Analysis of Luminex-based Algorithms to Define Unacceptable HLA Antibodies in CDC-crossmatch Negative Kidney Transplant Recipients
Daniel ZecherChristian BachAdrian PreissChristoph StaudnerKirsten UtpatelMatthias EvertBettina JungTobias BerglerCarsten A. BögerBernd M. SpriewaldBernhard Banas
14
Citation
23
Reference
10
Related Paper
Citation Trend
Abstract:
HLA-specific antibodies detected by solid phase assays are increasingly used to define unacceptable HLA antigen mismatches (UAM) before renal transplantation. The accuracy of this approach is unclear.Day of transplant sera from 211 complement-dependent cytotoxicity crossmatch-negative patients were retrospectively analyzed for donor-specific anti-HLA antibodies (DSA) using Luminex technology. HLA were defined as UAM if DSA had mean fluorescence intensity above (I) 3000 (patients retransplanted and those with DSA against HLA class I and II) or 5000 (all other patients), (II) 5000 for HLA-A, -B, and -DR and 10 000 for HLA DQ or (III) 10 000 (all HLA). We then studied the accuracy of these algorithms to identify patients with antibody-mediated rejection (AMR) and graft loss. UAM were also determined in 256 transplant candidates and vPRA levels calculated.At transplantation, 67 of 211 patients had DSA. Of these, 31 (algorithm I), 24 (II) and 17 (III) had UAM. Nine (I and II) and 8 (III) of 11 early AMR episodes and 7 (I), 6 (II) and 5 (III) of 9 graft losses occurred in UAM-positive patients during 4.9 years of follow-up. Algorithms I and II identified patients with persistently lower glomerular filtration rate even in the absence of overt AMR. Of the waiting list patients, 22-33% had UAM with median virtual panel reactive antibody of 69.2% to 79.1%.Algorithms I and II had comparable efficacy but were superior to Algorithm III in identifying at-risk patients at an acceptable false-positive rate. However, Luminex-defined UAM significantly restrict the donor pool of affected patients, which might prolong waiting time.Keywords:
Donor-Specific Antibodies
Transplanted kidney
Cite
Citations (9)
Kidney transplants are at risk for so far unavoidable ischemia-reperfusion injury. Several experimental kidney transplantation models are available to study this injury, but all have their own limitations. Here, we describe precision-cut kidney slices (PCKS) as a novel model of kidney ischemia-reperfusion injury in comparison with pig and human kidney transplantation. Following bilateral nephrectomy in pigs, we applied warm ischemia (1h), cold ischemia (20h) and a reperfusion period (4h) to one whole kidney undergoing transplantation to a recipient pig and, in parallel, established PCKS undergoing ischemia and modeled reperfusion. Histopathological assessment revealed the presence of some but not all morphological features of tubular injury in PCKS as seen in pig kidney transplantation. RNAseq demonstrated that the majority of changes occurred after reperfusion only, with a partial overlap between PCKS and kidney transplantation, with some differences in transcriptional response attributable to systemic inflammatory responses and immune cell migration. Comparison of PCKS and pig kidney transplantation with RNAseq data from human kidney biopsies by gene set enrichment analysis revealed that both PCKS and pig kidney transplantation reproduced the post-reperfusion pattern of human kidney transplantation. In contrast, only post-cold ischemia PCKS and pig kidney partially resembled the gene set of human acute kidney injury. Overall, the present study established that a PCKS protocol can model kidney transplantation and its reperfusion-related damage on a histological and a transcriptomic level. PCKS may thus expand the toolbox for developing novel therapeutic strategies against ischemia-reperfusion injury.
Cite
Citations (0)
Options for Patients with End-Stage Renal DiseaseTransplantation ImmunobiologyHistocomatibility Testing, Crossmatching, and Allocation of Cadaveric Kidney TransplantsImmunosuppressive Medications and Protocols for Kidney TransplantationLiving and Cadaveric Kidney DonationEvaluation of the Transplant RecipientThe Transplant Operation and its Surgical ComplicationsThe First two Posttransplantation MonthsLong-Term Posttransplantation Management and ComplicationsInfectious Complications of Kidney Transplantation and their ManagementHepatitis in Kidney TransplantationDiagnostic Imaging in Kidney TransplantationPathology of Kidney TransplantationKidney and Kidney-Pancreas Transplantation in Diabetic PatientsKidney Transplantation in ChildrenPsychiatric Aspects of Kidney TransplantationEthical and Legal Issues in Kidney TransplantationNutrition in the Kidney Transplant RecipientPsychosocial and Financial Issues in Kidney Transplantatio
Cadaveric spasm
Artificial kidney
Cite
Citations (237)
The objective of the present study was to describe kidney temperature variations during transplantation and to identify the factors responsible for kidney warming. Kidney temperature was recorded steadily during transplantation. Kidney weight, body mass index (BMI), second warm ischemia time (t), and kidney temperature at the time of being placed in the recipient were analyzed so that we could evaluate their influence on kidney temperature and on kidney warming during transplantation. Kidney temperature at the time of removal from the container was 1.6 degrees C and 6. 3 degrees C when the kidney was placed in the recipient. Kidney temperature in the recipient depended on kidney temperature after serum washing (P<0.0001), but was independent of kidney preparation time (P=0.94). Then, kidney temperature (T) increased according to the logarithmic curve given in the following equation: T=7.2 ln(t)-0.6. Kidney temperature at the end of anastomosis was 26.7 degrees C. Kidney warming speed was 0.48 degrees/min and was dependent on the length of time of vascular anastomosis (P<0.0001). Kidney weight decreased the kidney warming speed (P=0.02). In conclusion, kidney warming increases slowly during ex vivo preparation. Kidney temperature stays below the damaging ischemic temperature of 18 degrees C. Because of its major impact on kidney warming, it is desirable that vascular anastomosis time be reduced, and, consequently, ex vivo kidney preparation needs to be meticulous.
