Abstract Numerous studies have shown that circulating donor-specific antibodies targeting human leukocyte antigen (HLA) are associated with accelerated renal transplant failure, but many patients ...with these antibodies have good graft function. The aim of our study was to investigate the long-term graft function and survival in patients with de novo post-transplant donor-specific anti-HLA antibodies (DSA). Our prospective study included 78 consecutive recipients with a negative crossmatch before transplantation. Recipient serum samples were assayed for DSA in week 2 and 1, 3, 6, 9, 12 months after transplantation using a complement-dependent lymphocytotoxic technique with donor lymphocytes. Additionally, patients with DSA and stable renal function in the first year were tested with a more sensitive flow-panel-reactive antibody. DSA were present in 34 (44%) of our patients during the first 12 months after transplantation. Biopsy-proved acute rejection occurred in 11 DSA-positive and 10 DSA-negative patients. Seven DSA-positive patients had antibody-mediated rejection and no DSA-negative ones developed humoral rejection. The serum creatinine level in DSA-positive patients was significantly higher (2.48 vs 1.43 mg/dL) in year 5. The 13 (38%) DSA-positive patients with good graft function in month 12 were stable during a 5-year follow-up: their serum creatinine was 1.46 ± 0.4 in year 1 and 1.56 ± 0.4 mg/dL in year 5 and nobody lost their allograft. One- and 5- year graft survivals were appropriately 85% and 59% in DSA-positive patients compared to 93% and 93% in DSA-negative patients. To sum up, post-transplant DSA had a significant influence on kidney function and graft survival but in 38% of patients the presence of DSA did not decrease a 5-year renal function. A good renal allograft function in the presence of DSA in the first year after transplantation and cessation of their production in the subsequent years may be a good prognostic marker for a long-term allograft function and survival.
Abstract Impaired renal graft function is a matter of particular concern during post-transplantation care because low estimated glomerular filtration rate (eGFR) is a risk factor for graft loss. The ...aim of the study was to assess risk factors for inferior outcomes of kidney transplantations with low eGFRs. We identified 72 patients who underwent transplantation between 1999 and 2005 who had chronic renal graft dysfunction after 6 months post-transplantation (eGFR < 40 mL/min/1.73 m2 ), received a kidney transplant between 1999 and 2005, and were treated in one center through the entire post-transplantation course. Three patients who were lost for follow up after 6.4, 6.7, and 8.5 years are not included in this analysis. A group of 23 patients (33%) had chronic kidney disease stage 4 (eGFR < 30 mL/min/1.73 m2 ) at 6 months. In 39 patients (56%), delayed graft function was diagnosed. Forty-eight patients (70%) had at least one episode of acute graft rejection. Results were confirmed using biopsy in 39 patients. Eight patients (12%) died and 35 patients (51%) lost their grafts between 1.6 and 14 years (median, 6.3 years). The remaining 26 (38%) patients have still functioning allografts 11 years after transplantation (median). The initial immunosuppression included calcineurin inhibitor (CNI) in all cases. At the end of study, 6 (8.3%) patients received mammalian target of rapamycin inhibitor plus steroids, whereas the remaining were treated with CNIs. Improvement of kidney function by 15% was observed in 23% of the studied population between 6 and 24 months. This satisfactory outcome was a result of the careful follow-up examinations and comprehensive medical care provided by our dedicated staff of nurses and physicians. Improvement of kidney function may reflect a state of immune quiescence in some patients which allows them to sustain a functioning kidney despite injury.
This study focuses on the cytokine genes expression after brain-death, ischemia-reperfusion injury, and during allograft rejection.
A total of 49 needle core biopsies from kidney transplant ...recipients, performed before and during transplantation procedures were studied. The first biopsy was taken during procurement of the organ, the second after cold ischemia, and the third after approximately 30 min of reperfusion. We also assessed 34 allograft biopsies obtained during acute rejection. Tubular and glomerular expression of interferon (IFN)-gamma, transforming growth factor (TGF)-beta1, platelet-desired growth factor-B (PDGF-B), interleukin (IL)-2, IL-6, IL-10 mRNA was analyzed with reverse-transcription polymerase chain reaction (RT-PCR) in situ technique, which allows to detect a few copies of the target gene without destruction of the tissue architecture.
Compared with normal kidney tissue from living donor, high gene expression of IFN-gamma, TGF-beta1, PDGF-B, IL-2, IL-6, and IL-10 was detected in all procurement specimens. After reperfusion gene expressions of IL-2, IL-6, and IL-10 were significantly upregulated in renal tubules compared to biopsies taken after cold ischemia. The gene expression of IFN-gamma, TGF-beta1, and PDGF-B remained stable after organ procurement, during cold ischemia, and after reperfusion. Gene expression of IFN-gamma, IL-2, IL-6, IL-10, and PDGF-B in procurement biopsies, as well as in those taken after cold ischemia and reperfusion, were significantly higher than during the period of acute rejection.
