Positive Luminex and negative flow cytometry in kidney transplantation: a systematic review and meta-analysis

Abstract

The presence of pre-formed donor-specific antibodies (DSAs) in kidney transplantation is associated with worse overall outcomes compared with DSA-negative transplantation. A positive complement-dependant cytotoxic crossmatch presents a high immunological risk, while a negative flow cytometry crossmatch is at the lower end of the risk spectrum. Yet, the presence of low-level DSA detected by Luminex alone, that is, positive Luminex and negative flow (PLNF) cytometry crossmatch lacks robust scientific exploration. In this systematic review and pooled analysis, we investigate the glomerular filtration rate, acute rejection (AR), graft survival and patient survival of PLNF transplants compared with DSA-negative transplants. Our analysis identified seven retrospective studies consisting of 429 PLNF transplants and 10 677 DSA-negative transplants. Pooled analysis identified no significant difference in the incidence of AR at 1 year [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.90–2.02, Z = 1.46, P = 0.14, I2 = 0%], graft failure at 1 year (RR = 1.66, 95% CI 0.94–2.94, Z = 1.75, P = 0.08, I2 = 23%), graft failure at 5 years (RR = 1.29, 95% CI 0.90–1.87, Z = 1.38, P = 0.17, I2 = 0%), patient mortality at 1 year (RR = 0.89, 95% CI 0.31–2.56, Z = 0.22, P = 0.82, I2 = 0%) and patient mortality at 5 years (RR = 1.76, 95% CI 0.48–6.48, Z = 0.85, P = 0.39, I2 = 61%). Pooled analysis of graft function was not possible due to insufficient data. Current evidence suggests that low-level DSA detected by Luminex alone does not pose significant risk at least in the short–medium term. Considering the shortage of kidney transplants and the ever-increasing waiting time, the avoidance of PLNF transplants may be unwarranted especially in patients who have been enlisted for a long time.

Donor-specific antibodies detected by single antigen beads alone can help risk stratify patients undergoing retransplantation across a repeat HLA mismatch

“…[26][27][28] Patients with DSA detected by SAB alone may be considered at higher immunological risk but do not necessarily represent a group of patients in whom transplantation is contraindicated. [26][27][28] Patients with DSA detected by SAB alone may be considered at higher immunological risk but do not necessarily represent a group of patients in whom transplantation is contraindicated.…”

“…The clinical relevance of preformed DSA detected by SAB in the absence of a positive crossmatch remains another area of uncertainty. [26][27][28] Patients with DSA detected by SAB alone may be considered at higher immunological risk but do not necessarily represent a group of patients in whom transplantation is contraindicated. 29,30 Besides the presence of an RMM, retransplantation outcomes have also been shown to be related to other clinical characteristics related to primary transplant failure; namely rejection as the cause of failure, longevity of graft and time to retransplantation.…”

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

“…Unlike other studies, we excluded patients who showed CDC-FC- but had pretranspant DSA. The reasons were; 1) relatively small number ( n = 21), 2) recent meta-analysis demonstrating low level DSA detected by Luminex alone couldn’t affect short to medium posttransplant outcome [15]. So, we thought that including those patients would make the analysis complicated rather than resulted in better risk stratification according to HLA antibody strength.…”

“…Patients under 18 years of age, those receiving kidney transplants from HLA-identical siblings, ABO incompatible KT, those taking cyclosporin primarily as an immunosuppressant, and those lacking findings of pretransplant DSA or FC were excluded. Cases of negative crossmatch with DSA ( n = 21) were excluded in accordance with the recent report on non-inferior graft survival [15]. Furthermore, patients presenting positive T-cell but negative B-cell crossmatches and positive FC without DSA were excluded owing to potential technical errors.…”

Out with the old, in with the new: Virtual versus physical crossmatching in the modern era

“…A recent meta-analysis of these types of situations was performed and the culmination of the data showed no significant difference in acute rejection, graft failure, or patient mortality between patients with a negative FCXM and either a positive or negative VXM. 66 While this is an interesting observation, there were some issues with this review. First, there was no clear indication that denatured antigens, nonexposed epitopes, or bead abnormalities were excluded.…”