Cite
Citations (30)
Cite
Citations (39)
Panel reactive antibody
Donor-Specific Antibodies
Cite
Citations (0)
Objectives To investigate the impact of donor kidney volume and renal function on posttransplant graft function.Methods The correlations of the donor kidney volnine , the renal function and the mean SCr 13.2 months after kidney transplantation were studied in 53 living kidney donor-recipient pairs.Results The donor kidney volume had an obvious impact on the mean SCr 13.2 months after kidney transplantation(r=0.539,p＜0.01).A donor kidney volume greater than 110 cm3 was independently associate with better GFR at the mean 13.2 months post-transplant when compared to recipients of lower donor kidney volume(81.19+16.5 vs 66.97+12.72 ml/min,p＜0.01);the donor kidney ideal function Wes positively correlated with the mean SCr 13.2months post-operation(r=0.363,p＜0.01).Conclusions The donor kidney volume and the rehal function are important factors that influence long-term allograft function after kidney transplantation.It is suggested that larger and good-functional kidneys should be preferred when selecting from otherwise similar living donors.
Key words:
Kidney Transplantation
Cite
Citations (0)
In kidney transplantation, short-term allograft survival has improved due to improvements in acute rejection episodes without corresponding improvements in long-term survival. Although current organ allocation algorithms take into account human leukocyte antigen (HLA) matching to reduce antidonor alloimmune responses, it is likely that genomic variation at non-HLA loci (ie, non-HLA donor–recipient [D–R] pair mismatches) play a role in the "non-self" responses and ultimately affect long-term allograft survival. Existing data from both animal models and human studies suggest an association between non-HLA D–R mismatches and kidney allograft outcomes. In this minireview, we examine existing and emerging data and discuss putative mechanisms on the role of non-HLA D–R mismatches on long-term allograft outcomes in kidney transplantation. In kidney transplantation, short-term allograft survival has improved due to improvements in acute rejection episodes without corresponding improvements in long-term survival. Although current organ allocation algorithms take into account human leukocyte antigen (HLA) matching to reduce antidonor alloimmune responses, it is likely that genomic variation at non-HLA loci (ie, non-HLA donor–recipient [D–R] pair mismatches) play a role in the "non-self" responses and ultimately affect long-term allograft survival. Existing data from both animal models and human studies suggest an association between non-HLA D–R mismatches and kidney allograft outcomes. In this minireview, we examine existing and emerging data and discuss putative mechanisms on the role of non-HLA D–R mismatches on long-term allograft outcomes in kidney transplantation.
Histocompatibility Testing
Cite
Citations (13)
Antibodies (Abs) directed against human leukocyte antigens (HLA) are associated with antibody mediated rejection and graft failure after kidney transplantation, but the problem of discrimination between relevant and irrelevant HLA Abs detected by solid phase assays has still not been solved. The new C1q assay based on single antigen beads detects a subset of HLA Abs that is able to fix the complement component C1. In this preliminary study we retrospectively analyzed C1q fixing HLA Abs in 20 selected living kidney transplantation donor/recipient pairs. Group A comprised 9 recipients with biopsy proven acute rejection. Six of them had positive pretransplant flow cytometric T cell crossmatches (FCXM). Group B comprised 11 recipients with negative FCXM results and without rejection. We measured pretransplant IgG HLA Abs using single antigen beads and subsequently also C1q fixing HLA Abs. Pretransplant testing of group A revealed 7 (78%) HLA-class I positive patients [3 (43%) with donor-specific Abs (DSA)] and 6 (67%) HLA-class II positive patients [2 (33%) with DSA]. Testing of group B resulted in comparable results: 8 (72%) HLA-class I positive patients [2 (25%) with DSA], and 7 (64%) HLA-class II positive patients [1 (14%) with DSA], respectively. Subsequent analysis of C1q fixing Abs within group A confirmed two patients to be positive for HLA-class I Abs, and only one for HLA-class II. DSA was not detected in any patient of group A. Group B was completely negative. Therefore, a trend to a higher risk for humoral rejections could be observed when pretransplant C1q positivity was present (p=0.07, RR 2.83, OR 12.38). Two of the three C1q positive patients were also positive for pretransplant cytotoxic antibodies, which supports the validity of the C1q assay. Our study indicates a potential improvement of HLA antibody analysis with single antigen beads using the C1q assay. A multicenter study has been initiated to confirm our preliminary results.
Donor-Specific Antibodies
Panel reactive antibody
Isoantibodies
Cite
Citations (0)
Donor-Specific Antibodies
HLA-C
Histocompatibility Testing
Histocompatibility
Isoantibodies
Cite
Citations (0)