Effect of increasing age and ureteral stent implantation on urinary tract infections after kidney transplantation - update of recent literature.

PURPOSE OF REVIEW: This review aims to present the recent literature regarding effects of aging and ureteral stent implantation (UrS) on the risk of urinary tract infections (UTIs) in kidney transplant (KTX) recipients. RECENT FINDINGS: UTIs in kidney transplant recipients remain a clinical challenge and represent a leading cause of morbidity, hospitalization rates, and mortality. Higher age was described as a significant risk factor for UTIs in several studies including a recent Brazilian analysis, indicating a 3.6%/years of age increase in UTI risk. Subsequently, a large meta-analysis, published in 2023, confirmed the correlation between older age and elevated UTI risk. The Swiss Transplant Cohort Study in 2022, largest of its kind, similarly confirmed a link between advanced age and heightened risk of recurrent UTIs in KTX. A recent prospective study highlighted UrS placement as a modifiable risk factor, emphasizing the need for careful consideration and antibiotic prophylaxis. Additionally, the type of stents played a crucial role, with external stents associated with a 1.69 times higher UTI risk. The challenge of determining optimal UrS removal timing further complicates posttransplant care, with insufficient evidence to guide practices. SUMMARY: The aging population of KTX recipients requires a personalized approach to effectively reduce and manage UTIs as one of the most important complications following KTX. Prophylactic stent implantation is successful in lowering ureteral complications, however, is associated with an increased incidence of UTIs. To reduce the increased risk of UTIs, the length of stent insertion requires strict supervision and maintenance.

Acute Kidney Injury and BK Polyomavirus in Urine Sediment Cells.

Polyomaviruses are widespread, with BK viruses being most common in humans who require immunosuppression due to allotransplantation. Infection with BK polyomavirus (BKV) may manifest as BK virus-associated nephropathy and hemorrhagic cystitis. Established diagnostic methods include the detection of polyomavirus in urine and blood by PCR and in tissue biopsies via immunohistochemistry. In this study, 79 patients with pathological renal retention parameters and acute kidney injury (AKI) were screened for BK polyomavirus replication by RNA extraction, reverse transcription, and virus-specific qPCR in urine sediment cells. A short fragment of the VP2 coding region was the target of qPCR amplification; patients with (n = 31) and without (n = 48) a history of renal transplantation were included. Urine sediment cell immunofluorescence staining for VP1 BK polyomavirus protein was performed using confocal microscopy. In 22 patients with acute renal injury, urinary sediment cells from 11 participants with kidney transplantation (KTX) and from 11 non-kidney transplanted patients (nonKTX) were positive for BK virus replication. BK virus copies were found more frequently in patients with AKI stage III (n = 14). Higher copy numbers were detected in KTX patients having experienced BK polyoma-nephropathy (BKPyVAN) in the past or diagnosed recently by histology (5.6 × 109-3.1 × 1010). One patient developed BK viremia following delayed graft function (DGF) with BK virus-positive urine sediment. In nonKTX patients with BK copies, decoy cells were absent; however, positive staining of cells was found with epithelial morphology. Decoy cells were only found in KTX patients with BKPyVAN. In AKI, damage to the tubular epithelium itself may render the epithelial cells more permissive for polyoma replication. This non-invasive diagnostic approach to assess BK polyomavirus replication in urine sediment cells has the potential to identify KTX patients at risk for viremia and BKPyVAN during AKI. This method might serve as a valuable screening tool for close monitoring and tailored immunosuppression decisions.