The data presented herein strongly point out the importance of the immunological and morphological injury that occurs before and during transplantation. The increase of inflammatory response after brain death is important for further stimulation of the immune response and long-term kidney survival.
The cross-sections of relativistic deuteron reactions on natural copper were studied in detail by means of activation method. The copper foils were irradiated during experiments with the model ...spallation targets in the Joint Institute for Nuclear Research. The irradiation of activation samples was performed by beams in the energy range from 1 to 8GeV. Residual nuclides were measured by the gamma spectrometry. While the EXFOR database contains sets of data for relativistic proton reactions, data for deuteron reactions in this energy range are almost missing. Lack of such experimental cross-section values prevents the use of copper foils from beam integral monitoring. For this reason our experiments focused on their measurement and completely new data were obtained in the energy region where no experimental data have been available so far. The copper monitors with their low sensitivity to fast neutrons will contribute to improvement of the beam integral determination during accelerator-driven system studies.
Current trend in nuclear reactor physics is a transition from technologies using thermal neutrons to technologies utilizing fast neutrons. Unfortunately focus was put mainly on the thermal neutrons ...for a long time and lead to very good knowledge about this low energy region, but very scarce coverage of the high energy region. This means that there is a gap in the knowledge of excitation functions for higher energies. This gap spreads from 20 MeV up to 1 GeV and higher. This is exactly the energy region needed for description of advanced nuclear systems such as accelerator driven systems (ADS). Our group from Nuclear Physics Institute (NPI) of the CAS is a member of an international collaboration Energy & Transmutation of Radioactive Waste (E&T RAW). This collaboration focuses on ADS for many years. In order to measure neutron field within ADS models it is necessary to know excitation functions of reactions used to monitor the neutron field. In many cases there are almost no experimental data for suitable reactions. Worse and quite common case is that there are no data at all. Therefore we are also focusing on measurements of these data in order to fill the databases as well as to allow further improvements of codes for nuclear data calculations.
Abstract Background The most frequent cause of kidney allograft loss is chronic allograft injury, often with proteinuria as the clinical feature. Occurrence of proteinuria late after kidney ...transplantation is associated with worse graft function and patient survival. Aim The aim of the study was to assess plasma and urine matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in proteinuric renal transplant recipients (RTRs). The factors were determined by enzyme-linked immunosorbent assay in 150 RTRs (51 women and 99 men), aged 49.2 ± 11.5 years, at mean 73.4 ± 41.2 months after kidney transplantation (range: 12 to 240 months). Results Proteinuric RTRs compared with non-proteinuric RTRs had higher median plasma MMP-2 ( P = .012), TIMP-1 ( P = .0003), and TIMP-2 ( P = .0021) concentrations, as well as higher urine MMP-2 ( P < .0001) excretion. The presence of proteinuria had no impact on plasma MMP-9 and urine MMP-9, TIMP-1, and TIMP-2. Proteinuria and estimated daily proteinuria (uPr:uCr) correlated positively with plasma MMP-2 (rs = 0.226, P = .0054 and rs = 0.241, P = .003), TIMP-1 (rs = 0.305, P = .00015 and rs = 0.323, P = .000055), TIMP-2 (rs = 0.273, P = .0007 and rs = 0.269, P = .001) and urine MMP-2 (rs = 0.464, P < .0001 and rs = 0.487, P < .0001), respectively. Proteinuric RTRs had impaired graft function with higher median serum creatinine concentrations (1.91 1.60–2.43 mg/dL versus 1.41 1.20–1.65 mg/dL, P < .00001) and lower estimated glomerular filtration rate (36 28–45 mL/min/1.73 m2 versus 53 43–61 mL/min/1.73 m2 , P < .00001) than RTRs without proteinuria. Conclusions Our research revealed that in RTRs, proteinuria was significantly associated with increased concentrations of enzymes involved in extracellular matrix (ECM) degradation: plasma MMP-2, TIMP-1, TIMP-2, and urine MMP-2. Findings strongly emphasize increased plasma TIMPs in proteinuric RTRs that inhibit degradation of ECM by MMPs and favor excessive deposition of ECM proteins.
