ABO incompatible renal transplants: Good or bad?

Table 1 Combination of blood type and compatibility

		Donor
		A	B	O	AB
Recipient	A	-	+	-	+
	B	+	-	-	+
	O	+	+	-	+
	AB	-	-	-	-

+: ABO incompatible transplantation; -: ABO compatible transplantation.

Table 2 Historical clinical reports in ABO incompatible kidney transplantation

Ref.	Type of study	Study population	ABOi population	Desensitization	Outcome
Hume et al[18]	Observational	9	1	No treatment	Graft nephrectomy day 17
Starzl et al[19]	Observational	3	2	SPx (1 case)	Graft survival 74 d (1 case), patient death day 24 (1 case)
Sheil et al[20]	Observational	2	2	No treatment	Graft nephrectomy day 14
Alexandre et al[11]	Observational	23	23	PE/SPx	2-yr graft survival: 88% (related donor), 50% (unrelated donor)
Ota et al[21]	Observational, comparative	51	51	DFPP and/or IAs/SPx	2-yr graft survival: 87% vs 84.6% vs 50% ( A- vs B- vs ABO-incompatible)
Tanabe et al[22]	Observational, comparative	433	67	DFPP and IAs/SPx	8-yr graft survival: 73% vs 80 % (ABOi vs ABOc)
Ishida et al[23]	Observational	93	93	DFPP/SPx	5-yr graft survival: 73%
Ohta et al[24]	Observational, pediatric	10	10	DFPP or PE or IAs/SPx	5.4-yr graft survival: 100%
Shishido et al[25]	Observational, pediatric	16	16	PE and IAs/SPx	5-yr graft survival: 85%
Takahashi et al[2]	Observational, comparative	1496	441	DFPP or PE or IAs/SPx	9-yr graft survival: 59% vs 57% (ABOi vs ABOc)
Shimmura et al[26]	Observational, comparative	167	167	DFPP and/or IAs/SPx	5-yr graft survival: 74.3% vs 78.5% ( CYA with AZ or MZ vs TAC or MMF)
Futagawa et al[27]	Observational, comparative	37803	191	NA	5-yr graft survival: 66.2% vs 79.5% (ABOi vs ABOc)
Ishida et al[28]	Observational, comparative	222	222	DFPP/SPx	5-yr graft survival: 73% vs 90% ( CYA with AZ vs TAC with MMF)
Tyden et al[29]	Observational, comparative	334	60	IAs/RIT/IVIG	Graft survival: ABOi 97% (1.5-yr) vs ABOc 95% (1.8-yr)
Galliford et al[30]	Observational	10	10	PE/RIT/IVIG	1-yr graft survival: 100%
Genberg et al[31]	Observational, comparative	45	15	IAs/RIT/IVIG	Graft survival: ABOi 86.7% (3.4-yr) vs ABOc 86.7% (4.0-yr)
Oettl et al[32]	Observational	10	10	IAs/RIT/IVIG	1.3-yr graft survival: 100%
Toki et al[33]	Observational, comparative	57	57	DFPP/SPx	8-yr graft survival: 49% vs 95% (AAMR vs non-AAMR)
Wilpert et al[34]	Observational, comparative	83	40	IAs/RIT/IVIG	Graft survival: ABOi 100% (3.3-yr) vs ABOc 93% (1.5-yr)
Tyden et al[1]	Observational, comparative, pediatric	38	10	IAs/RIT/IVIG	Graft loss within 3 years: ABOi 1 case, ABOc 2 cases
Flint et al[35]	Observational, comparative	89	37	PE/IVIG	1-yr graft survival: 100% (ABOi vs ABOc)
Fichinoue et al[36]	Observational, comparative	393	113	DFPP or PE/SPx or RIT	5-yr graft survival: 88.4% vs 90.3% vs 100% (ABOc vs ABOi-SPx vs ABOi-RIT)
Habicht et al[37]	Observational, comparative	68	21	IAs/RIT/IVIG	1-yr graft survival : 100% (ABOi vs ABOc)
Lipshutz et al[38]	Observational	18	18	PE/RIT/IVIG	1-yr graft survival: 94.4%
Shirakawa et al[39]	Observational, comparative	74	74	DFPP/RIT	1-yr graft survival: 95.7% vs 98.% ( RIT 500mg vs RIT 200 mg)
Shishido et al[3]	Observational, comparative, pediatric	323	52	PE/SPx or RIT	15-yr graft survival: 86% vs 78% (ABOi vs ABOc)
Montgomery et al[4]	Observational, comparative	78193	738	NA	10-yr cumulative incidence of graft loss: 27.1% vs 23.9% (ABOi vs ABOc)
Morath et al[40]	Observational, comparative	19	19	IAs or IAns/RIT/IVIG	1-yr graft survival: 100% (IAs vs IAns)
Uchida et al[41]	Observational	25	25	DFPP or PE/SPx or RIT	4.5-yr graft survival: 100%
Ashimine et al[42]	Observational, comparative	320	92	DFPP/SPx or RIT or none	5-yr graft survival: 87% vs 97.7% (ABOi vs ABOc)

