HADES is a high acceptance di-electron spectrometer operating at SIS18, GSI, Germany aimed at study of hadron-proton, hadron-nucleus and nucleus-nucleus collisions at 1-4 AGeV beam energies. The new ...electromagnetic calorimeter (ECal) was added to the experimental setup in order to measure γ-quanta and thus extend its capabilities in study of π0-, η-mesons, production of neutral hyperons and to improve electron-to-hadron separation for the partcles with momenta p > 300 MeV/c. The first data taking with the ECal detector was carried out in March 2019 when Ag+Ag collisions at 1.23 AGeV and 1.58 AGeV beam energies were studied. The methods of reconstruction of the γγ invariant mass spectra from these data are discussed. The analysis includes several steps: calibration of each module of the ECal detector, identification of γ-quanta, reconstruction of γγ invariant mass spectra and subtraction of combinatorial background. The obtained results show experimental capabilities of the new detector and, after efficiency corrections, will allow to normalize yields of other particles.
The role of non-HLA antibodies named antiendothelin A receptor antibodies is potentially significant but not established. The significance of the endothelin A receptor (ETAR) and its expression in ...renal biopsy has not been defined. We decided to evaluate the presence and relevance of ETARs in renal transplant biopsy for cause.
The aim of our study was to evaluate the immunoreactivity of the ETAR and its significance in patients who had a renal transplant biopsy due to deterioration of transplant function (biopsy for cause) with detailed characterization of staining in small and intermediate arteries of renal transplant biopsies.
Immunohistochemical expression of ETARs was analyzed in 162 renal transplant biopsies. Microscopic evaluation of ETAR expression (polyclonal antibody) was performed on paraffin sections. ETAR expression was analyzed in renal blood vessels (small and intermediate arteries) based on three-step scale.
We analyzed 154 patients who had renal allograft biopsy between 6 days and 24 years (median 597 days) after transplantation. Positive staining of ETAR in small and intermediate arteries was noticed in 9 patients. Among these patients, 4 had early biopsies (<3 months after transplantation), all developed acute tubular necrosis, and 1 developed additionally acute humoral rejection. Further, 4 patients had late biopsy (1-8 years after transplantation) and all developed characteristics of antibody mediated rejection. Lastly, 1 patient had no characteristic changes in the biopsy 4 months after transplantation. Graft loss 1 year after biopsy was higher in patients who were ETAR-positive but statistical significance was not achieved.
The expression of endothelin receptors in renal blood vessels (small and intermediate arteries) seems to be important in diagnosis of damage during acute tubular necrosis and antibody-mediated rejection.
HADES (High Acceptance Di-Electron Spectrometer) is located at the GSI (Helmholtzzentrum für Schwerionenforschung) Darmstadt. It is an experiment focused on the study of the hot and dense nuclear ...matter mainly via the detection of the di-lepton pairs. Electromagnetic CALorimeter (ECAL) was recently added to the HADES setup. This new subdetector allows measuring of photons from the decay of neutral mesons and resonances. It also allows to discriminate between electrons and pions in the high-momenta region over 400 MeV/c. ECAL follows same hexagonal geometry as HADES, i.e. it consists of six sectors in azimuth. The first four sectors were finished and commissioned in 2018. The first experiment with ECAL included in HADES setup took place on March 2019, investigating the Ag+Ag reaction at beam energy of 1.65 A GeV. During the commissioning, several issues popped up and they were addressed. The issues and their solution will be described in the article.
HADES is a large acceptance spectrometer operating at SIS18, GSI, Germany. It is aimed at exploration of QCD phase diagram at the ion beam energies of 1-2 AGeV in the region of high baryonic ...densities. The new segmented electromagnetic calorimeter (ECal) was built to extend experimental opportunities of the HADES detector. The electromagnetic calorimeter will allow to study new reaction channels involving the production of neutral mesons and neu-tral resonances in elementary and heavy-ion reactions via detection of their two photon decay. An additional advantage of such a device is the resulting improvement of the electron-to-pion separation at large momenta. The detector is based on 978 Cherenkov lead glass modules divided into 6 sectors, and it covers forward angles of 12° < θ < 45° and almost full azimuthal angle. Currently four out of six sectors planned are assembled in the experimental area. The first raw beam data obtained with the ECal detector in Ag+Ag reactions at 1.65 AGeV beam are presented.
The occurrence of anti-angiotensin II type 1 receptor (AT1R) antibodies is thought to be a risk factor for transplant injury, but the relationship of AT1R to graft loss in renal transplantation has ...not been assessed.
