ABO incompatible kidney ABO incompatible kidney transplantation transplantation Ulla B. Berg, Division of Pediatrics Ulla B. Berg, Division of Pediatrics The presentation is based on slides from Gunnar Tydén The presentation is based on slides from Gunnar Tydén and Helena Genberg, Division of Transplantation and Helena Genberg, Division of Transplantation Surgery, Surgery, Dept. of Clinical Science, Intervention and Technology, Dept. of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Karolinska University Hospital Huddinge, Stockholm, Sweden Sweden
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ABO incompatible kidney transplantation Ulla B. Berg, Division of Pediatrics The presentation is based on slides from Gunnar Tydén and Helena Genberg,
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Ulla B. Berg, Division of PediatricsUlla B. Berg, Division of Pediatrics
The presentation is based on slides from Gunnar Tydén and Helena The presentation is based on slides from Gunnar Tydén and Helena Genberg, Division of Transplantation Surgery,Genberg, Division of Transplantation Surgery,
Dept. of Clinical Science, Intervention and Technology, Dept. of Clinical Science, Intervention and Technology,
Karolinska University Hospital Huddinge, Stockholm, SwedenKarolinska University Hospital Huddinge, Stockholm, Sweden
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Reasons to increase the number of Reasons to increase the number of living donor renal transplantsliving donor renal transplants
The increasing discrepancy between the The increasing discrepancy between the number of available deceased donor organs number of available deceased donor organs and the number of patients on the waiting listand the number of patients on the waiting list
The superior graft and patient survival rates The superior graft and patient survival rates obtained with living donor transplantsobtained with living donor transplants
0102030405060708090
100
0 2 4 6 8 10Years after transplantation
Gra
ft s
urv
iva
l, %
LD (n=363)DD (n=626)
0102030405060708090
100
0 2 4 6 8 10Years after transplantation
Gra
ft s
urv
iva
l, %
LD (n=363)DD (n=626)
Kidney transplantations in Stockholm Kidney transplantations in Stockholm 1990-20021990-2002
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Kidney transplantations in Stockholm Kidney transplantations in Stockholm 1990-20021990-2002
10 year survival10 year survival
Graft (%)Graft (%) Patient (%)Patient (%)
Living donorLiving donor 7070 8585
Deceased donorDeceased donor 4040 5555
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Evolution of living donor programmesEvolution of living donor programmes
Parents, HLA- identical or Parents, HLA- identical or haploidentical siblingshaploidentical siblings
The likelihood that two The likelihood that two unrelated individuals are:unrelated individuals are:- identical is 37.5%- identical is 37.5%- compatible is 26.75%- compatible is 26.75%- incompatible is 35.75%- incompatible is 35.75%
The likelihood that two The likelihood that two unrelated individuals are:unrelated individuals are:- identical is 37.5%- identical is 37.5%- compatible is 26.75%- compatible is 26.75%- incompatible is 35.75%- incompatible is 35.75%
Immunohistochemistry for detection of Immunohistochemistry for detection of A antigen in a blood group AA antigen in a blood group A11 kidney kidney
8
A1 A2A2
Breimer et al Transplantation 82: 479, 2006
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Previous experience in APrevious experience in A11 and B and B
Overall very poor resultsOverall very poor results
Therefore ABO incompatibility was considered an absolute Therefore ABO incompatibility was considered an absolute
contraindication to kidney transplantationcontraindication to kidney transplantation
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Previous experience in APrevious experience in A2 2 AB0-incompatible AB0-incompatible
kidney transplantationkidney transplantation Year of publication:Year of publication: 1987: Gothenburg, Sweden (Breimer, Rydberg et al) (n=23)1987: Gothenburg, Sweden (Breimer, Rydberg et al) (n=23) 1987: London, UK (Welsh et al.) (n=16)1987: London, UK (Welsh et al.) (n=16) 1998: Kansas, USA (Nelson et al.) (n=50)1998: Kansas, USA (Nelson et al.) (n=50) 1999: Portland, Oregon, USA (Alkhunaizi et al.) (n=15)1999: Portland, Oregon, USA (Alkhunaizi et al.) (n=15) 2001: Salt Lake City, Utah, USA (Sorensen et al.) (n=15)2001: Salt Lake City, Utah, USA (Sorensen et al.) (n=15)
Between 1974-1988 23 DD kidney Between 1974-1988 23 DD kidney transplantations across the Atransplantations across the A22 barrier were barrier were
performed, using regular immunosuppression performed, using regular immunosuppression
1-year graft survival was approx. 55%.1-year graft survival was approx. 55%.
Between 1974-1988 23 DD kidney Between 1974-1988 23 DD kidney transplantations across the Atransplantations across the A22 barrier were barrier were
performed, using regular immunosuppression performed, using regular immunosuppression
1-year graft survival was approx. 55%.1-year graft survival was approx. 55%.
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Previous experience in APrevious experience in A11 and B and B
AB0-incompatible kidney transplantationAB0-incompatible kidney transplantationYear of first transplantation:Year of first transplantation:
1955: Boston, Massachussets, USA, (Hume et al.)1955: Boston, Massachussets, USA, (Hume et al.)
1960: Murray1960: Murray
1964 Starzl 1964 Starzl
1981: Portsmouth, UK (Slapak et al.)1981: Portsmouth, UK (Slapak et al.)