Levels of donor-derived cell-free DNA and chemokines in BK polyomavirus-associated nephropathy.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) carries a risk of irreversible allograft injury. While detection of BK viremia and biopsy assessment are the current diagnostic gold standard, the diagnostic value of biomarkers reflecting tissue injury (donor-derived cell-free DNA [dd-cfDNA]) or immune activation (C-X-C motif chemokine ligand [CXCL]9 and CXCL10) remains poorly defined. METHODS: For this retrospective study, 19 cases of BKPyVAN were selected from the Vienna transplant cohort (biopsies performed between 2012 and 2019). Eight patients with T cell-mediated rejection (TCMR), 17 with antibody-mediated rejection (ABMR) and 10 patients without polyomavirus nephropathy or rejection served as controls. Fractions of dd-cfDNA were quantified using next-generation sequencing and CXCL9 and CXCL10 were detected using multiplex immunoassays. RESULTS: BKPyVAN was associated with a slight increase in dd-cfDNA (median; interquartile range: .38% [.27%-1.2%] vs. .21% [.12%-.34%] in non-rejecting control patients; p = .005). Levels were far lower than in ABMR (1.2% [.82%-2.5%]; p = .004]), but not different from TCMR (.54% [.26%-3.56%]; p = .52). Within the BKPyVAN cohort, we found no relationship between dd-cfDNA levels and the extent of tubulo-interstitial infiltrates, BKPyVAN class and BK viremia/viruria, respectively. In some contrast to dd-cfDNA, concentrations of urinary CXCL9 and CXCL10 exceeded those detected in ABMR, but similar increases were also found in TCMR. CONCLUSION: BKPyVAN can induce moderate increases in dd-cfDNA and concomitant high urinary excretion of chemokines, but this pattern may be indistinguishable from that of TCMR. Our results argue against a significant value of these biomarkers to reliably distinguish BKPyVAN from rejection.

Diagnostic value of donor-derived cell-free DNA to predict antibody-mediated rejection in donor-specific antibody-positive renal allograft recipients.

Circulating donor-specific antibodies (DSA) do not necessarily indicate antibody-mediated rejection (ABMR). Here, we evaluated the diagnostic value of donor-derived cell-free DNA (dd-cfDNA) as an add-on to DSA detection. The study included two independent cohorts of DSA+ kidney allograft recipients, 45 subclinical cases identified by cross-sectional antibody screening (cohort 1), and 30 recipients subjected to indication biopsies (cohort 2). About 50% of the DSA+ recipients had ABMR and displayed higher dd-cfDNA levels than DSA+ ABMR- recipients (cohort 1: 1.90% [median; IQR: 0.78-3.90%] vs. 0.52% [0.35-0.72%]; P < 0.001); (cohort 2: 1.20% [0.82-2.50%] vs. 0.59% [0.28-2.05%]; P = 0.086). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.89 and 0.69 for dd-cfDNA, and 0.88 and 0.77 for DSA mean fluorescence intensity (MFI), respectively. In combined models, adding dd-cfDNA to DSA-MFI or vice versa significantly improved the diagnostic accuracy. Limited diagnostic performance of dd-cfDNA in cohort 2 was related to the frequent finding of other types of graft injury among ABMR- recipients, like T cell-mediated rejection or glomerulonephritis. For dd-cfDNA in relation to injury of any cause an AUC of 0.97 was calculated. Monitoring of dd-cfDNA in DSA+ patients may be a useful tool to detect ABMR and other types of injury.

Markers of potassium homeostasis in salt losing tubulopathies- associations with hyperaldosteronism and hypomagnesemia.

BACKGROUND: Renal loss of potassium (K+) and magnesium (Mg2+) in salt losing tubulopathies (SLT) leads to significantly reduced Quality of Life (QoL) and higher risks of cardiac arrhythmia. The normalization of K+ is currently the most widely accepted treatment target, however in even excellently designed RCTs the increase of K+ was only mild and rarely normalized. These findings question the role of K+ as the ideal marker of potassium homeostasis in SLT. Aim of this hypothesis-generating study was to define surrogate endpoints for future treatment trials in SLT in terms of their usefulness to determine QoL and important clinical outcomes. METHODS: Within this prospective cross-sectional study including 11 patients with SLTs we assessed the biochemical, clinical and cardiological parameters and their relationship with QoL (RAND SF-36). The primary hypothesis was that QoL would be more dependent of higher aldosterone concentration, assessed by the transtubular-potassium-gradient (TTKG). Correlations were evaluated using Pearson's correlation coefficient. RESULTS: Included patients were mainly female (82%, mean age 34 ± 12 years). Serum K+ and Mg2+ was 3.3 ± 0.6 mmol/l and 0.7 ± 0.1 mmol/l (mean ± SD). TTKG was 9.5/3.4-20.2 (median/range). While dimensions of mental health mostly correlated with serum Mg2+ (r = 0.68, p = 0.04) and K+ (r = 0.55, p = 0.08), better physical health was associated with lower aldosterone levels (r = -0.61, p = 0.06). TTKG was neither associated with aldosterone levels nor with QoL parameters. No relevant abnormalities were observed in neither 24 h-ECG nor echocardiography. CONCLUSIONS: Hyperaldosteronism, K+ and Mg2+ were the most important parameters of QoL. TTKG was no suitable marker for hyperaldosteronism or QoL. Future confirmatory studies in SLT should assess QoL as well as aldosterone, K+ and Mg2+.