The aim of our study was to evaluate the expression of AT1R and its relationship with graft loss in patients who had a renal transplant biopsy for cause.
AT1R immunoreactivity was analyzed in 170 renal transplant biopsies. Immunohistochemical evaluation of AT1R expression was performed on 4 μm-thick paraffin sections mounted on silanized slides. AT1R expression was analyzed in 5 compartments: 1. glomeruli, 2. renal blood vessels (small and intermediate arteries), 3. peritubular capillaries, 4. tubular epithelium, and 5. interstitium based on a 3-step scale.
Initially we checked 170 consecutive samples of biopsies for the immunoreactivity of the AT1R.
The study finally included 118 renal transplant patients in 1-year observation after the biopsy. The renal allograft biopsy was performed between 6 days and 24 years after transplantation and the diagnosis was based on Banff criteria.
We observed positive immunostaining of AT1R in tubular epithelium in 26.3% (42/118) of patients. A total of 7 patients had staining assessed as 2 and 35 as 1. One year post-biopsy graft loss in the AT1R (+) patients was 35.7 % (15/42) compared to 14.5% (11/76) in the AT1R (-) group (P = .008).
The expression of AT1R in tubular epithelium of the biopsy for cause was associated with significantly higher graft loss. The relevance of AT1R should be considered for better transplant immunological risk assessment.
•Expression of AT1-receptors is evaluated in renal transplant biopsy.•AT1-receptors in tubular epithelium are associated with graft loss.•AT1-receptors in biopsy is considered as a marker of transplant deterioration.
Renal transplant candidates present immune dysregulation caused by chronic uremia, and deceased kidney donors present immune activation induced by brain death. Pretransplant donor and recipient ...immune-related gene expression were examined in the search for novel predictive biomarkers crosslinking recipient and donor pretransplant immune status with transplant outcome.
This study included 33 low-risk consecutive renal transplant recipients and matched deceased donors. The expression of 29 genes linked to tissue injury, T-cell activation, cell migration, and apoptosis were assessed in postreperfusion kidney biopsies, as well as 14 genes in pretransplant peripheral blood of the kidney recipients. Gene expression was analyzed with real-time polymerase chain reaction on custom-designed low-density arrays.
Donor MMP9 expression was related to delayed graft function occurrence (P = .036) and short term kidney allograft function (14th day rs = −0.44, P = .012; 1st month rs = −0.46, P = .013). Donor TGFB1 expression was associated with short- and long-term graft function (14th day rs = −0.47, P = .007; 3rd month rs = −0.63, P = .001; 6th month rs = −0.52, P = .010; 12th month rs = −0.45, P = .028; 24th month rs = −0.64, P = .003). Donor TGFB1 expression was not related to donor age (rs = 0.32, P = .081), which was also an independent factor influencing the outcome. Recipient gene expression was not related to graft function but determined the acute rejection risk. Recipient IFNG and, to a lesser extent, IL18 expression were protective against acute rejection (area under the curve AUC 0.84, P < .001, and AUC 0.79, P < .001, respectively).
Kidney transplant outcome depends on the interplay between donor-related immune factors, which mostly affect allograft function and recipient immune milieu, influencing an alloreactive response.
•Kidney transplant outcome depends on the interplay between donor and recipient immune factors.•Recipient IFNG and IL18 expression were protective against acute rejection.•Donor MMP9 expression was related to delayed and short-term allograft function.•Donor TGFB1 expression was associated with short- and long-term graft function.
Complement activation is considered one of the mediators of renal ischemia-reperfusion injury. Elevated levels of C5b-9, C3a, and C5a are detected in sera of deceased kidney donors. The goal of the ...study was to characterize the functional activity of complement pathways in donor sera and to assess their influence on transplant outcome.
Sixty-four deceased kidney donors (age 45 ± 16 years; 28 female, 36 male) and 27 healthy controls (age 42 ± 12 years; 14 female, 13 male) were enrolled in the study. The results of transplantation for the respective 122 kidney recipients were included in the analysis. The functional activities of classical (CP), lectin (LP), and alternative (AP) pathways were measured using Wielisa-kit (reference normal level = 100%). In most cases, decreased functional activity reflects the activation status of the pathway.
