experiência brasileira em dessensibilizacão pré-transplante renal. maria cristina ribeiro de...
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Maria Cristina Ribeiro de CastroServiço de Transplante Renal e Laboratório de
Imunologia do Incor – FMUSPHospital Samaritano - SP
Pacientes em Tratamento Dialítico no Brasil1974 - 2008
0
20000
40000
60000
80000
100000
87.044
Dialysis cost in Brazil: R$ 2 million (without drugs and hospitalizations)
Jan/2009: 77.589 in dialysis
- 30.419 (39,2%) on the WL - 42,8% with Hb<11 g/dL, 50% with Phos>5- Mortality rate: 17% per year.
Months N. Pt N. Deaths Death probability Pt survival Actuarial survival
0 – 12 186 37 0,1989 (19,89%) 0,8011 (80,11%) 0,8011 (80,11%) 12 – 24 123 14 0,1138 (11,38%) 0,8862 (88,62%) 0,7099 (70,99%) 24 – 36 91 12 0,1318 (13,18%) 0,8682 (86,82%) 0,6163 (61,63%) 36 – 48 63 8 0,1269 (12,69%) 0,8731 (87,31%) 0,5380 (53,80%) 48 – 60 46 5 0,1086 (10,86%) 0,8914 (89,14%) 0,4795 (47,95%) 60 – 72 27 5 0,1851 (18,51%) 0,8149 (81,49%) 0,3907 (39,07%) 72 – 84 15 1 0,0666 (6,66%) 0,9334 (93,34%) 0,3646 (36,46%) 84 – 96 6 2 0,3333 (33,33%) 0,6667 (66,67%) 0,2430 (24,30%)
SES-SP: 1/1/2005-1/1/2011 (4644 tx performed)Mortality on the WL: 7,22 % per yearMedian waiting time for a non-sensitized pt: 30 m
283 TX (6%): 0 MM (A,B,DR)
25,6% of listed patients with PRA >10%
11,4% of listed patients with PRA >50%
6% of listed patients with PRA > 80% (2051 pts)
2% (741 pt) on priority due to access problems
515 pts. transplanted on priority (13%)
SES-SP: 1/1/2005-1/1/2011 (4644 tx performed)
WL (25318 pt) Tx (4277 pt) - 17%
PRA No priority Priority No priority Priority
< 10% 24867 (74,7%) 451 (60,9%)
4017 (85,7%)
260 (67%),16%
10-49%
4544 (13,6%) 120 (16%) 425 (9,1%) 69 (17,7%)
50-79%
1803 (5,4%) 76 (10,3%) 154 (3,3%) 35 (8,7%)
> 80% 2051 (6 %) 94 (12,7%)
92 (2%) 26 (6,6%), 5%
SES-SP 1/1/2005 -1/1/2011
17% of the WL pts. were transplanted 16% with PRA <10%5% with PRA > 80%2 times more priority pts. In PRA > 80%
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Non- priority Priority
No sensitized
74% (N=384)
80% (N=223)
SES-SP 1/1/2005 -1/1/2011
%
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3040
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90100
0 1 to 25 26 to 50 51 to 75 76 to100
6y GS
6y GS in O MM (A, B, DR): 72% (NS)
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No priority Priority
Sensitized
71% (N=706) 56,5%
(N=144)
SES-SP 1/1/2005 -1/1/2011
%
Better transplant priority patients earlier, before they become sensitized!
P=0.0263 log-rank
Deceased donor
Living donor
Survival compared to UNOS Living Donor Deceased Donor1 year 97.6%/98% 81.7%/94%3 year 95.2%/94% 76.5%/88%5 year 90.9%/90% 70.7%/82%
N=190
(42)
(148)
Transplants performed between 1996 and 2007 - FMUSP.