ABOi: ABO incompatible; SPx: Splenectomy; PE: Plasma exchange; DFPP: Double-filtration plasmapheresis; IAs: Antigen-specific immunoadsorption; ABOc: ABO compatible; CYA: Cyclosporine; AZ: Azathioprine; MZ: Mizoribine; TAC: Tacrolimus; MMF: Mycophenolate mofetil; NA: Not available; RIT: Rituximab; IVIG: Intravenous immunoglobulin; AAMR: Acute antibody-mediated rejection; IAns: Non-antigen-specific immunoadsorption.

Table 3 Current protocols for ABO incompatible kidney transplantation

Author	Country,year	Rituximab dose	Pretransplant IS	Antibody depletion	IVIG	Target titer at the time of transplantation	Induction IS	Maintenance IS	Posttransplant antibody depletion
Adult recipients
Rituximab protocol
Saito et al[53]	Japan,2006	375 mg/m2 (twice) at -14 and -1 d	MMF/MP at -1 mo	DFPP or PE	-	< 1:16	BAS (20 mg at 0and 4 d)	CYA/MMF/MP	-
Tyden et al[54]	Sweden, 2006	375 mg/m2 (once) at -1 mo	TAC/ MMF/Pred at -13 d	IAs	0.5 g/kg after last IAs	< 1:8	-	TAC/MMF/Pred	IAs, 3 times
Chikaraishi et al[55]	Japan,2008	100 mg/m2 (twice) at -8 and -1 d	MMF/MP at -14 d, TAC at -3 d	DFPP and PE	-	< 1:8	BAS (20 mg at 0and 4 d)	TAC/MMF/MP	-
Galliford et al[30]	United Kingdom, 2008	1000 mg (twice) at first day of PE and at the operative day	TAC/MMF at -14 d	PE	0.1 g/kg after each PE	< 1:4	DAC (2 mg/kg at 0 and 14 d)	TAC/MMF/Pred	PE at 1 and 3 d
Genberg et al[31]	Sweden, 2008	375 mg/m2 (once) at -1 mo	TAC/MMF/Pred at -10 d	IAs	0.5 g/kg at -1 d	< 1:8	-	TAC/MMF/Pred	IAs, 3 times
Oettl et al[32]	Switzerland, 2009	375 mg/m2 (once) at -1 mo	TAC/MMF /Pred at -14 d	IAs	0.5 g/kg after lastIAs	< 1:8	BAS (20 mg at 0and 4 d)	TAC/MMF/Pred	IAs or PE (not routinely)
Sivakumaran et al[78]	United States, 2009	375 mg/m2 (once) at -3 wk	MMF at -1 mo	PE	2 g/kg after last PE	NA	ALE (1 mg/kg at 0 and 14 d)	TAC/MMF/Pred	-
Wilpert et al[34]	Germany, 2010	375 mg/m2 (once) at -1 mo	TAC/MMF or MPS/Pred at -7 d	IAs	0.5 g/kgat -1 to-5 d	< 1:4	BAS (20 mg at 0and 4 d)	TAC/MMF/Pred	IAs (not routinely)
Fuchinoue et al[36]	Japan,2011	100-1000 mg, 1-3 times	CYA or TAC/MMF at -2 d	DFPP or PE	-	< 1:16	BAS (20 mg at 0and 4 d)	CYA or TAC/MMF/steroid	-
Habicht et al[37]	Germany, 2011	375 mg/m2 (once) at -1 mo	TAC/MMF/Pred at -1 mo	IAs	30 g at -1to -2 d	< 1:8	-	TAC/MMF/MP	IAs (not routinely)
