Number Of HLA Matches Research Articles

Uncovering a Long-term Graft Survival Advantage Afforded by Infant Renal Transplants-An Organ Procurement and Transplantation Network Database Analysis.

Background.Renal transplants (Tx) are performed infrequently in infants, due to concerns related to poor outcomes. The aim of our study was to compare graft failure rates in infant (<1 y) renal Tx recipients compared with older children.Methods.Retrospective cohort study of pediatric renal Tx recipients from 2000 to 2015, using the Organ Procurement and Transplant Network database. A log-linear event history regression model for time to graft failure, adjusting for age group and important confounders, was used to estimate post-Tx graft failure probabilities.Results.In 2696 Tx followed for a median of 6.1 y, 704 failures were observed. Significant predictors of graft failure were year of Tx (for each year after 2000, rates were 8.6% lower), Black race-ethnicity (63% higher compared with Whites), and number of HLA matches. For infants (n = 27), estimated graft failure percentage (95% confidence interval) within the first 1-, 2-, and 5-y post-Tx were 10.4 (0.1–21.1), 11.9 (1.2–22.6), and 16.4 (4.9–27.9). For the 1- to 11-y-olds (n = 1429), these were 3.8 (3.0–4.6), 6.3 (5.4–7.3), and 13.6 (12.2–15.0), respectively, and for the 12+ y olds (n = 1240), they were 3.8 (3.1–4.5), 8.1 (7.2–9.0), and 19.9 (18.1–21.7), respectively (P < 0.001 for 5-y graft failure rate across age groups).Conclusions.Infant renal Tx recipients experience a higher graft failure rate in the first year, compared with older cohorts, but over longer intervals, cumulative failure rates are comparable or even lower. To minimize early graft losses such Tx should be performed in experienced centers.

Monocyte-to-High-Density Lipoprotein Cholesterol Ratio Is Independently Associated With All-Cause Mortality in Deceased Donor Kidney Transplant Recipients.

The primary objective of this study was to evaluate the impact of monocyte-to-high-density lipoprotein cholesterol ratio on all-cause mortality in deceased donor kidney transplant recipients. This was a retrospective observational study in which all deceased donor kidney transplant recipients were included. Relevant data for analyses included clinical and demographic features, laboratory values, number of HLA matches, occurrence of delayed graft function, cold ischemia time, and survival status. Kaplan-Meier survival analysis and Cox proportional hazards analysis were performed to determine the effects of monocyte-to-high-density lipoprotein cholesterol ratio on all-cause mortality. Our study included 325 deceased donor kidney transplant recipients (43.1% females, mean age of 44.5 ± 11.2 years). Median value of monocyte-to-high-density lipoprotein cholesterol ratio was 14.0 (interquartile range, 9.94-21.03). The total median observation time was 227 weeks (range, 115-345 weeks). Twenty deaths (12.3%) occurred during the follow-up period in recipients with monocyte-to-highdensity lipoprotein cholesterol ratio below median value, whereas 47 deaths (29%) occurred in recipients with ratio above the median (P < .001). Log-rank test showed significantly higher mortality in the group with monocyte-to high density lipoprotein cholesterol ratio higher than median (P = .001). In the multivariate Cox model, delayed graft function, duration of dialysis, cold ischemia time, and monocyte-to-high-density lipoprotein cholesterol ratio group appeared as independent predictors of all-cause mortality. Monocyte-to-high-density lipoprotein cholesterol ratio before kidney transplant seems to affect survival independently in deceased donor kidney transplant recipients.

Therapeutic EBV-specific T cell cytotoxicity against allogeneic LCLs in vitro directly correlates to intracellular IFNγ/TNFα expression in response to EBV peptide stimulation

Background & Aim SNBTS has been involved in the manufacture of Epstein-Barr virus-specific T cells (EBV-VST) in treatment of post-transplant lymphroliferative disorder (PTLD) for over 20 years. Manufacture of cells for clinical use relies on comprehensive QC analysis to assess product safety, dose, identity, functionality and stability. We have developed an in vitro cytotoxicity assay of EBV-VST against EBV-infected lymphoblastoid cell line (LCL) targets to measure specific lysis compared to controls. Since the LCLs required for this assay may contain live virus, in the advancing regulatory setting this assay is not easily transferable to an accredited QC lab. The aim of this study was to investigate if VST cytotoxicity directly correlated to any other cytotoxic T cell functional assays such as cytokine production or expression of degranulation markers. Methods, Results & Conclusion Cryopreserved EBV-VST products were thawed, counted, and split for use in both a cytotoxicity assay and intracellular cytokine/ degranulation assay. For the cytotoxicity assay, HLA-matched and unmatched LCLs were labeled with PKH67, and then co-cultured alongside EBV-VSTs at increasing VST to LCL ratios against suitable controls. Plates were incubated for 5 hours, and cells subsequently labeled with Annexin V and DRAQ7 to assess target apoptotis and necrosis by flow cytometry. For the intracellular assay, EBV-VSTs were stimulated for 5 hours with EBV consensus peptides and then labeled with surface and intracellular markers in the following flow cytomeric panel: CD8, CD4, CD45RO, CD107a, Perforin, Granzyme B, IFNγ, TNFα, IL-2 and DRAQ7. Both assays were performed from the same start material at same time to ensure a direct comparison. The percentage of IFNγ/TNFα co-expressing cells in response to EBV peptide stimulation positively correlated with specific lysis of HLA-matched target LCLs in EBV-VST co-cultures (R2= 0.5602, p=0.008, n=12). No correlation of LCL specific lysis was seen with any of the other degranulation markers, and interestingly no correlation seen with other product-variable parameters (VST viability, CD8/CD4 ratio, number of HLA matches) suggesting these have less direct impact on overall killing efficiency. Flow cytometric analysis of IFNγ/TNFα expression in response to EBV peptide stimulation is an accurate surrogate marker of EBV-infected LCL killing by VSTs, and therefore presents a valid, safe and compliant alternative functional characterisation method to the conventional LCL cytotoxicity assay.