Living donor
Deceased donor
P=0.8576 log rank
Survival compared to UNOS Living Donor Deceased Donor 1 year 92.7%/95% 83.5%/89% 3 year 76.1%/87% 73.5%/78% 5 year 61.6%/80% 64.2%/67%
5% lower GS for living and deceased donors compared to UNOS
N=190
(148)
(42)
To evaluate the risk of staying on dialysis To evaluate the chances to be transplanted
◦ Donation and transplant rate of the region◦ Median waiting time◦ Policy for sensitized patients (Stimulate the allocation of cross-
match negative donor kidneys to these patients). To evaluate the acceptable immunologic risk (easier w/LD) To evaluate the transplant possibilities with living and with deceased donors
◦ Resources for desensitization◦ Resources for support a high-risk patient after Tx◦ Characteristics of the patient (age, life expectation, clinical
condition)
Transplant program/Pt Protocol Pt survival Graft survival AR (%)Mean SCr
(mg/dl)
Mayo clinic/90HD IVIG
PP/LD
IVIG
95% (at 5 yr) 80% (at 5 yr) 35 1.6±0.6 (at 5 yr)
John Hopkins/90 PP/CMVIG 95% (at 3 yr) 80.9% (at 3 yr) 62 1.2±0.3 (at 3 yr)
CSMC/96
GLOTZ/02 (DD)
HD IVIG
IVIG
97% (at 5 yr)
85% (at 5 yr)
87% (at 5 yr)
70% (at 5 yr)
36
40
1.5±0.4 (at 5 yr)
Not related
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1y 3y 5y 8y
LD Dessensitized
Dialysis- only
Dialysis and DD Tx
p< 0,0001
Montgomery R, NEJM 2011 Jul 28;365(4):318-26.
Patient Survival (%)
N=457 isolated kidney transplants (2007-2009)
Global incidence (85/457): 18,6%
- Cell-mediated rejection (55/457): 12%
- Antibody-mediated rejection (30/457): 6,6%
Without vs with rejection
Cell-mediated rej. Vs Ab-mediated rej.
N=42 CMRn=28 (66%)
AMRn= 14 (34%)
p
Last Scr 1,57 (0,9-4,8) 1,67 (1-5,7) 0,70
MDRD (ml/min) 48,3 (13-75) 40,7 (11,5-81,5) 0,82
Last Scr 1,3 (0,7-6,4) 1,57 (0,9-5,7) <0,001
MDRD (ml/min) 57,3 (7,5-104) 45 (11,5-81,50 <0,0001
N=290 Without rejectionn=248 (85%)
With rejectionn=42 (15%)
p
Transplant without knowing the immunological risk
No transplant in sensitized patients No transplant in patients with DSAs No transplant in pts.with DSAs and high MFIs No transplant in positive FCXM Transplant knowing and accepting the
immunological risk (post transplant monitoring)
Before the tx: Stratify AMR risk Evaluate treatment risk/advantages
After the tx: Active monitoring and observation Early AMR diagnosis and treatment
Living donors:◦ Transplant with DSAs but with a negative T and B FCXM◦ IS: Thymoglobulin, Tacrolimus and MMF (We would use IVIG!)
Deceased donors: ◦ Transplant sensitized patients with any level of DSAs, with a
negative T and CDC-XM ◦ IS: Thymoglobulin, MMF and Tacrolimus (We would use IVIg!)◦ Perform a Single atg PRA and a renal biopsy during the first week
◦ All patients: We follow renal function, proteinuria, single atg PRA and FCXM (in LD)
during the first months We perform kidney biopsy with C4d staining when clinically indicated We treat AMR with PP and Rituximab
Include patients that have PRA higher than 70%, with more than 2 years on dialysis
Look for a living donor:◦ Low titers: IVIg (maximum of 6 doses)◦ High titers: IVIG + Rituximab or IVIG + PF
No living donors:◦ Transplant priority for vascular access problems: IVIG and
if no transplant in 3-6m, IVIG + Rituximab◦ No transplant priority: any sense to treat without priority?
Depends on the number of tested donors.
Hospital Samaritano: 9 pt desensitized (4DD, 5 LD), 2y FUT, 0 graft/pt losses.
Twenty-four patients transplanted with a previous positive IgG AHG-CDC T or B- cell CM or w/ FCXM higher than 300 channels (6 cases) against their potential donors.
All patients with PRA > than 70%◦ average 74 months on the waiting list, ◦ 18 with transplant priority due to absence of HD vascular access.
All pts. have been treated with 3-9 monthly courses of 2 g/Kg of IVIg
Resistant cases: Rituximab and or PF addition
Increasing numbers of sensitized and prioritized patients on the WL
Absence of policies to prevent sensitization (transfusions) and problems with vascular access to dialysis
Absence of programs to evaluate the patient “transplantability” Absence of a national program for increase transplantability of
sensitized patients No reimbursement for various immunological studies and
desensitization strategies No reimbursement for techniques that could help in the
prevention, diagnose and correct treatment of AMR.