Lipshutz et al[38]	United States, 2011	375 mg/m2 (once) at -1 mo	TAC/MMF at the first day of PE	PE	10 g after each PE	< 1:8	ATG (1.5 mg/kgfor 4 d)	TAC/MMF/Pred	PE (not routinely)
Shirakawa et al[39]	Japan, 2011	500 or 200 mg/m2 (once), at -5 to -7 d	TAC/MMF/MP at -7 d	DFPP	-	< 1:32	BAS (20 mg at 0and 4 d)	TAC/MMF/MP	-
Morath et al[40]	Germany, 2012	375 mg/m2 (once) at -1 mo	TAC/MMF/MP at the first day of IAs	IAs	0.5 g/kg after lastIAs	< 1:16	BAS (20 mg at 0and 4 d)	TAC/MMF/MP	IAs or PE (not routinely)
Uchida et al[41]	Japan,2012	150 mg/m2 (twice) at -14 and 0 d	MMF/MP at -1 Mo, CYA or TAC at -3 d	DFPP or PE	-	< 1:16	BAS (20 mg at 0and 4 d)	CYA or TAC/MMF/MP	-
Rituximab-free protocol
Montgomery et al[43]	United States,2009	-	TAC/MMF at the first day of PE	PE	0.1 g/kg after each PE	< 1:16	DAC (2 mg/kg initial dose, 1 mg/kg every 2 wk for total 5 doses)	TAC/MMF/Pred	PE, at least twice (with IVIG 0.1 g/kg)
Flint et al[35]	Australia, 2011	-	MMF at -10 to -14 d	PE	0.1 g/kg after each PE	< 1:8	BAS (20 mg at 0 and 4 d)	TAC/MMF/Pred	PE (not routinely)
Ashimine et al[42]	Japan,2013	-	MMF at -14 d	DFPP	-	< 1:8	BAS (20 mg at 0 and 4 d)	CYA or TAC/MMF/Pred	-
Pediatric recipients
Genberg et al[31]	Sweden, 2008	375 mg/m2 (once) at -1 mo	TAC/MMF/Pred at -10 d	IAs	0.5 g/kg at -1 d	< 1:8	-	TAC/MMF/Pred	IAs, 3 times
Tyden et al[1]	Sweden, 2011[1]	375 mg/m2 (once) at -1 mo	TAC/MMF/Pred at -13 d	IAs	0.5 g/kg after lastIAs	< 1:8	-	TAC/MMF/ Pred	IAs, 3 times

IS: Immunosuppression; IVIG: Intravenous immunoglobulin; MMF: Mycophenolate mofetil; MP: Methylprednisolone; DFPP: Double-filtration plasmapheresis; PE: Plasma exchange; BAS: Basiliximab; CYA: Cyclosporine; TAC: Tacrolimus; Pred: Prednisolone; IAs: Antigen-specific immunoadsorption; DAC: Daclizumab; NA: Not available; ALE: Alemtuzamab; MPS: Mycophenolate sodium; ATG: Antithymocyte globlin.

Table 4 Pro and cons for ABO incompatible kidney transplantation

Pro ABOi-KT

Reducing waiting list and time

Expanding living donor pool

Improvement of patient's prognosis

Excellent graft survival (comparable with ABOc-KT)

Contra ABOi-KT

Comparative high immunological risk

Higher incidence of acute AMR

Intensified immunosuppression

Antibody depletion therapy

Increasing expenditure

Higher incidence of viral infection

ABOi-KT: ABO incompatible kidney transplantation; ABOc-KT: ABO compatible kidney transplantation; AMR: antibody-mediated rejection.