A team headed by Deok Gie Kim from the Yonsei University College of Medicine, Republic of Korea, has conducted a study to demonstrate that patients subject to positive crossmatch kidney transplantation that has undergone desensitization show improved survival compared to those with compatible kidney transplantation.
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This desensitization is achieved by a protocol targeting donor-specific antibody (DSA); positive complement-dependent cytotoxicity (CDC) crossmatch (CDC+FC+) and positive flow cytometric crossmatch (CDC-FC+).
The team retrospectively analyzed 330 patients who underwent kidney transplants between 2011 and 2017. The team showed that similar graft and patient survival were achieved in both desensitization groups compared with those without.
Although positive crossmatch kidney transplantation is subject to high rejection rates relative to compatible kidney transplantation, the use of desensitization improves patient survival overall in positive crossmatch cohorts.
It is common knowledge that patients who received kidneys as a result of compatibility with human leukocyte antigen (HLA) antibody matching rather than positive crossmatch kidney transplantation (KT) demonstrate better outcomes.
Kidney transplantation is based on a patient’s sensitization; these patients possess positively acting antibodies against foreign tissue such as the transplanted organ.
A positive crossmatch will indicate a lack of suitability for kidney transplantation but owing to the long waitlist for patients on dialysis, patients must rely on positive crossmatch kidney transplantation for survival. As such, rigorous posttransplant immunosuppression must be implemented for patients who have no alternative.
Despite this, many patients undergo graft failure and mortality following positive crossmatch KT as opposed to compatible KT, hence only a few centers will employ the latter method.
Complement-dependent cytotoxicity methods
To overcome the high mortality risk associated with positive crossmatch KT, methods based on complement-dependent cytotoxicity (CDC) have been developed. These identify and characterize antibodies against the human leukocyte antigen (HLA).
Methods for identification include the single antigen assay and the C1q assay, which are used clinically. More sensitive methods flow cytometry crossmatch and single antigen assay have improved the quantification of antigens and underlined their importance in KT outcomes, specifically the single antigen assay (SAA).
This quantifies the strength of the antigen and is important in positive-cross match kidney transplantation where specific antibody titers are associated with the severity of the outcome.
The team investigated whether post-transplant outcomes of CDC positive (CDC+FC+) and FC positive patients (CDC-FC+) undergoing kidney transplantation were successful in the instance they were desensitized using an antibody targeted against a DSA.
To assess the success of the outcomes for these kidney transplantation types, these desensitized positive-crossmatch patients were compared with those patients characterized are negative-crossmatch candidates, compatible with kidney transplantation (CDC-FC-).
The team reviewed a population of 691 living donor kidney transplant recipients in Korea; of them, only 330 were subject to analysis and divided into 3 groups: CDC-FC-, CDC-FC+, and CDC + FC+. All subjects were assessed for donor-specific antigens before kidney transplantation via SSA.
The desensitization protocols employed involved the use of two immunoglobulins administered systematically; several doses were given to patients according to a desensitization schedule. The success of the desensitization protocol was assessed using SSA, C1q and cell-based crossmatch; a cut off median fluorescence intensity (MFI) ratio was assigned for the assays, although some patients successfully received kidney transplantation with MFIs greater than this.
Despite this, rejection occurred more frequently in these individuals. In general, however, both graft and patient survival rates seen in the desensitized positive cross-match patients were comparable to compatible kidney transplantation.
This result was also attributed to the use of treatment for acute rejection.
A major strength of this study was a detailed comparison of the complications that arise compared to previous studies. Immunosuppression is expected, but previous studies have not provided information regarding the complications.
The team headed by Kim was able to show that infections such as UTIs, CMVs, and bacteremia, occurred at aggressive prevalence in the positive crossmatch group compared to the compatible group.
The team concluded that despite the increased risk of infection, CDC + FC+ and CDC-FC+ groups demonstrated patient survival that rivaled that of compatible kidney transplantation patients.
Although the results were detailed, a limitation of the study was its retrospective single-center design, small population, and several events.
Also, the cohort was followed for 5 years only, so results cannot be extrapolated for use in long-term understanding. The team also notes that until specialized desensitization methods that are combined with thorough immunosuppressive methods are produced, higher rejection rates will continue to remain a challenge.
The authors appreciate Haejin Kim, Sensor Sohn, Sangmi Choi, and Wooyoung Chung at the Department of Laboratory Medicine, Yonsei University College of Medicine for their support in transplant immunology laboratory investigations,
Kim, D.G. et al. Transplant outcomes in positive complement-dependent cytotoxicity- versus flow cytometry-crossmatch kidney transplant recipients after successful desensitization: a retrospective study. BMC Nephrology. 2019. DOI: 10.1186/s12882-019-1625-2.