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 µmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 µmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.

High seroprevalence of anti-Hepatitis E antibodies in Austrian patients with autoimmune hepatitis.

BACKGROUND & AIMS: Increasing numbers of autochthonous hepatitis E virus infections have been reported in Europe. Chronic infections have been shown in immune-compromised patients after solid organ transplantation. Hepatitis E virus might be a possible trigger for autoimmune hepatitis and might cause disease flares or relapses in the further course of disease. Aim of this study was to investigate the presence of hepatitis E virus antibodies and hepatitis E virus RNA, and to analyse their impact on immunosuppressive treatment in patients with autoimmune hepatitis. METHODS: Sera from 92 autoimmune hepatitis patients (73/79.3% female, age: 42.2 ± 16.3 years [mean ± SD]) were tested. Patients were scored according to the simplified and revised scoring systems of the International Autoimmune Hepatitis Group. The prevalence of anti- hepatitis E virus antibodies (Beijing Wantai Biological Pharmacy Enterprises Co., Ltd, Beijing, China) and hepatitis E virus RNA was determined. RESULTS: 19/20.7% autoimmune hepatitis patients tested positive for hepatitis E virus-IgG, which was higher than in previous reports of healthy Austrian individuals (12.4%, P = 0.031); hepatitis E virus RNA was not detectable in any patient. Anti-hepatitis E virus positive patients were older (49.5 ± 9.5 vs 40.4 ± 17.2 years [mean ± SD], P = 0.033) but did not differ in laboratory findings at diagnosis (AST: 14.6 [1.3-70.6] vs 9.5 [0.7-62.7] × ULN [median/range]; P = 0.387, alanine aminotransferase: 18.3 [1.6-62.7] vs. 12.9 [0.8-62.6] × ULN; P = 0.511; IgG: 1.4 [1.0-2.5] vs 1.3 [0.6-3.8] g/dL × ULN; P = 0.278) nor in alanine aminotransferase levels after six months (0.7 [0.5-2.4] vs 1.0 U/L × ULN [0.1-22.4]; P = 0.077). CONCLUSIONS: No chronic hepatitis E virus infection was observed in our cohort of autoimmune hepatitis patients. Anti- hepatitis E virus-IgG positive patients were older and the seroprevalence was nearly twice as high as reported previously in healthy Austrian individuals, suggesting that hepatitis E virus-infection might act as trigger for the development of autoimmune hepatitis.

An integrative approach for the assessment of peritubular capillaritis extent and score in low-grade microvascular inflammation-associations with transplant glomerulopathy and graft loss.

Background: Peritubular capillaritis (ptc), reported by the ptc score, is a major feature of kidney allograft rejection and microvascular inflammation (MVI). MVI sum scores (ptc + glomerulitis score ≥2) are accepted diagnostic surrogates of human leucocyte antigen (HLA)-antibody interaction. However, low-grade inflammation is common and ptc scores (number of leucocytes/capillary) may not mirror all aspects of ptc morphology. Recently we observed a relationship of the diffuse extent of ptc (inflammation of >50% of the renal cortex) with graft loss and significantly higher donor-specific antibody levels, suggesting potential inclusion of diffuse ptc as an additional surrogate of antibody-antigen interaction. Methods: We sought to assess how a combination of ptc score and extent in low-grade inflammation (ptc1) affects transplant glomerulopathy (TG) and graft loss risk. Patients (n = 616) were assessed for MVI in first indication biopsies. Cases with a ptc score of 1 but diffuse extent (ptc1diffuse, g-score = 0, n = 26) were considered additional surrogates of HLA-antibody interaction and compared with MVI ≥2 and MVI <2. Results: The ptc1diffuse and MVI score ≥2 subjects had worse graft survival (42% and 59%) compared with an MVI score <2 (70%) (P = 0.002). The incorporation of ptc1diffuse in the MVI score ≥2 increased the receiver operating characteristics curve for TG [area under the curve (AUC) 0.602; P = 0.008] compared with a Banff MVI score ≥2 (AUC 0.56; P = 0.12); cases with baseline TG were excluded. In multivariate analysis, ptc1diffuse remained independently related to TG (odds ratio 3.89; P = 0.008) and graft loss (hazard ratio 2.64; P = 0.001) even after inclusion of all rejection episodes. Conclusion: An integrated view of ptc morphology including diffuse ptc in MVI is superior for TG and graft loss risk assessment.

