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Long term outcome after renal transplantation Influence of donor & recipient risk factors and the choice of immunosuppression. T H Mathew , SP McDonald & GR Russ ANZDATA Registry & Renal Unit, The Queen Elizabeth Hospital Adelaide. September, 2001. - PowerPoint PPT Presentation
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Long term outcome after renal transplantation
Influence of donor & recipient risk Influence of donor & recipient risk factors and the choice of factors and the choice of
immunosuppressionimmunosuppression
TH Mathew, SP McDonald & GR Russ
ANZDATA Registry & Renal Unit,
The Queen Elizabeth Hospital Adelaide. September, 2001
Source of data – ANZDATA & ANZOD
• Australia & New Zealand Dialysis & Transplant (ANZDATA) Registry – A voluntary registry documenting the outcome of all
dialysis & transplant patients in Aus & NZ since 1965– 100% reporting and follow-up of ~24,000 patients
• Australia & New Zealand Organ Donor (ANZOD)Registry– Has acquired donor information since 1988
• Registries co-located
Long term outcome in renal transplantation
• The short term (1yr) outcome has improved substantially in recent times
• The long term outcome beyond 5 yrs has been little studied
• This study aims to assess the influence of various factors on long term graft (& patient outcome)
• All data is from ANZDATA and ANZOD Registries.
Australia CD1. One year survival 1975-99
30
40
50
60
70
80
90
100
75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99
% s
urv
iva
l
Graft
Patient
Predictive patient & donor characteristics significantly affecting 1yr survival on multivariate
analysis (0n 1993-8 cohort) – Briganti et al
• Donor age p=0.000• HLA mismatches p=0.000• Vascular disease p=0.002• Time on dialysis p=0.004• Year of transplant
p=0.008• Allograft source p=0.044
Long term outcome in renal transplantation
• The short term (1yr) outcome has improved substantially in recent times
• The long term outcome in CD1 & LD1 recipients beyond 5 yrs has been little studied
• This study aims to assess the influence of various factors on long term graft (& patient outcome)
Australia primary patient & graft (CD & LD) survival 1970-94. n = 7623 grafts
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
% s
urvi
val
PatientGraft
Australia primary graft (CD & LD) survival 1970-94. n = 7623 grafts. The decay is exponential.
y = 84.395e-0.065x
R2 = 0.9993
10
20
30
40
50
60
70
80
90
100
2 4 6 8 10 12 14 16 18 20 22 24
% s
urv
ival
Graft
Expon.(Graft)
Australia primary graft survival 1970-94. n = 7623 grafts
0
20
40
60
80
100
% g
raft
su
rviv
als
Graft
Graft (+censor)
1.8%/yr
2.7%/yr
5 Yr+ survival for primary grafts (n= 4353) Australia (1970-94)
0
20
40
60
80
100
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
% s
urv
ival
Patient
Graft
4.3%/yr
3.2%/yr
Patient survival after 5 yrs (Aus CD1 & LD1) by selected time periods – the death rate has declined
50
60
70
80
90
100
5 6 7 8 9 10 11 12 13 14 15Years
% S
urv
ival
1970-74 (440)
1975-84 (1266)
1985-89 (1231)
1990-94 (1415)
~3.3-3.7%/yr
The death rate/100 patient years for primary renal grafts beyond 5 yrs is reducing in recent years
4.56
3.61 3.38
0
1
2
3
4
5
Dea
th r
ate
1970-84 1985-89 1990-94
Death rate/100 patient years >5yrs post graftAustralia CD1 & LD1 by period
2.25
1.06
0.540.71
1.42
0.650.49
0.340.5
1.92
0.850.82
0
0.5
1
1.5
2
2.5
Cardio-Vasc Malignancy Infection Other
Dea
th R
ate
1970-84
1985-89
1990-94
Graft survival beyond 5 yrs (Aus CD1 & LD1). The decline is the same in each selected time period
40
50
60
70
80
90
100
5 6 7 8 9 10 11 12 13 14 15
Years
% s
urv
ival
1970-74 (440)
1975-84 (1266)
1985-89 (1231)
1990-94 (1415)
40
50
60
70
80
90
100
5 6 7 8 9 10 11 12 13 14 15
Years
% s
urv
ival
1970-74 (440)
1975-84 (1266)
1985-89 (1231)
1990-94 (1415)
4.8%/yr
Death censored graft fail rate/100 graft/yrs > 5yrs post has increased 33% since 1984
