SteroidA=AzathioprineM=MycophenolateC=CyclosporinT=Tacrolimus

Graft survival following first DBD paediatric kidney only transplant2006-2010 1yr survival 95% (92-97) N=3082001-2005 5yr survival 81% (77-85) N=3601996-2000 10yr survival 63% (58-68) N=4111991-1995 15yr survival 45% (41-50) N=4881986-1990 20yr survival 27% (23-31) N=442p

Graft survival following first DBD paediatric kidney only transplantexcluding failures within the first year2001-2005 5yr survival 88% (84-91) N=3281996-2000 10yr survival 73% (68-78) N=3451991-1995 15yr survival 55% (50-60) N=3921986-1990 20yr survival 38% (32-44) N=310p

Graft survival following first living paediatric kidney only transplant2006-2010 1yr survival 97% (94-98) N=2862001-2005 5yr survival 91% (86-95) N=1981996-2000 10yr survival 74% (64-81) N=1161991-1995 15yr survival 45% (32-58) N=671986-1990 20yr survival 35% (20-50) N=47p=0.008

Graft survival following first living paediatric kidney only transplantexcluding failures within the first year2001-2005 5yr survival 95% (90-97) N=1731996-2000 10yr survival 78.0% (68-85) N=1071991-1995 15yr survival 49% (34-62) N=601986-1990 20yr survival 37% (22-53) N=42p=0.009

Graft survival following first paediatric kidney only transplant5 yr survival10 yr survival20 yr survival

Living 88 (85 - 91) 71 (65 - 76) 48 (38 - 58)(n=714) p

Graft survival following first paediatric kidney only transplant5 yr survival10 yr survival20 yr survival

Living 88 (85 - 91) 71 (65 - 76) 48 (38 - 58)(n=714) p

Graft survival following first DBD paediatric kidney only transplant

UK Renal RegistryPaediatric Data

UK Paediatric Renal RegistryUK Renal Registry Report 2010

UK Paediatric Renal RegistryUK Renal Registry Report 2010Current RRT treatment used by prevalent

Pre-emptive TransplantationNHSBTTransplant Activity in the UK, 2010-11

UK Paediatric Renal RegistryUK Renal Registry Report 2010

UK Paediatric Renal RegistryUK Renal Registry Report 2010Median HtSDS in pts receiving RRT from1999-2009 with % receiving rhGHMedian systolic BP SDS in transplant pts in 2009

UK Paediatric Renal Registry% Patients achieving thehaemoglobin standard in 2009Hb standard by MMF use 1999-2009Hb standard by GFR 1999-2009UK Renal Registry Report 2010

Transplant Work Up

The Transplant Team SurgeonTissue TypingNephrologistSpecialist renalnursesSocial worker DietitianRadiologistPsychologistsTransplantCo-ordinatorTeacher

Pre-Transplant ManagementAttention to nutrition, growth, BP, proteinuriaPre-transplant work-upBlood vesselsEchocardiogramVirology (CMV, EBV, Varicella)BladderPsychology, educationHLA antibodiesPlan for operation

Transplant ProcedureTransplant surgeon and paediatric urologistAnaesthetistPaediatric nephrologistPatient data easily accessible to all staff

Patient well hydratedEarly doppler USS if concerns re thrombosisClose monitoring in ITU

Current ImmunosuppressionTacrolimusMycophenolate MofitilTreatment ArmDaclizumabPrednisolone for 5 daysControl ArmStandard prednisoloneGrenda et al, 2010

Treatment ArmControlGraft Survival97%97%BPAR10%7%Growth0.17SD0.04SDAdverse Glucose Metabolism3%16%

Access to Transplantation

Access to transplantationCriteria for suitable recipientAge / sizeSensitisation

Pre-emptive transplantationVirtual cross-match

ABO IncompatibilityPaired donation

HLA Match

HLA-A phenotype frequencies in 10 000 UK cadaver kidney donorsUK Transplant 09/03% donors

ABOi TransplantsGroup A consists of 2 types A1 and A2A2 is less antigenic than A1A1>B>A2Group O patients have higher titres of antibodiesAnti-A titres are higher than anti-B titresTitres of 1 in 8 or 1 in 16 are lowNo additional treatment necessary for low titre antibodies which do not appear to pose an additional risk

ABOi Transplants

ABOi TransplantsRecipientDonorRecipientDonor

*Thank you for asking me to talk about our experience of paediatric renal transplantation at Yorkhill. *However what can our patients expect when they receive a renal transplant?*As an exampleReduced ARR is associated with better graft survival and better graft function*Some of these are evidence based others are more difficult to prove*There are two main aspects to the management pre-transplant. One is to have the child as well as possible to be able to deal with the rigours of the operation and immunosuppression and the other is to gather as much information as possible so as to be able to plan the operation and treatment without any nasty surprises. We need to know if the child is prone to viral infections EBV CMV etc, if the vessels are normal, if the bladder is safe.