Next generation sequencing based assessment of the alloreactive T cell receptor repertoire in kidney transplant patients during rejection: a prospective cohort study.

BACKGROUND: Kidney transplantation is the optimal treatment in end stage renal disease but the allograft survival is still hampered by immune reactions against the allograft. This process is driven by the recognition of allogenic antigens presented to T-cells and their unique T-cell receptor (TCR) via the major histocompatibility complex (MHC), which triggers a complex immune response potentially leading to graft injury. Although the immune system and kidney transplantation have been studied extensively, the subtlety of alloreactive immune responses has impeded sensitive detection at an early stage. Next generation sequencing of the TCR enables us to monitor alloreactive T-cell populations and might thus allow the detection of early rejection events. METHODS/DESIGN: This is a prospective cohort study designed to sequentially evaluate the alloreactive T cell repertoire after kidney transplantation. The TCR repertoire of patients who developed biopsy confirmed acute T cell mediated rejection (TCMR) will be compared to patients without rejection. To track the alloreactive subsets we will perform a mixed lymphocyte reaction between kidney donor and recipient before transplantation and define the alloreactive TCR repertoire by next generation sequencing of the complementary determining region 3 (CDR3) of the T cell receptor beta chain. After initial clonotype assembly from sequencing reads, TCR repertoire diversity and clonal expansion of T cells of kidney transplant recipients in periphery and kidney biopsy will be analyzed for changes after transplantation, during, prior or after a rejection. The goal of this study is to describe changes of overall T cell repertoire diversity, clonality in kidney transplant recipients, define and track alloreactive T cells in the posttransplant course and decipher patterns of expanded alloreactive T cells in acute cellular rejection to find an alternative monitoring to invasive and delayed diagnostic procedures. DISCUSSION: Changes of the T cell repertoire and tracking of alloreactive T cell clones after combined bone marrow and kidney transplant has proven to be of potential use to monitor the donor directed alloresponse. The dynamics of the donor specific T cells in regular kidney transplant recipients in rejection still rests elusive and can give further insights in human alloresponse. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03422224 , registered February 5th 2018.

An analytical performance approach for RCS/RS with one robot serving multiple stack heights under a one-path relocation strategy.

Robotic compact storage and retrieval systems (RCS/RS) represent a modern and useful storage system since the number of installed systems is growing fast. The modularity and demand-based scalability are reasons, therefore. Nonetheless, there are hardly any statements on the performance of those warehouses. This paper presents an analytical calculation approach to determine the performance of an RCS/RS with one operating robot serving different grid sizes and a varying number of stacked containers. The robot's cycle time is calculated by assuming a uniform distribution of container stacks and a probabilistic storage height. A discrete-event simulation model of an RCS/RS is built to verify and validate the analytical approximations. The system's basic structure and the input parameters originate from a European material handling provider. After the verification and validation, an extensive parameter variation is done with the target of displaying a wide range of usage. This analytical approach, which is easy and fast solvable with standard calculation programs, represents an easy and fast tool to predict the performance of one robot operating in an RCS/RS for any system configuration.

Accuracy of robotic radiosurgery in renal cell carcinoma.

PURPOSE: Although emerging clinical evidence supports robotic radiosurgery as a highly effective treatment option for renal cell carcinoma (RCC) less than 4 cm in diameter, delivery uncertainties and associated target volume margins have not been studied in detail. We assess intrafraction tumor motion patterns and accuracy of robotic radiosurgery in renal tumors with real-time respiratory tracking to optimize treatment margins. METHODS: Delivery log files from 165 consecutive treatments of RCC were retrospectively analyzed. Five components were considered for planning target volume (PTV) margin estimation: (a) The model error from the correlation model between patient breath and tumor motion, (b) the prediction error from an algorithm predicting the patient breathing pattern, (c) the targeting error from the treatment robot, (d) the inherent total accuracy of the system for respiratory motion tracking, and (e) the margin required to cover potential target rotation, simulated with PTV rotations up to 10°. RESULTS: The median tumor motion was 10.5 mm, 2.4 mm and 4.4 mm in the superior-inferior, left-right, and anterior-posterior directions, respectively. The root of the sum of squares of all contributions to the system's inaccuracy results in a minimum PTV margin of 4.3 mm, 2.6 mm and 3.0 mm in the superior-inferior, left-right and anterior-posterior directions, respectively, assuming optimal fiducial position and neglecting target deformation. CONCLUSIONS: We have assessed kidney motion and derived PTV margins for the treatment of RCC with robotic radiosurgery, which helps to deliver renal treatments in a more consistent manner and potentially further improve outcomes.