CD1& LD1 Australia
6.63
2.69
6.38
3.35
2
3
4
5
6
7
8
Graft fail rate Death censored graft fail rate
Ra
te/1
00
pt
yrs
1970-84 (1706)
1985-94 (2644)
Cause of graft failure rate The loss from ‘chronic rejection’ is increased in
recent times
3.943.04
2.542.33
0.810.36
0
2
4
6
8
1970-84 (1706) 1985-94 (2644)
graf
ts fa
il/10
0 pt
/yrs
Other
Ch Rejection
Death
Predictive characteristics favoring primary graft survival beyond 5yrs
Significant factors on univariate analysis
• Donor source LD p=0.0002• Donor age <50yr p=0.0002• Donor not ‘marginal’ p=0.002• Donor death trauma p=0.02• Recipient never smoked p=0.0001• Not on CsA at 2 & 5yrs. P=0.0004
Predictive characteristics favoring primary graft survival beyond 5yrs
Non –significant factors on univariate analysis
• Donor hypertensive• Donor oliguric• Donor terminal creatinine >120umol/l • Donor smoked• CsA dose >5mg/kg/d• Primary renal disease• Use of Ab for rejection in 1st 6m• Delayed graft function >7d
Effect of donor source on graft outcome >5yrs (Aus CD1 1985-94 – 2646 grafts)
50
60
70
80
90
100
5 6 7 8 9 10 11 12Years
% S
urvi
val
Cadaver
Live Donor
p <0.0002
5.4%/yr
4%/yr
Effect of donor age on graft outcome >5yrs (Aus CD1 1985-94 – 2646 grafts)
40
50
60
70
80
90
100
5 6 7 8 9 10 11 12 13 14Years
% g
raft
su
rviv
al
Donor <50yrs
Donor >50yrs
p <0.0002
5.4%/yr
4.7%/yr
Effect of recipient smoking on graft outcome >5yrs (Aus CD1 1985-94 – 2646 grafts)
50
60
70
80
90
100
5 6 7 8 9 10Years
% g
raft
sur
viva
l
Never (751)Former (304)Current (142)
p <0.0001 (former v never)
7.8%/yr
7%/yr
5.4%/yr
Graft survival on CsA is reduced >5yrs (Aus CD1 & LD1 n=4009)
50
60
70
80
90
100
5 6 7 8 9 10 11 12 13 14
% g
raft
su
rviv
al
On CsA
No CsA
3.8%/yr
5.3%/yr
p <0.0000
Graft survival (death censored) 5yrs +CsA & no CsA (Aus CD1 & LD1)
50
60
70
80
90
100
5 6 7 8 9 10 11 12 13 14
% s
urv
iva
lss
On CsA
No CsA
3.4%/yr
2.1%/yr
p <0.0000
Predictive characteristics favoring primary graft survival beyond 5yrs
Significant factors on univariate analysis
• Donor source LD* p=0.0002• Donor age <50yr* p=0.0002• Donor not ‘marginal’ p=0.002• Recipient never smoked* p=0.0001• Donor death trauma p=0.02• Not on CsA at 2 & 5yrs* p=0.0004
* Retained significance on multivariant analysis
Multivariate analysis of factors affecting death censored primary graft outcome >5yrs
Significant factorsHR (CI)
• On CsA 1.9 (1.4-2.6)• Recipient smoking 1.86 (1.3-2.6)• Recipient <20yrs 1.55 (1.1-2.1)• Donor Age >50yrs 1.51 (1.2-2.0)• Recipient >50yrs 0.61 (0.5-0.8)• Live donor 0.67 (0.4-1.00)
Multivariate analysis of factors affecting death censored primary graft outcome >5yrs
Non -Significant factors
• Mismatch on HLA• Marginal donor status• Vascular disease at entry• Year of transplant• Cause of donor death
The effect of CsA on long term graft (death censored) outcome
• Is statistically and clinically significant : - – 10% difference over ten yrs– Most evident in those with S Cr <140umol/L at 1 yr
• Not accounted for by – donor source or quality– vascular disease pre entry
• The patients on CsA had– worse matching (-)– more recipients >50yrs (+)– more marginal donors (-)– more smokers (-)
(all marginally significant)
European Multicenter trial (Transpl Proc 25:527, 1993)
Data redrawn with 5yr survival adjusted to 100%. (ITT)
60
70
80
90
100
5yrs 6 7 8 9 10
% s
urv
iva
l
CsA (n=117)
Aza/Pred (n=115)
4%/yr
2.2%/yr
Conclusions on graft loss beyond 5 years
• Grafts fail after 5 years through1. Death. The death rate is currently decreasing & now
accounts for 48% of losses2. Graft failure. The rate of loss is increasing due to an
increase in ‘chronic rejection’ & ‘other’ causes
• Increased risk of late graft loss (death censored) with– Continuing exposure to CsA, donor age >50yrs,
recipient age <20yrs, recipient smoking
• Decreased risk of late graft loss (death censored) with– Recipients >50yrs, live donors