The impact of slow graft function on graft outcome is comparable to delayed graft function in deceased donor kidney transplantation.

Slow graft function (SGF) can influence overall prognosis in patients receiving deceased donor kidney transplantation (DKT). However, the impact of SGF on renal function remains uncertain. We investigated retrospectively renal function in cases with SGF compared with early graft function (EGF) and delayed graft function (DGF). Renal function after transplantation was analyzed in 199 patients who underwent DKT. Patients were classified into 130 (65.3 %) cases with EGF, 27 (13.6 %) cases with SGF, 6 (3.0 %) cases with DGF and one dialysis (DGF1), and 36 (18.1 %) cases with DGF and two or more dialyses (DGF2). The 1-year estimated glomerular filtration rate (eGFR) in the SGF group was lower than that in the EGF group (P = 0.027), but the rate of eGFR decline did not differ between the groups. The risk factors for renal function were evaluated using the area under the eGFR curve over 3 years (AUCeGFR). Donor age was negatively, and recipient age and the number of HLA matches were positively correlated with the AUCeGFR (all P < 0.05). A multivariate analysis revealed that the AUCeGFR was lower in cases of younger recipient age, older donor age, and acute rejection (all P < 0.05). The AUCeGFR was significantly lower in the SGF and DGF2 groups compared with the EGF group (P = 0.031 and 0.006, respectively). SGF may be an independent risk factor for poor renal function after DKT. Moreover, it was comparable to DGF. Efforts should be dedicated to minimizing the development of SGF and DGF.

Innate immune proteins, SP-A, SP-D and MBL-A, are expressed by murine testicular germ cells and are positively regulated by testosterone

Oocyte donation (OD) enables women with various causes of reproductive failure to conceive, but is accompanied with a high risk for certain pregnancy disorders. Possibly, the allogeneic nature of the fetus in OD pregnancies plays a role in the development of these disorders. In this study, we investigated whether there is a selection for some degree of HLA matching in successful and uncomplicated OD pregnancies. Mothers and children from OD pregnancies that made use of unrelated donors (n=75) were typed for HLA-A,-B,-C,-DR,-DQ and the observed number of HLA matches of the child was compared with the expected number of HLA matches. Moreover, we studied the possibility of a preferential selection for maternal KIR and fetal C combinations. We observed a significantly higher level of HLA matching betweenmother and child than expected by chance. Especially the incidenceof childrenwith5ormoreHLAmatches,which is the situation in autologous pregnancy, was higher than expected. A higher level of matching was shown especially for HLA class I, while no significant differences were observed for the individual HLA loci. With respect to maternal KIR and fetal HLA-C no selection for a favorable combination was found. Larger observational studies including uncomplicated, preeclamptic and aborted pregnancies are essential to determine to what extent HLA matching affects the outcome of OD pregnancies.

Ureteric Stent in Renal Transplantation

IntroductionSeveral techniques can be used to accomplish the ureteroneocystostomy in kidney transplantation. A ureteral catheter is a prophylactic measure to avoid urological complications (UC) of stenosis and/or fistula. In this study we evaluate the influence of using a ureteral stent upon the rate of UC in renal transplantation. Patients and methodsRetrospective review of 2061 kidney transplants (75 living and 1986 cadaveric donors) for 1360 male and 684 female recipients, from July 14, 1991, to January 13, 2012, with a minimum follow-up of 6 months A double J stent (JJ) was used in 1890 an external tumor (ET) catheter in 52 and no catheter (NC) in 119 cases. ResultsMean recipient age was 44.66 ± 13.66 years. UC occurred in 5.9% among which ET showed 17.3%, 8.4% for NC, and 5.4% for JJ (P < .0005). Urological complications were more frequent when surgery duration exceeded 3 hours (8.8% vs 5.3% ≤ 3 hours; P = .003), using older donors organs (P = .048) and with higher donor weight (P = .009). No differences were observed related to recipient age, gender, or weight; donor gender; pretransplant dialysis time; cold ischemia time; type of donor (living vs cadaveric); number of HLA matches; or initial immunosuppression (mammalian target of rapamycin inhibitor vs other). On multivariate analysis, donor weight (odds ratio [OR]: 1.023; P = .015), use of a JJ vs ET (OR: 0.280; P = .005), and surgery time exceeding 3 hours (OR: 3.270; P < .0005) were independently associated with UC. ConclusionsCatheterization of the urinary anastomosis with a JJ was associated with fewer UC. This is especially important for grafts from heavier donors. The use of an external catheter which was associated with an high rate of UC, should be avoided.