The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation.

BK polyomavirus (BKPyV) remains a significant challenge after kidney transplantation. International experts reviewed current evidence and updated recommendations according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Risk factors for BKPyV-DNAemia and biopsy-proven BKPyV-nephropathy include recipient older age, male sex, donor BKPyV-viruria, BKPyV-seropositive donor/-seronegative recipient, tacrolimus, acute rejection, and higher steroid exposure. To facilitate early intervention with limited allograft damage, all kidney transplant recipients should be screened monthly for plasma BKPyV-DNAemia loads until month 9, then every 3 mo until 2 y posttransplant (3 y for children). In resource-limited settings, urine cytology screening at similar time points can exclude BKPyV-nephropathy, and testing for plasma BKPyV-DNAemia when decoy cells are detectable. For patients with BKPyV-DNAemia loads persisting >1000 copies/mL, or exceeding 10 000 copies/mL (or equivalent), or with biopsy-proven BKPyV-nephropathy, immunosuppression should be reduced according to predefined steps targeting antiproliferative drugs, calcineurin inhibitors, or both. In adults without graft dysfunction, kidney allograft biopsy is not required unless the immunological risk is high. For children with persisting BKPyV-DNAemia, allograft biopsy may be considered even without graft dysfunction. Allograft biopsies should be interpreted in the context of all clinical and laboratory findings, including plasma BKPyV-DNAemia. Immunohistochemistry is preferred for diagnosing biopsy-proven BKPyV-nephropathy. Routine screening using the proposed strategies is cost-effective, improves clinical outcomes and quality of life. Kidney retransplantation subsequent to BKPyV-nephropathy is feasible in otherwise eligible recipients if BKPyV-DNAemia is undetectable; routine graft nephrectomy is not recommended. Current studies do not support the usage of leflunomide, cidofovir, quinolones, or IVIGs. Patients considered for experimental treatments (antivirals, vaccines, neutralizing antibodies, and adoptive T cells) should be enrolled in clinical trials.

Magnetic resonance elastography resolving all gross anatomical segments of the kidney during controlled hydration.

Introduction: Magnetic resonance elastography (MRE) is a non-invasive method to quantify biomechanical properties of human tissues. It has potential in diagnosis and monitoring of kidney disease, if established in clinical practice. The interplay of flow and volume changes in renal vessels, tubule, urinary collection system and interstitium is complex, but physiological ranges of in vivo viscoelastic properties during fasting and hydration have never been investigated in all gross anatomical segments simultaneously. Method: Ten healthy volunteers underwent two imaging sessions, one following a 12-hour fasting period and the second after a drinking challenge of >10 mL per kg body weight (60-75 min before the second examination). High-resolution renal MRE was performed using a novel driver with rotating eccentric mass placed at the posterior-lateral wall to couple waves (50 Hz) to the kidney. The biomechanical parameters, shear wave speed (cs in m/s), storage modulus (Gd in kPa), loss modulus (Gl in kPa), phase angle (Υ=2πatanGlGd) and attenuation (α in 1/mm) were derived. Accurate separation of gross anatomical segments was applied in post-processing (whole kidney, cortex, medulla, sinus, vessel). Results: High-quality shear waves coupled into all gross anatomical segments of the kidney (mean shear wave displacement: 163 ± 47 µm, mean contamination of second upper harmonics <23%, curl/divergence: 4.3 ± 0.8). Regardless of the hydration state, median Gd of the cortex and medulla (0.68 ± 0.11 kPa) was significantly higher than that of the sinus and vessels (0.48 ± 0.06 kPa), and consistently, significant differences were found in cs, Υ, and Gl (all p < 0.001). The viscoelastic parameters of cortex and medulla were not significantly different. After hydration sinus exhibited a small but significant reduction in median Gd by -0.02 ± 0.04 kPa (p = 0.01), and, consequently, the cortico-sinusoidal-difference in Gd increased by 0.04 ± 0.07 kPa (p = 0.05). Only upon hydration, the attenuation in vessels became lower (0.084 ± 0.013 1/mm) and differed significantly from the whole kidney (0.095 ± 0.007 1/mm, p = 0.01). Conclusion: High-resolution renal MRE with an innovative driver and well-defined 3D segmentation can resolve all renal segments, especially when including the sinus in the analysis. Even after a prolonged hydration period the approach is sensitive to small hydration-related changes in the sinus and in the cortico-sinusoidal-difference.

