state of pediatric kidney transplantation
TRANSCRIPT
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State of Pediatric Kidney State of Pediatric Kidney TransplantationTransplantation
Vikas Dharnidharka, MD, MPHMedical Director, Pediatric Kidney
TransplantationUniversity of Florida
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ObjectivesObjectives
• To understand unique aspects of pediatrickidney transplantation
• To review the state of pediatric kidney transplantation in the USA
• To inform you about our current initiatives and research at our center
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Common aspects in adult and pediatric Common aspects in adult and pediatric kidney transplantkidney transplant
• Transplant offers a survival advantage over the long-term and better quality of life
• Work up of donor and recipient mostly the same
• Allocations also through UNOS• Most surgical aspects are similar, though not
all• Medications used are identical• Many complication issues are similar
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Unique aspectsUnique aspects• Smaller volumes per center than in adults (10-30/year versus
50-300/year)• Therefore, pediatricians need multicenter data• Very different primary causes of end-stage renal disease• Allocation issues for pediatrics• Surgical issues• Drug metabolism issues• Work up differences• Vaccinations• Graft and patient survival results• Complications and outcomes:
– Growth– Infections– Post-transplant lymphoproliferative disease (PTLD)
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Data SourcesData Sources
• United Network of Organ Sharing (UNOS) and Scientific Registry of Transplant Recipients (SRTR)
• North American Pediatric Kidney Transplant Cooperative Studies (NAPRTCS)
• Stanford University• University of Florida and Shands Transplant
Center
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Primary Diagnosis by AgePrimary Diagnosis by Age
0102030405060708090
100
0-1 2-5 6-12 >12Patient Age (Years)
Perc
ent
FSGS GN Other Structural
Compare to adults, where diabetes and hypertension are the two leading causes of ESRD
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AllocationAllocation
• Pediatric recipients need to live longer with their transplant
• May need multiple transplants over their lifetimes• UNOS always had preferential schemes for pediatric
kidney, but prior systems did not work• October 2005: new system
– Deceased donors <35 years age, relative priority to pediatric patients after 0 antigen mismatch, highly sensitized patients PRA > 80%, or kidney plus other organ combined transplant
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Drop in waiting time
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Jump in proportion of deceased donors
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Surgical issuesSurgical issues• Thrombosis rate by recipient age group
– < 2 years of age 9.0% – 2-5 years: 5.5% – 6-12 years: 4.4% – > 12 years: 3.5% (P=0.01)
• Thrombosis rate by donor age group– < 5 years age 8.3% – 5-10 years: 4.5% – > 10 years: 3.2% (P<0.001)
• Practice changed: avoid small kidneys to small recipients; perform en bloc instead (superior results)
Singh et al, Transplantation, 1997Dharnidharka. AJT, 2006
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Day 30 Maintenance MedicationsDay 30 Maintenance MedicationsPrednisone CyclosporineTacrolimus AzathioprineMMF Sirolimus
Perc
ent
0
20
40
60
80
100
Transplant Year
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Recent drop in chronic steroid use
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Drug metabolism in pediatricsDrug metabolism in pediatrics
• Immunosuppressive agents are metabolized much faster in very young children
• CsA may need to be given three times a day, not twice
• Sirolimus may need to be given twice daily, not once a day
• MMF marrow toxicity can be worse in absence of concomitant steroids
Filler et al, Schachter et al
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Causes of Graft Failure 1987Causes of Graft Failure 1987--20042004
Cause of Index Subsequent TotalGraft Failure n=2123 n=291 n=2414Chronic Rejection 571 (33%) 101 (35%) 811 (34%)Acute Rejection 277 (13%) 39 (13%) 316 (13%)Thrombosis 220 (10%) 36 (12%) 256 (11%)Death 199 (9%) 22 (8%) 221 (9%)Recurrence 138 ( 7%) 28 (10%) 166 ( 7%)Other 718 (34%) 65 (22%) 644 (27%)
NAPRTCS, 2002
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1987-19901991-19941995-19981999-20022003-2007
Perc
ent R
ejec
tion
0
20
40
60
80
100
Months from Transplant
0 12 24 36 48
0
20
40
60
80
100
Time to First Rejection for Index TransplantsTime to First Rejection for Index Transplants
Living Donor
Slope identical after red line