The median (interquartile range) functional activities of the pathways in donor sera were CP 118 (89–150)%, LP 80 (20–127)%, and AP 74 (50–89)%, and did not differ from the control values CP 110 (102–115)%, LP 81 (26–106)%, AP 76 (61–88)%. The frequency of pathway activation observed in controls was CP 0%, LP 11%, and AP 0%. Deceased donors did not differ in activation of classical (11%) and lectin (13%) pathways, but presented a higher rate of alternative pathway activation (19%, P = .03). No significant influence of any pathway functional activity or its activation was proved to influence the transplant outcome.
Complement activation via alternative pathway was observed in diseased donor sera. No predictive potential of donor complement functional activity on the transplant outcome could be proved.
•No correlation was found between functional complement activities in donors and KTx outcome.•Donor CRP correlates with AP functional complement activity.•In the diseased donors group the most activated complement pathway is AP.
The long-term burden of higher donor age on graft function and survival after kidney transplantation remains uncertain. Because both recipient and donor characteristics have evolved and the general ...population age is on the increase, we looked at the causes of kidney graft outcome.
The aim of this study was to evaluate the impact of different clinical parameters on long-term outcome of older-donor kidney transplantation. This retrospective study included 345 adult patients (58 patients received kidney from donors at least 55 years old) transplanted between January 1993 and December 2005 and were followed in one center throughout the post-transplant course (median, 9.4 years). Data included recipient and donor age, cold ischemia time, delayed graft function, panel reactive antibodies, HLA mismatch, time on dialysis, graft function at different time points, uric acid level, proteinuria, immunosuppression, and biopsy-proven rejection.
Improvement of estimated glomerular filtration rate at 36 months after transplantation was a good prognostic factor for long-term kidney function. Higher donor age decreased the chance for improvement of kidney function by 2.8% per year of life (P = .0244). Hyperuricemia was found in 46% of the study population; estimated glomerular filtration rate less than 50 mL/min/1.72 m2 was associated with hyperuricaemia. A higher uric acid level was associated with inferior kidney function in recipient of older kidneys. Graft failure occurred late (median, 6.3 years post-transplantation) in 26 (44.8%) of older-donor recipients and in 87 (30.3%) of the remaining patients.
Our results suggest an important association between older donor age and decreased allograft function in kidney recipients with elevated uric acid level. Recipients of older kidneys with normal uric acid level presented satisfactory outcomes.
•The long-term burden of older donor age on graft function and survival after kidney transplantation remains uncertain.•Improvement of eGFR during the 36 months after transplantation was a good prognostic factor for long-term kidney function.•Higher uric acid level was associated with inferior kidney function in recipients of older kidneys.•Recipients of older kidneys with normal uric acid level presented satisfactory outcomes.
Previously transplanted highly sensitized patients experience problems with subsequent transplantation. It is also difficult to provide optimal hemodynamic conditions during successive kidney ...transplantation in heart transplant recipients.
We present a case of a 56-year old patient with end-stage renal failure after heart transplantation performed 21 years ago and hemodialyzed using arteriovenous fistula. The patient had 69% panel-reactive antibodies, had been on the active waiting list since 2013, and presented 335 positive crossmatches with deceased donors. He also positively crossmatched with a potential living donor. Detailed examination of anti-HLA antibodies revealed the absence of IgG donor-specific antibodies and negative crossmatch with dithiothreitol-treated serum. The transplantation from his wife was performed with positive crossmatch after 4 plasma exchanges and thymoglobulin induction. Because sympathetic and parasympathetic denervation of the transplanted heart and the presence of arteriovenous fistula induced volume overload of the right heart, we used central venous pressure (CVP) and the PiCCO2 for postsurgical assessment of cardiac output.
Monitoring, like CVP and other static exponents of preload obtained by PICCO (extravascular lung water, global end-diastolic volume index) as well as the dynamic parameters obtained by PiCCO2 (pulse pressure variation, stroke volume variation), was not sensitive enough to describe recipient volume status. The immediate graft function was observed, and after 11 months satisfactory estimated glomerular filtration rate is noted with the absence of donor-specific antibodies.
The history of heart transplantation with existing arteriovenous fistula makes clinical tools such as continuous cardiac output monitoring and CVP parameter inadequate for describing the hemodynamic situation. The high level of panel-reactive antibodies and positive crossmatch possibly caused by IgM antibodies do not have to withdraw the recipient from kidney transplantation.
•Hemodynamic monitoring of a heart recipient under general anesthesia is difficult.•Successful kidney transplantation with positive crossmatch in a heart recipient is possible.•Right heart volume overload may be caused by the presence of arteriovenous fistula.
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