1982: Brussels, Belgium (Alexandre et al.) (n=26)1982: Brussels, Belgium (Alexandre et al.) (n=26)
1989: Japan (Tanabe et al.)1989: Japan (Tanabe et al.)
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Present experiences in a series of 26 ABO-incompatible Present experiences in a series of 26 ABO-incompatible living donor renal allograftsliving donor renal allografts
Alexandre GPJ, Squifflet JP et alAlexandre GPJ, Squifflet JP et alTranplantation Proceedings vol XIX no 6 1987 pp 4538-4542Tranplantation Proceedings vol XIX no 6 1987 pp 4538-4542
donor specific platelet transfusiondonor specific platelet transfusion
plasmapheresis plasmapheresis
splenectomysplenectomy
cyclosporin A, prednisolone, azathioprine cyclosporin A, prednisolone, azathioprine
polyclonal Abs (ALG or ATG)polyclonal Abs (ALG or ATG)
substance A or B substance A or B
3 not splenectomized recipients hyperacutely rejected 3 not splenectomized recipients hyperacutely rejected their grafts during the first postoperative week their grafts during the first postoperative week
Plasma separation
Replacement fluid(albumin, plasma)
Plasma discarded
Plasma exchangePlasma exchange
blood cells
plasma
Disadvantages:Disadvantages:
LimitedLimited efficacy due to restrictions to the plasma volume processed. efficacy due to restrictions to the plasma volume processed.
All plasma components are reduced including coagulation factors.All plasma components are reduced including coagulation factors.
Fluid replacement is necessary.Fluid replacement is necessary.
Disadvantages:Disadvantages:
LimitedLimited efficacy due to restrictions to the plasma volume processed. efficacy due to restrictions to the plasma volume processed.
All plasma components are reduced including coagulation factors.All plasma components are reduced including coagulation factors.
Fluid replacement is necessary.Fluid replacement is necessary.
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Lessons learned from ABO-incompatible living donor Lessons learned from ABO-incompatible living donor kidney transplantation: 20 years later.kidney transplantation: 20 years later.
Squifflet JP, De Meyer M, Malaise J, Latinne D, Pirson Y, Alexandre GPSquifflet JP, De Meyer M, Malaise J, Latinne D, Pirson Y, Alexandre GP. . Exp Clin Transplant. 2004 2:208-13.Exp Clin Transplant. 2004 2:208-13.
– ““Pretransplant therapies included Pretransplant therapies included platelets donor platelets donor transfusiontransfusion, 2 to 5 , 2 to 5 plasmapheresisplasmapheresis sessions, sessions, cyclosporin cyclosporin A with or without azathioprineA with or without azathioprine along with along with polyclonal Abspolyclonal Abs and and splenectomy splenectomy at the time of transplantation. After the at the time of transplantation. After the last plasmapheresis session, when the level of 1/4 (ABO last plasmapheresis session, when the level of 1/4 (ABO antibodies) was reached, all recipients received antibodies) was reached, all recipients received 5 mL of 5 mL of substance A or B.” substance A or B.”
39 ABO incompatible living donor grafts39 ABO incompatible living donor grafts
Exp Clin Transplant. 2004 2:208-13.
15Exp Clin Transplant. 2004 2:208-13
<15 y
>15 y
78%
59%
39 ABOi tx
16
39 ABOi tx Rec. <15 y
N=38
N=8
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RRemoval ofemoval of A Antinti-A/B -A/B antibodies antibodies
AB0 -incompatible kidney transplantation AB0 -incompatible kidney transplantation using antigen-specific immunoadsorption and using antigen-specific immunoadsorption and rituximab: a 3-year follow-uprituximab: a 3-year follow-up
Genberg H et al Transplantation 85:1745-1754, 2008
ABO-incomp.ABO-incomp. ABO-compABO-comp..
AdultsAdults 1515 3030
Mean rec.ageMean rec.age 35.135.1 42.442.4
Mean don.ageMean don.age 52.852.8 49.049.0
ChildrenChildren 5 5 1818
Mean rec.ageMean rec.age 8.6 8.6 7.8 7.8
Mean don.ageMean don.age 42.542.5 42.842.8
Grafted during the same time periodGrafted during the same time period
In adults: the same basic immunosuppression In adults: the same basic immunosuppression
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Rejection episodes in adult kidney recipients Rejection episodes in adult kidney recipients
One patient died with functioning graft after 4 months
One graft was lost in non compliance after 22 months
All the remaining 58 grafts have normal function at a
follow up of 1 - 60 months
Tydén G et al Transplantation 2007 83:1153-1155
The Stockholm/Freiburg/Uppsala experience with The Stockholm/Freiburg/Uppsala experience with ABO incompatible transplantationsABO incompatible transplantations
43Tydén G et al Transplantation 2007 83:1153-1155
NN ActualActual graftgraft ActualActual Follow-upFollow-upsurvivalsurvival S-creatinineS-creatinine monthsmonths
The Stockholm/Freiburg/Uppsala experience with The Stockholm/Freiburg/Uppsala experience with LD kidney transplantations performed 2002-2006LD kidney transplantations performed 2002-2006
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nn Ab-titreAb-titre Ab-titreAb-titre Cancelled txCancelled tx Mean no Mean no preop.preop.
The Stockholm/Freiburg/Uppsala experience with The Stockholm/Freiburg/Uppsala experience with ABO incompatible transplantationsABO incompatible transplantations