Current Perspectives in ABO-Incompatible Kidney Transplant

Figures & data

Figure 1 The possible pathogenetic mechanism of different B cell response in patients receiving AB0i kidney transplant. Thymus-independent antigens may cause the switch from B1 cells producing low avidity IgM to B2 cells able to produce high levels of complement-fixing IgG1, which can predispose to rejection.

Table 1 Main Papers Comparing the Outcome of Patients Who Underwent ABOi Kidney Transplant with Patients Who Received ABOc Kidney Transplant

Study	Population	Anti-A/B Antibodies Median Initial Titer	Desensitization Strategy	Target Anti-A/B Pre-Operative Titer	Post-Operative Target	Outcomes	Adverse Events
Genberg et al (2008)^Citation49	15 adult AB0i vs 30 adult AB0c 5 pediatric AB0i vs 18 pediatric AB0c (September 2001- December 2005)	1:32 (adults) 1:16 (pediatrics)	-Repeated antigen-specific IA + -RTX 375mg/m^2 on day −30 and immunosuppressive therapy on day −10 -IVIG 0.5 g/kg on day −1 and for five days after transplant	NR	−3 IA sessions after transplant	-No differences in graft and patient’s survival -No differences in rejection episodes	-No differences in infective complications
Barnett et al (2014)^Citation10	62 AB0i vs 167 AB0c KT (July 2005- November 2011)	NR	-Repeated antigen-specific IA (if titer> 1:64) or DFPP (if titer 1:16–1:64) + -RTX 375mg/m^2 on day −30 and immunosuppressive therapy -IVIG 0.5 g/kg pre and post- transplant (until 2009)	NR	- On demand post- transplant antibody removal	-No differences in graft survival -No differences in rejection episodes	− 3 deaths in AB0i group due to Pneumocystis pneumonia - 1 death in AB0i group due to sepsis
Okumi et al (2015)^Citation50	247 AB0i vs 785 AB0c KT (January 1989 – December 2013)	NR	-Three or four sessions of DFPP before transplantation + -Splenectomy (from 1989 to 2004) or RTX 200 mg on day −7 (after 2004)	< 1:32	-No prophylactic postoperative DFPP or IGIV to maintain low titers	-Significant difference in graft survival until 2004 (68.9% for AB0i and 78.1% for AB0c KT, p=0.026) -No differences in graft survival after 2005 -No differences in patient survival	- Higher rates of CMV and adenovirus infections were observed in AB0i KT recipients before 2004 -No differences in infective complications after 2005
Becker et al (2015)^Citation48	34 AB0i vs 68 AB0c KT (August 2005- December 2013)	1:64	-Nonantigen-specific IA (number of sessions depending on initial titer, median = 7) -PE (until 2012 only additional PE to reach the target titer; from 2012 at least one pre -transplant treatment, median = 2) + -RTX 375mg/m^2 2–4 weeks before surgery and immunosuppressive therapy started with IA -IVIG 0.5 g/kg in 7 patients	≤1:8	−21 pts had PE to maintain ≤1:16 in the first week and ≤ 1:32 in the second week after surgery.	-No differences in graft survival or rejection episodes. -Statistically significant difference in patient survival (2 deaths in AB0i group vs 0 deaths in AB0c group, p=0.05)	-No differences in surgical complications. -Higher risk of BKV nephropathy (p=0.01) and of colonization of multidrug-resistant bacteria (p=0.02) in AB0i group.
Speer et al (2019)^Citation47	48 AB0i vs 96 AB0c KT (August 2005-August 2018)	1:32	-Semiselective IA (number of sessions depending on initial titer, median = 6) -PE (at least one treatment to reach target preoperative titer, median = 2) + RTX 375mg/m^2 2–4 weeks before surgery and immunosuppressive therapy started with IA	≤1:8	−50% pts had IA or PE to maintain titers ≤1:16 in the first week and ≤ 1:32 in the second week after surgery.	-No differences in graft and patient survival or rejection episodes.	-AB0i more postoperative bleeding and more complicated UTI, severe pneumonia, CVC-related infections by MDR bacteria. -No differences in BKV or CMV infections.

Abbreviations: AB0i KT, AB0 incompatible kidney transplant; AB0c KT, AB0 compatible kidney transplant; IA, immunoadsorption; PE, plasma exchange; DFPP, double-filtration plasmapheresis; RTX, rituximab; IVIG, intravenous immunoglobulins; UTI, urinary tract infections; CMV, cytomegalovirus.

Figure 2 The desensitization strategy performed in ABOi kidney transplant patients. A single infusion of rituximab 375 mg/mq is administrated four weeks before kidney transplant. Two weeks before kidney transplant, patient starts oral immunosuppressive therapy (tacrolimus and mycophenolate mofetil). A variable number of immunoadsorption and/or plasma exchange (PEX) sessions is performed before kidney transplant, until a titer < or = at 1:8 is achieved. The isohemagglutinin titer is measured every day after ABOi kidney transplant and further PEX sessions are performed on demand.

Genberg H, Kumlien G, Wennberg L, et al. ABO-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab: a 3-year follow-up. Transplantation. 2008;85(12):1745–1754. doi:10.1097/TP.0b013e3181726849

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Barnett AN, Manook M, Nagendran M, et al. Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation. Transpl Int. 2014;27(2):187–196. doi:10.1111/tri.12234

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Okumi M, Toki D, Nozaki T, et al. ABO-incompatible living kidney transplants: evolution of outcomes and immunosuppressive management. Am J Transplant. 2016;16(3):886–896. doi:10.1111/ajt.13502

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Becker LE, Siebert D, Süsal C, et al. Outcomes following ABO-incompatible kidney transplantation performed after desensitization by nonantigen-specific immunoadsorption. Transplantation. 2015;99(11):2364–2371. doi:10.1097/TP.0000000000000753

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Speer C, Kälble F, Nusshag C, et al. Outcomes and complications following ABO-incompatible kidney transplantation performed after desensitization by semi-selective immunoadsorption - a retrospective study. Transpl Int. 2019;32(12):1286–1296. doi:10.1111/tri.13482

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