The influence of hepatitis C virus genotypes on the outcome of liver transplantation.

The aim of this study was to report the influence of hepatitis C virus (HCV) genotypes and HLA matches on the outcome of liver transplantation, hepatitis recurrence, and progression to cirrhosis after transplantation. HCV genotypes were determined from pretransplantation sera and/or liver explant tissues from 202 patients with HCV-related end-stage liver disease. One hundred fifty patients with known infecting genotype for whom posttransplantation biopsy specimens were available or who had normal results of liver injury tests constituted the group analyzed. Patients were followed up for up to 4.5 years. Hepatitis activity index scores at the time of disease recurrence were used to assess disease activity. Cirrhosis was diagnosed by using histological evidence. The number of HLA matches with respect to A, B, DR, and DQ loci was determined. The rates of hepatitis recurrence were 25% and 75% at 1 year and 4 years, respectively; Kaplan-Meier survival analysis did not reveal significant differences between the infecting genotypes with respect to overall rates of survival or recurrence of hepatitis. At hepatitis recurrence, hepatitis activity index scores did not differ between the genotype groups. The distribution of infecting genotypes among the 7 patients who developed cirrhosis is reflective of pretransplantation distribution. Neither HLA site-specific nor total matches affected the rates of survival or disease recurrence. The infecting HCV genotype had no influence on the incidence or severity of recurrent hepatitis, rate of survival, or development of cirrhosis. HLA matching does not influence transplantation outcome for HCV-related disease.

Influence of chronic rejection on the occurrence of monoclonal gammapathies in renal transplant patients

To assess the frequency of monoclonal gammapathies (MG) and their origin in immunosuppressed renal transplant patients, a prospective study was conducted in 164 patients who underwent 165 consecutive renal transplantations (RT) from April 1986 to August 1991. Sera were tested by cellulose acetate electrophoresis before RT and every 3 months after RT, and those containing a monoclonal component were further investigated by immunoelectrophoresis and/or immunofixation. The immunosuppressive regimen in 69 cases (41.8%) consisted of the association cyclosporinc ‐ prednisone while 96 patients (58.2%) received azathioprine in combination. Sera were regularly monitored by serological assays to detect antibodies against cytomegalovirus (CMV), Epstein‐Barr virus (EBV) and hepatitis B virus. Renal function was evaluated every 6 months by measurement of serum creatinine and quantification of proteinuria. Mean duration of follow‐up was 31.2 months ±15.9 (range 4‐62.4). Thirty‐eight (23.03%) patients developed a MG during this period (26 men, 12 women, mean age: 43.4± 11 years). MG occurred early after RT (6.7 ±7 months) and were often transient (30/38 disappeared after a period of 8.4 ± 12 months). Twenty‐four of the 38 MG were of the gamma 2 ‐ kappa 2 immunologic type whereas 8 were of the biclonal or oligoclonal type. Only moderate quantities of monoclonal component were secreted (9.4 ±2 g/1). Clinical and laboratory examinations excluded the presence of lymphoproliferative disorders of multiple myeloma. No correlation was found for sex, age, underlying renal disease, immunosuppressive regimen, number of HLA matches, and viral infections. The number of acute rejection episodes was similar in the two groups. Conversely, MG were found with a higher frequency in the group of patients who had evidence of chronic rejection (13/27 vs 25/137, p&lt;0.01). Serum creatinine was higher in MG patients from the 36th month after RT (p&lt;0.05). No difference was noted for proteinuria. We conclude that MG are frequently encountered in RT, especially in patients with deteriorating renal function. Since MG results in the uncontrolled proliferation of a B‐cell clone, it can be assumed that chronic rejection favors the occurrence of MG by enhancing the imbalance between the T‐ and B‐cell immune system.

Why do patients with postsurgical acute tubular necrosis die?

We compared early (less than 70 days) cumulative survival, cause of death, and morbidity (defined as the number of organ system failures and reoperations) of 236 patients who needed dialysis for acute tubular necrosis (ATN) after transplantation with that of a control group of 215 transplant patients who had immediate renal function after transplantation. The patients were matched for age, number of transplants, time of transplantation, diabetic status, living-related vs cadaveric donor, and number of HLA matches. There were no differences in cumulative survival after transplantation, causes of death, organ system failure, or surgical complications as evident from the number of reoperations. The ATN patients' overall clinical course was similar to that described for other postsurgical patients with ATN in their native kidneys. We conclude that the poor survival and the surgical complications in patients with postoperative ATN are due to the basic disease and not to acute renal failure or to dialysis. To improve survival, research should be focused on the basic disease and the surgical procedures rather than on dialysis technique.