Polyomavirus Nephropathy in ABO Blood Group-Incompatible Kidney Transplantation: Torque Teno Virus and Immunosuppressive Burden as an Approximation to the Problem.

Introduction: Earlier reports suggest that patients after ABO-incompatible kidney transplantation (ABOi) are at enhanced risk of developing BK-virus (BKV, also known as BK polyomavirus [BKPyV]) nephropathy (BKPyVAN). It remains elusive whether this is a result of more intense immunosuppression or an ABOi-associated "intrinsic attribute." To address this question, we measured Torque Teno virus (TTV) loads as a quantitative proxy for immunosuppressive depth in ABOi recipients and compared them to human leukocyte antigen-incompatible (HLAi, i.e. pretransplant donor-specific antibody-positive) and standard-risk transplant recipients. Methods: Our retrospective study screened 2256 consecutive kidney transplantations performed between 2007 and 2020 at the Medical University of Vienna. Out of 629 in-principle eligible transplantations, we were able to include 465 patients: 42 ABOi, 106 HLAi, and 317 control recipients. Longitudinal TTV- polymerase chain reaction (PCR) and BKV-PCR was carried out at predefined timepoints and ranged from pretransplant until month 24 posttransplantation. TTV loads and immunosuppression were evaluated in the context of BKV-associated complications. Results: ABOi recipients had a higher TTV load compared to HLAi and controls both at month 3 (median 1.5 × 109 vs. 2.4 × 108 vs. 9.1 × 107; P = 0.010) and at month 6 (3.1 × 109 vs. 1.4 × 107 vs. 6.4 × 107; P = 0.014) posttransplantation. Tacrolimus exposure was significantly higher in ABOi patients compared to HLAi and control patients (ABOi vs. HLAi: P = 0.007; ABOi vs. controls: P < 0.0001). Biopsy-proven BKPyVAN was more frequent in ABOi recipients when compared to HLAi and control recipients (11.9% vs. 2.8% vs. 4.1%; P = 0.046). Conclusion: Our data support the assumption that ABOi patients are indeed at higher risk to develop BKPyVAN. A higher TTV load and immunosuppressive burden suggest that intense immunosuppression, rather than an "intrinsic attribute" conferred by ABOi, may contribute to this finding.

Diverse types of knowledge on a plate: a multi-perspective and multi-method approach for the transformation of urban food systems towards sustainable diets.

Urbanization processes are accompanied by growing global challenges for food systems. Urban actors are increasingly striving to address these challenges through a focus on sustainable diets. However, transforming food systems towards more sustainable diets is challenging and it is unclear what the local scope of action might be. Co-production of knowledge between science and non-science is particularly useful for analysing context-specific solutions and promise to result in more robust socio-economic, political and technical solutions. Thus, this paper aims to integrate different types and sources of knowledge to understand urban food systems transformation towards a more sustainable diet in Vienna; and, second, to analyse and reflect on the difficulties and ways forward to integrate diverse actors' perspectives, multiple methods and epistemologies. We created different future scenarios that illustrate the synergies and trade-offs of various bundles of measures and the interactions among single dimensions of sustainable diets. These scenarios show that there is plenty of scope for local action, but co-ordination across diverse groups, interests, and types of knowledge is necessary to overcome lock-ins.

Lessons from Polyomavirus Immunofluorescence Staining of Urinary Decoy Cells.

