Prevention of hyperacute rejection by removal of antibodies to HLA immediately before renal transplantation

Higgins, Rob; Bevan, D. J.; Carey, Barbara; Lea, C K; Fallon, Michael J.; Bühler, Robert; Vaughan, R. W.; O’Donnell, Patrick; Snowden, S.; Bewick, M.; Hendry, Bruce

doi:10.1016/s0140-6736(96)03452-6

Cited by 111 publications

(90 citation statements)

References 18 publications

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“…ESRD patients who have high panel-reactive antibodies or donor-specific antibodies undergo desensitization, a complex medical regimen in which donor-specific antibodies are eliminated and production of new antibodies is inhibited to decrease immunologic risk and allow safer transplantation (52)(53)(54)(55)(56)(57)(58). Acute humoral rejection of renal allografts is caused by alloantibodies that cause kidney injury in the peritubular capillaries, resulting in endothelial damage, loss of capillary patency, ischemia, and proliferation of myofibroblasts.…”

Section: Kidney Transplantationmentioning

confidence: 99%

Principles of Separation

Williams

Balogun

2014

Clinical Journal of the American Society of Nephrology

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SummaryExtracorporeal "blood purification," mainly in the form of hemodialysis has been a major portion of the clinical activity of many nephrologists for the past 5 decades. A possibly older procedure, therapeutic plasma exchange, separates and then removes plasma as a method of removing pathogenic material from the patient. In contrast to hemodialysis, therapeutic plasma exchange preferentially removes biologic substances of high molecular weight such as autoantibodies or alloantibodies, antigen-antibody complexes, and Ig paraproteins. These molecular targets may be cleared through two alternative procedures: centrifugal separation and membrane separation. This review presents operational features of each procedure, with relevance to the nephrologist. Kinetics of removal of these plasma constituents are based on the principles of separation by the apheresis technique and by features specific to each molecular target, including their production and compartmentalization in the body. Molecular targets for common renal conditions requiring therapeutic plasma exchange are also discussed in detail.

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Section: Kidney Transplantationmentioning

confidence: 99%

Principles of Separation

Williams

Balogun

2014

Clinical Journal of the American Society of Nephrology

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“…Higgins et al used IA immediately before deceaseddonor kidney transplantation in 12 CDC or flow cytometry cross-match-positive patients (40). Nine patients had biopsies 20 minutes after removal of the vascular clamps and three showed glomerular thromboses but no other evidence of hyperacute rejection.…”

Section: Immumoadsorptionmentioning

confidence: 99%

Desensitization Protocols and Their Outcome

Marfo

Ling

et al. 2011

Clinical Journal of the American Society of Nephrology

235

184

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SummaryIn the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients.

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“…Moreover, creating a barrier to transplant access, preformed humoral alloreactivity often leads to unacceptably long waiting times without a suitable crossmatch-negative organ offer (1,2). (13)(14)(15). In this context, immunoadsorption (IA) may represent an attractive strategy for pronounced and selective alloantibody removal within the short time window between an organ offer and transplant surgery.…”

Section: Introductionmentioning

confidence: 99%

“…In this context, immunoadsorption (IA) may represent an attractive strategy for pronounced and selective alloantibody removal within the short time window between an organ offer and transplant surgery. In two earlier studies, IA with staphylococcal protein A columns has been examined as a strategy for rapid desensitization (13,14). Higgins et al (13) reported successful crossmatch conversion and prevention of hyperacute rejection by one or two extended pretransplant IA sessions.…”

Section: Introductionmentioning

confidence: 99%

Peritransplant Immunoadsorption for Positive Crossmatch Deceased Donor Kidney Transplantation

Bartel¹,

Wahrmann²,

Regele

et al. 2010

American Journal of Transplantation

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Various desensitization protocols were shown to enable successful living donor kidney transplantation across a positive complement-dependent cytotoxicity crossmatch (CDCXM). Positive crossmatch transplantation, however, is less well established for deceased donor transplantation. We report a cohort of 68 deceased donor renal allograft recipients who, on the basis of broad sensitization (lymphocytotoxic panel reactivity ≥40%), were subjected to a protocol of peritransplant immunoadsorption (IA). Treatment consisted of a single session of immediate pretransplant IA (protein A) followed by posttransplant IA and antilymphocyte antibody therapy. Twentyone patients had a positive CDCXM, which could be rendered negative by pretransplant apheresis. Solid phase HLA antibody detection revealed preformed donor-specific antibodies (DSA) in all 21 CDCXMpositive and in 30 CDCXM-negative recipients. At 5 years, overall graft survival, death-censored graft survival and patient survival were 63%, 76% and 87%, respectively, without any differences between CDCXM-positive, CDCXM-negative/DSA-positive and CDCXM-negative/DSA-negative recipients. Furthermore, groups did not differ regarding rates of antibodymediated rejection (24% vs. 30% vs. 24%, p = 0.84), cellular rejection (14% vs. 23% vs. 18%, p = 0.7) or allograft function (median 5-year serum creatinine: 1.3 vs. 1.8 vs. 1.7 mg/dL, p = 0.62). Our results suggest that peritransplant IA is an effective strategy for rapid desensitization in deceased donor transplantation.

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Prevention of hyperacute rejection by removal of antibodies to HLA immediately before renal transplantation

Cited by 111 publications

References 18 publications

Principles of Separation

Principles of Separation

Desensitization Protocols and Their Outcome

Peritransplant Immunoadsorption for Positive Crossmatch Deceased Donor Kidney Transplantation

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