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1987-19901991-19941995-19981999-20022003-2007
Perc
ent R
ejec
tion
0
20
40
60
80
100
Months from Transplant
0 12 24 36 48
0
20
40
60
80
100
Time to First Rejection for Index TransplantsTime to First Rejection for Index Transplants
Deceased Donor
Slope not as identical, especially for recent cohort
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Graft SurvivalGraft Survival
Living Donor (1987-1995)Living Donor (1996-2007)Deceased Donor (1987-1995)Deceased Donor (1996-2007)
Per
cent
Gra
ft S
urvi
val
30
40
50
60
70
80
90
100
Years From Transplant
0 1 2 3 4 5 6 7
30
40
50
60
70
80
90
100
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Worse graft survival in adolescents, also true for living donor
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FSGS and Graft SurvivalFSGS and Graft Survival
Baum, KI, 2001
Loss of living donor advantage in FSGS
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Patient SurvivalPatient Survival
Living Donor (1987-1995)Living Donor (1996-2007)Deceased Donor (1987-1995)Deceased Donor (1996-2007)
Per
cent
Pat
ient
Sur
viva
l
70
80
90
100
Years from transplant
0 1 2 3 4 5 6 7
70
80
90
100
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CreatinineCreatinine ClearanceClearance
0-1 years2-5 years6-12 years>12 years
Cal
cula
ted
clea
renc
e
50
60
70
80
90
100
110
120
Years from Transplant
0 1 2 3 4 5 6 7
0-1 years2-5 years6-12 years>12 years
Cal
cula
ted
clea
renc
e
50
60
70
80
90
100
110
120
Years from Transplant
0 1 2 3 4 5 6 7
Living Donor Deceased Donor
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0-1 years2-5 years6-12 years>12 years
Hei
ght Z
Sco
re
-2.5
-2.0
-1.5
-1.0
-0.5
Years from Transplant
0 1 2 3 4 5 6
-2.5
-2.0
-1.5
-1.0
-0.5
HEIGHT Z SCORE
Standardized Score (mean + SE)By Age at Transplant
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Infections as ComplicationsInfections as Complications
0
5
10
15
20
25
30
35
1-6 Months 6-24 Months 1-6 Months 6-24 Months
RejectionViralAll Infection
Dharnidharka, AJT, 20041987 2000
%
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Causes of DeathCauses of DeathTotal Living Donor Deceased Donor
N %
Functio-inggraft N %
Function-inggraft N %
Function-inggraft
All deceased patients 546 100.0 256 242 100.0 119 304 100.0 137
Cause of Death
Infection,Viral 44 8.1 23 24 9.9 13 20 6.6 10
Infection,Bacterial 69 12.6 34 33 13.6 15 36 11.8 19
Infection, Not Specified 43 7.9 14 22 9.1 7 21 6.9 7
Cancer/malignancy 58 10.6 40 32 13.2 23 26 8.6 17
Cardiopulmonary 84 15.4 39 30 12.4 15 54 17.8 24
Hemorrhage 33 6.0 12 9 3.7 2 24 7.9 10
Recurrence 10 1.8 1 4 1.7 1 6 2.0 0
Dialysis-relatedComplications 16 2.9 0 8 3.3 0 8 2.6 0
Other 136 24.9 67 61 25.2 33 75 24.7 34
Unknown 53 9.7 26 19 7.9 10 34 11.2 16
Infections together = 28.6%, plus malignancies = 39.2%These likely represent overimmunosuppression complications
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• Big recent increase in number of recommended vaccines• Variable response to immunizations in ESRD• Increased risk with live virus vaccines post-transplantation• Fully immunize prior to transplantation as far as possible
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PTLDPTLDTime to LPD by Era of Transplant
Era of transplant 1987-19921993-19971998-20022003-2006
Per
cent
with
LP
D
0
5
10
15
20
Months from transplant
0 12 24 36 48 60 72 84
•PTLD rate in pediatric kidney transplantation: rose from < 1 to > 3% over the years•PTLD rate in adult kidney transplantation: stayed < 1%•Highest risk factor is EBV donor/recipient mismatch (D+/R-)•Get EBV donor and recipient serology pre-transplant!
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SteroidSteroid--free resultsfree results
Better growth
Better GFR
Sarwal, Transplantation, 2003
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CCTPTCCTPT• Cooperative Clinical Trials in Pediatric
Transplantation• NIH grant mechanism for multi-center transplant
clinical trials and mechanistic studies, in children• Started in 1994
– IN01 (1994-1999): completed, presented and published– SW01 (1999-2004): completed and presented– SNS01 (2004-2009): data will be presented in 2 months
• Latest:– CTOT-2: looking at post-transplant donor specific antibody
production and pre-emptive rituximab– CTOT-C: just funded
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University of Florida Pediatric Kidney University of Florida Pediatric Kidney Transplant ProgramTransplant Program
• Continuously active since early 1970s• We are the only CCTPT participating center in
Florida• We are an above-average volume center, historically
13-15 transplants/year• We offer a steroid-free protocol as standard of care• Short waiting times• Have patients from throughout the state, work with
all groups