Decoy cells that can be detected in the urine sediment of immunosuppressed patients are often caused by the uncontrolled replication of polyomaviruses, such as BK-Virus (BKV) and John Cunningham (JC)-Virus (JCV), within the upper urinary tract. Due to the wide availability of highly sensitive BKV and JCV PCR, the diagnostic utility of screening for decoy cells in urine as an indicator of polyomavirus-associated nephropathy (PyVAN) has been questioned by some institutions. We hypothesize that specific staining of different infection time-dependent BKV-specific antigens in urine sediment could allow cell-specific mapping of antigen expression during decoy cell development. Urine sediment cells from six kidney transplant recipients (five males, one female) were stained for the presence of the early BKV gene transcript lTag and the major viral capsid protein VP1 using monospecific antibodies, monoclonal antibodies and confocal microscopy. For this purpose, cyto-preparations were prepared and the BK polyoma genotype was determined by sequencing the PCR-amplified coding region of the VP1 protein. lTag staining began at specific sites in the nucleus and spread across the nucleus in a cobweb-like pattern as the size of the nucleus increased. It spread into the cytosol as soon as the nuclear membrane was fragmented or dissolved, as in apoptosis or in the metaphase of the cell cycle. In comparison, we observed that VP1 staining started in the nuclear region and accumulated at the nuclear edge in 6-32% of VP1+ cells. The staining traveled through the cytosol of the proximal tubule cell and reached high intensities at the cytosol before spreading to the surrounding area in the form of exosome-like particles. The spreading virus-containing particles adhered to surrounding cells, including erythrocytes. VP1-positive proximal tubule cells contain apoptotic bodies, with 68-94% of them losing parts of their DNA and exhibiting membrane damage, appearing as "ghost cells" but still VP1+. Specific polyoma staining of urine sediment cells can help determine and enumerate exfoliation of BKV-positive cells based on VP1 staining, which exceeds single-face decoy staining in terms of accuracy. Furthermore, our staining approaches might serve as an early readout in primary diagnostics and for the evaluation of treatment responses in the setting of reduced immunosuppression.

Self-Shielding Gyroscopic Radiosurgery-A First Clinical Experience, Case Series, and Dosimetric Comparison.

BACKGROUND: Self-shielding gyroscopic radiosurgery (GRS) represents a technical innovation in the field of stereotactic radiosurgery. GRS does not require a radiation vault and is optimized for radiosurgical treatments. Reports on its usage are limited. We describe the first clinical experience of GRS at our institution to assess the application of GRS in the treatment of cranial tumors. Moreover, we perform a dosimetric comparison to robotic radiosurgery (RRS) with vestibular schwannoma (VS) GRS patients. METHODS: Patients who were treated with GRS between July and November 2021 were included. Patient, tumor, and dosimetric characteristics were retrospectively summarized and analyzed. RESULTS: Forty-one patients with 48 intracranial tumors were included. Tumor entities mostly comprised VS, brain metastases, and meningiomas. The median prescription dose and isodose line were 13.5 Gy and 50.0% for benign neoplasia versus 20 Gy and 60.0% for malignant tumors, respectively. The mean planning target volume was 1.5 cubic centimeters. All patients received a single-fraction treatment without encountering any technical setup difficulties. Treatment plan comparisons with RRS revealed comparable plan characteristics, dose gradients, and organs at risk doses. Significant differences were detected concerning the new conformity index and number of monitor units per treatment (both P < 0.01). CONCLUSIONS: This case series provides more evidence on the usage of self-shielding GRS in the management of cranial tumors. Dosimetric comparisons for VS cases revealed mostly equivalent dosimetric characteristics to RRS. Further clinical and physical analyses for GRS are underway.

Single-isocenter stereotactic radiosurgery for multiple brain metastases: Impact of patient misalignments on target coverage in non-coplanar treatments.

