Transplant outcomes in positive complement-dependent cytotoxicity- versus flow cytometry-crossmatch kidney transplant recipients after successful desensitization: a retrospective study

Kim, Deok Gie; Lee, Juhan; Park, Younhee; Kim, Myoung Soo; Jeong, Hyeon Joo; Kim, Soon Il; Kim, Yu Seun; Kim, Beom Seok; Huh, Kyu Ha

doi:10.1186/s12882-019-1625-2

Cited by 9 publications

(3 citation statements)

References 33 publications

(31 reference statements)

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“…A report by Kim ( 66 ) compared 56 HLAi (positive T cell flow cytometric crossmatches were excluded) with 274 compatible transplants, providing data on infectious complications, which may help in considering the risk. Urinary tract infections (41% vs. 7.7%), cytomegalovirus viraemia (54% vs. 14%) and pneumocystis jiroveci pneumonia (PJP) (5% vs. 0%) were all significantly higher in the HLAi group ( p < 0.001).…”

Section: Outcomes After Hla Incompatible Transplantationmentioning

confidence: 99%

European Guideline for the Management of Kidney Transplant Patients With HLA Antibodies: By the European Society for Organ Transplantation Working Group

Mamode

Bestard

Claas³

et al. 2022

Transpl Int

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This guideline, from a European Society of Organ Transplantation (ESOT) working group, concerns the management of kidney transplant patients with HLA antibodies. Sensitization should be defined using a virtual parameter such as calculated Reaction Frequency (cRF), which assesses HLA antibodies derived from the actual organ donor population. Highly sensitized patients should be prioritized in kidney allocation schemes and linking allocation schemes may increase opportunities. The use of the ENGAGE 5 ((Bestard et al., Transpl Int, 2021, 34: 1005–1018) system and online calculators for assessing risk is recommended. The Eurotransplant Acceptable Mismatch program should be extended. If strategies for finding a compatible kidney are very unlikely to yield a transplant, desensitization may be considered and should be performed with plasma exchange or immunoadsorption, supplemented with IViG and/or anti-CD20 antibody. Newer therapies, such as imlifidase, may offer alternatives. Few studies compare HLA incompatible transplantation with remaining on the waiting list, and comparisons of morbidity or quality of life do not exist. Kidney paired exchange programs (KEP) should be more widely used and should include unspecified and deceased donors, as well as compatible living donor pairs. The use of a KEP is preferred to desensitization, but highly sensitized patients should not be left on a KEP list indefinitely if the option of a direct incompatible transplant exists.

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Section: Outcomes After Hla Incompatible Transplantationmentioning

confidence: 99%

European Guideline for the Management of Kidney Transplant Patients With HLA Antibodies: By the European Society for Organ Transplantation Working Group

Mamode

Bestard

Claas³

et al. 2022

Transpl Int

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“…Although it has been well-established that pretransplant DSA is associated with increased risk of rejection and inferior graft survival outcomes, limited data exist on the risk of infections in this population. In one study comparing the outcomes among CDC flow crossmatch positive recipients, who had undergone desensitization before transplant, Kim et al 22 noted an increased incidence of urinary tract infection, Pneumocystis jirovecii pneumonia, and CMV viremia compared with both CDC and flow crossmatch negative recipients. In another study from our institution among 254 kidney transplant recipients, we found pretransplant DSA with MFI more than 500 was associated with an increased risk for the development of BK or CMV infection in the univariate analysis.…”

Section: Infectious Complicationsmentioning

confidence: 99%

Impact of low‐level pretransplant donor‐specific antibodies on outcomes after kidney transplantation

Parajuli

Bath

Hidalgo

et al. 2021

Immunity Inflam & Disease

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Background: The effect of low-level pretransplant donor-specific antibody (DSA) on kidney transplant outcomes is not well described. The goal of this study was to compare outcomes among patients of varying immunologic risk, based on the level of pretransplant DSA. Methods:We retrospectively reviewed all adult kidney transplant recipients who had undergone a transplant at our center between January 2013 and May 2017. Patients were grouped as negative DSA (mean fluorescence intensity, [MFI SUM < 100]), low-level DSA (MFI SUM 100-1000), and positive DSA (MFI SUM > 1000). Rejection, infection, graft, and patient survival were outcomes measured. Results: Of 952 patients, 82.1% had negative DSA, 10.7% had low-level DSA, and 7.1% had positive DSA. The positive DSA group had the highest rate of antibody-mediated rejection (10.3%), followed by low-level DSA (7.8%) and the negative DSA group (4.5%) (p = .034). The rate of BK viremia was highest in the positive DSA group (39.7%), followed by the low-level group (30.4%) and the negative DSA group (25.6%), (p = .025). None of the other outcomes, including graft or patient survival, were different between the groups. Conclusion: While low-level DSA should not prevent proceeding with kidney transplantation, it should not be ignored. Future studies are needed to investigate the long-term effects of varying levels of pre-transplant DSA on outcomes.

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“…[5][6][7] In transplantation, the CDC mechanism of RTX action can cause confusing false-positive results in CDC crossmatch tests. [8][9][10][11] In contrast, obinutuzumab (OBZ), a more recent monoclonal antibody against B-lymphocytes, induces more ADCC, antibody-dependent phagocytosis (ADP), and direct ADC, but much less CDC. 4,8,[11][12][13] Overall, B-cell depletion with OBZ and antibody half-life 13 are greater than with RTX, which translates into superior efficacy when treating some types of lymphoma and lupus nephritis.…”

Section: Introductionmentioning

confidence: 99%

Obinutuzumab in Kidney Transplantation: Effect on B-cell Counts and Crossmatch Tests

et al. 2021

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Background. Resistance to the action of rituximab (RTX) has been documented in several diseases. More recently, obinutuzumab (OBZ) has shown promise where RTX has failed in oncology and lupus nephritis. Unlike RTX, OBZ is a weak activator of complement, which may avoid the false-positive complement-dependent cytotoxicity (CDC) crossmatch tests after RTX infusions. Methods. The aim of this study was to explore the effect of OBZ on B-cell depletion in kidney-transplant candidates and its impact on crossmatch test results. We included 12 patients, who were either highly sensitized kidney-transplant candidates or kidney-transplant recipients presenting with antibody-mediated rejection. Six received OBZ, and 6 received RTX. CD-19 counts, flow cytometry, and CDC crossmatch tests were run immediately before and at 2 wk after drug infusion. Results. OBZ reduced CD-19 counts: median reduction was 98%. B-cell CDC crossmatch test results became positive following RTX infusion but were not affected by OBZ infusion. Conclusions. OBZ effectively depleted B-cell counts in sensitized kidney-transplant candidates and, unlike RTX, had no effect on CDC crossmatch results.

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Transplant outcomes in positive complement-dependent cytotoxicity- versus flow cytometry-crossmatch kidney transplant recipients after successful desensitization: a retrospective study

Cited by 9 publications

References 33 publications

European Guideline for the Management of Kidney Transplant Patients With HLA Antibodies: By the European Society for Organ Transplantation Working Group

European Guideline for the Management of Kidney Transplant Patients With HLA Antibodies: By the European Society for Organ Transplantation Working Group

Impact of low‐level pretransplant donor‐specific antibodies on outcomes after kidney transplantation

Obinutuzumab in Kidney Transplantation: Effect on B-cell Counts and Crossmatch Tests

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