Abstract Background Advanced age of renal transplant recipients (RTRs) has a negative impact on kidney allograft survival through impaired extracellular matrix degradation by the matrix ...metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system. Moreover, older RTRs are at risk of smoldering inflammation, known as inflammaging. Aim The aim of the study was to assess the impact of a RTR's age on plasma and urine concentrations of interleukin 6 (IL-6), chemokine ligand 2 (CCL2), and the MMPs/TIMPs system. Material and Methods One hundred fifty adult RTRs (8.7% ≥ 65 years) and 37 adult healthy volunteers (10.8% ≥ 65 years) were enrolled in the study. The studied factors (IL-6, CCL2, MMP-2, MMP-9, TIMP-1 and TIMP-2) were quantified in plasma and urine with enzyme-linked immunosorbent assay. The Mann-Whitney U test and Spearman's (rs ) rank correlation were applied, and differences with a P < .05 were considered statistically significant. Results There was a weak but significant positive correlation between increasing RTR's age and plasma IL-6 (rs = 0.18, P = .028), CCL2 (rs = 0.27, P = .001), and MMP-2 (rs = 0.20, P = .017), as well as urine CCL2 (rs = 0.16, P = 0.050) and TIMP-1 (rs = 0.20, P = .014) concentrations. Conclusions Advancing age of RTRs correlates with increasing plasma IL-6 and CCL2 concentrations, reflecting smoldering inflammation (known as inflammaging) and alterations in MMPs/TIMPs profiles, especially with increased plasma MMP-2 and urine TIMP-1 concentrations.
The international collaboration Energy and Transmutation of Radioactive Waste (E&T RAW) performed intensive studies of several simple accelerator-driven system (ADS) setups consisting of lead, ...uranium and graphite which were irradiated by relativistic proton and deuteron beams in the past years at the Joint Institute for Nuclear Research (JINR) in Dubna, Russia. The most recent setup called Quinta, consisting of natural uranium target-blanket and lead shielding, was irradiated by deuteron beams in the energy range between 1 and 8 GeV in three accelerator runs at JINR Nuclotron in 2011 and 2012 with yttrium samples among others inserted inside the setup to measure the neutron flux in various places. Suitable activation detectors serve as one of possible tools for monitoring of proton and deuteron beams and for measurements of neutron field distribution in ADS studies. Yttrium is one of such suitable materials for monitoring of high energy neutrons. Various threshold reactions can be observed in yttrium samples. The yields of isotopes produced in the samples were determined using the activation method. Monte Carlo simulations of the reaction rates leading to production of different isotopes were performed in the MCNPX transport code and compared with the experimental results obtained from the yttrium samples.
Abstract Extracorporeal photopheresis (ECP) is considered a promising immunomodulatory therapy of acute allograft rejection in organ transplantation and graft-versus-host disease. Our aim was to ...investigate the biological responses of 10 patients who underwent kidney transplantation with ECP as prophylactic treatment. They received conventional immunosuppressive therapy plus ECP immediately after transplantation: 12 to 16 applications over the course of 2.5 months. ECP procedures were performed using an automated system for leukocyte separation and photoactivation with methoxsalen. All recipients were followed by estimated glomerular filtration rate (eGFR) and peripheral T, B, natural killer, T-regulatory (Treg) and dendritic cells (DC) counts and phenotypes. An acute rejection episode appeared in one control group recipient. The ECP group showed a positive trend to an higher GFR at months 3 (53 ± 11 vs 47.1 ± 9; P = .17) and 6 (67.5 ± 10 vs 53.6 ± 3; P = .03, Wilcoxon test). An increased percentage of Treg (CD3+ CD4+ CD25+ ) among the total CD3 cell count (4.9% ± 1% to 9.4% ± 15%) as well as inducible Treg (CD3+ CD8+ CD28− ) was observed among CD3 cells (3.3% ± 3% to 11.8% ± 8%, P = .025) within 3 months of ECP treatment. A significant difference in the percentage of Treg was noted at month 3 (completed ECP) between the ECP and the control groups (9.4% ± 15% vs 3% ± 1%; P = .01). Addition of ECP to standard immunosuppression was associated with a significantly higher GFR at 6 months and with a significant increase in natural Treg among CD3 cells.
Improvements of the Monte Carlo transport codes and cross-section libraries are very important steps towards usage of the accelerator-driven transmutation systems. We have conducted a lot of ...benchmark experiments with different set-ups consisting of lead, natural uranium and moderator irradiated by relativistic protons and deuterons within framework of the collaboration "Energy and Transmutation of Radioactive Waste". Unfortunately, the knowledge of the total or partial cross-sections of important reactions is insufficient. Due to this reason we have started extensive studies of different reaction cross-sections. We measure cross-sections of important neutron reactions by means of the quasi-monoenergetic neutron sources based on the cyclotrons at Nuclear Physics Institute in e and at The Svedberg Laboratory in Uppsala. Measurements of partial cross-sections of relativistic deuteron reactions were the second direction of our studies. The new results obtained during last years will be shown. Possible use of these data for improvement of libraries, models and benchmark studies will be discussed.
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