Frameless single-isocenter non-coplanar stereotactic radiosurgery (SRS) for patients with multiple brain metastases is a treatment at high geometrical complexity. The goal of this study is to analyze the dosimetric impact of non-coplanar image guidance with stereoscopic X-ray imaging. Such an analysis is meant to provide insights on the adequacy of safety margins, and to evaluate the benefit of imaging at non-coplanar configurations. The ExacTrac® (ET) system (Brainlab AG, Munich, Germany) was used for stereoscopic X-ray imaging in frameless single-isocenter non-coplanar SRS for multiple brain metastases. Sub-millimeter precision was found for the ET-based pre-treatment setup, whereas a degradation was noted for non-coplanar treatment angles. Misalignments without intra-fractional positioning corrections were reconstructed in 6 degrees of freedom (DoF) to resemble the situation without non-coplanar image guidance. Dose recalculation in 20 SRS patients with applied positioning corrections did not reveal any significant differences in D98% for 75 planning target volumes (PTVs) and gross tumor volumes (GTVs). For recalculation without applied positioning corrections, significant differences (p<0.05) were reported in D98% for both PTVs and GTVs, with stronger effects for small PTV volumes. A worst-case analysis at increasing translational and rotational misalignment revealed that dosimetric changes are a complex function of the combination thereof. This study highlighted the important role of positioning correction with ET at non-coplanar configurations in frameless single-isocenter non-coplanar SRS for patients with multiple brain metastases. Uncorrected patient misalignments at non-coplanar couch angles were linked to a significant loss of PTV coverage, with effects varying according to the combination of single DoF and PTV geometrical properties.

Eculizumab use in a tertiary care nephrology center: data from the Vienna TMA cohort.

BACKGROUND: Practice patterns of eculizumab use are not well described. We examined indications for, and outcomes of, eculizumab therapy in a tertiary care nephrology center. METHODS: We used the "Vienna TMA cohort" and the hospital pharmacy database at the Medical University of Vienna to identify patients that received eculizumab treatment between 2012 and 2019. We describe clinical characteristics, details of eculizumab use, and outcomes of patients with complement gene-variant mediated TMA (cTMA), secondary TMA (sTMA) and C3 glomerulopathy (C3G). RESULTS: As of December 2019, 23 patients received complement blockade at the Division of Nephrology and Dialysis: 15 patients were diagnosed with cTMA, 6 patients with sTMA and 2 patients with C3G. Causes of sTMA were bone marrow transplantation (n = 2), malignant hypertension, malignant tumor, systemic lupus erythematosus, antiphospholipid syndrome and lung transplantation (each n = 1). Across all indications, patients had a median age of 31 and were predominantly female (78%) and the median duration of treatment was 227 days. Hematological recovery was seen in most patients, while renal response was best in patients with cTMA. Adverse events were recorded in 26%. CONCLUSIONS: In summary, eculizumab is the treatment of choice for cTMA patients that do not respond to plasma therapy. In patients with sTMA and C3G, the response rates to therapy are much lower and therefore, the decision to start therapy needs to be considered carefully.

Three-Month Follow-Up of Heterologous vs. Homologous Third SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Secondary Analysis of a Randomized Controlled Trial.

Response to SARS-CoV-2-vaccines in kidney-transplant recipients (KTR) is severely reduced. Heterologous3rd vaccination combining mRNA and vector vaccines did not increase seroconversion at 4 weeks after vaccination, but evolution of antibody levels beyond the first month remains unknown. We have recently completed a randomized-controlled trial on heterologous (Ad26COVS1) vs. homologous (BNT162b2 or mRNA-1273) 3rd vaccination in 201 KTR not developing SARS-CoV-2-spike-protein antibodies following two doses of mRNA vaccine (EurdraCT: 2021-002927-39). Here, we report seroconversion at the second follow-up at 3 months after the 3rd vaccination (prespecified secondary endpoint). In addition, higher cut-off levels associated with neutralizing capacity and protective immunity were applied (i.e., > 15, > 100, > 141, and > 264 BAU/ml). A total of 169 patients were available for the 3-month follow-up. Overall, seroconversion at 3 months was similar between both groups (45 vs. 50% for mRNA and the vector group, respectively; p = 0.539). However, when applying higher cut-off levels, a significantly larger number of individuals in the vector group reached antibody levels > 141 and > 264 BAU/ml at the 3-month follow-up (141 BAU/ml: 4 vs. 15%, p = 0.009 and 264 BAU/ml: 1 vs. 10%, p = 0.018 for mRNA vs. the vector vaccine group, respectively). In line, antibody levels in seroconverted patients further increased from month 1 to month 3 in the vector group while remaining unchanged in the mRNA group (median increase: mRNA = 1.35 U/ml and vector = 27.6 U/ml, p = 0.004). Despite a similar overall seroconversion rate at 3 months following 3rd vaccination in KTR, a heterologous 3rd booster vaccination with Ad26COVS1 resulted in significantly higher antibody levels in responders.