Population-wide persistent hemostatic changes after vaccination with ChAdOx1-S

Various vaccines were developed to reduce the spread of the Severe Acute Respiratory Syndrome Cov-2 (SARS-CoV-2) virus. Quickly after the start of vaccination, reports emerged that anti-SARS-CoV-2 vaccines, including ChAdOx1-S, could be associated with an increased risk of thrombosis. We investigated the hemostatic changes after ChAdOx1-S vaccination in 631 health care workers. Blood samples were collected 32 days on average after the second ChAdOx1-S vaccination, to evaluate hemostatic markers such as D-dimer, fibrinogen, α2-macroglobulin, FVIII and thrombin generation. Endothelial function was assessed by measuring Von Willebrand Factor (VWF) and active VWF. IL-6 and IL-10 were measured to study the activation of the immune system. Additionally, SARS-CoV-2 anti-nucleoside and anti-spike protein antibody titers were determined. Prothrombin and fibrinogen levels were significantly reduced after vaccination (−7.5% and −16.9%, p < 0.0001). Significantly more vaccinated subjects were outside the normal range compared to controls for prothrombin (42.1% vs. 26.4%, p = 0.026) and antithrombin (23.9% vs. 3.6%, p = 0.0010). Thrombin generation indicated a more procoagulant profile, characterized by a significantly shortened lag time (−11.3%, p < 0.0001) and time-to-peak (−13.0% and p < 0.0001) and an increased peak height (32.6%, p = 0.0015) in vaccinated subjects compared to unvaccinated controls. Increased VWF (+39.5%, p < 0.0001) and active VWF levels (+24.1 %, p < 0.0001) pointed toward endothelial activation, and IL-10 levels were significantly increased (9.29 pg/mL vs. 2.43 pg/mL, p = 0.032). The persistent increase of IL-10 indicates that the immune system remains active after ChAdOx1-S vaccination. This could trigger a pathophysiological mechanism causing an increased thrombin generation profile and vascular endothelial activation, which could subsequently result in and increased risk of thrombotic events

Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe:Findings from the ERA Registry

Background and hypothesis: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death.Methods: We used data from the European Renal Association (ERA) Registry on 69,854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival.Results: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%).Conclusion: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach

Ischemia in kidney transplantation: clinical risk factor and epigenetic modifier

Organ transplantation has become the treatment of choice for patients with organ failure. Novel and potent immunosuppressive drugs have become available, and have significantly reduced the incidence of acute rejection and improved short term organ survival. However, long-term graft survival hasn’t improved in parallel over the past decades and it is well established that ongoing destruction of the transplant by the recipient’s immune system continues to be a major contributor to graft loss. Immunosuppressants only provide aspecific suppression of the immune system and are also associated with significant side effects, among others damage of the renal transplant. Therefore, there is a continuing interest in transplantation without the need of long-term immunosuppression (or induction of transplantation tolerance) by using regulatory immune cells or influencing tolerogenic molecular pathways. In the last decade, several regulatory cell populations and tolerogenic pathways have been identified in murine models. In this project, we will describe the changes in immune cells and immune gene expression within the allograft using innovative techniques in a longitudinal manner, and the results will be correlated with changes seen in the peripheral blood and patient outcome. This will identify the relevant regulatory immune cell populations in organ transplantation and help us designing future tolerance-inducing studies in patients suffering from organ failure.status: publishe

De (nog) niet bemiddelbaren: een verloren groep op de Antwerpse arbeidsmarkt?

Een onderzoek in opdracht van vzw Werk en Economie van de stad Antwerpen in het kader van het samenwerkingsverband stad Antwerpen – OCMW-Antwerpen – VDAB. Wat verhindert langdurig werkzoekenden en leefloners om terug aan het werk te gaan? Deze vraag dringt zich des te meer op naarmate het activeringsbeleid stoot op een harde kern van ‘moeilijk of (nog) niet bemiddelbaren’. Dit onderzoek voor de stad Antwerpen brengt de uiteenlopende belemmeringen voor activering systematisch in kaart. Hiervoor maken we gebruik van de door consulenten geregistreerde ‘zachte kenmerken’ zoals motivatie, zelfvertrouwen, gezondheid en zorgtaken. Deze gegevens reiken de sleutel aan om tot een omvattende aanpak (het zogenoemde ‘sluitend maatpak’) te komen voor de (nog) niet bemiddelbaren.nrpages: 134status: publishe

The Emerging Role of DNA Methylation in Kidney Transplantation: A Perspective

Allograft outcome depends on a range of factors, including donor age, the allo-immune response, ischemia-reperfusion injury, and interstitial fibrosis of the allograft. Changes in the epigenome, and in DNA methylation in particular, have been implicated in each of these processes, in either the kidney or other organ systems. This review provides a primer for DNA methylation analyses and a discussion of the strengths and weaknesses of current studies, but it is also a perspective for future DNA methylation research in kidney transplantation. We present exciting prospects for leveraging DNA methylation analyses as a tool in kidney biology research, and as a diagnostic or prognostic marker for predicting allograft quality and success. Topics discussed include DNA methylation changes in aging and in response to hypoxia and oxidative stress upon ischemia-reperfusion injury. Moreover, emerging evidence suggests that DNA methylation contributes to organ fibrosis and that systemic DNA methylation alterations correlate with the rate of kidney function decline in patients with chronic kidney disease and end-stage renal failure. Monitoring or targeting the epigenome could therefore reveal novel therapeutic approaches in transplantation and open up paths to biomarker discovery and targeted therapy.status: publishe

Anastomosis time as risk factor for kidney transplant outcome: more pieces to the puzzle

We read with great interest the article by Weissenbacher and co-workers, showing that anastomosis time adversely impacts kidney transplant outcome(1). Surprisingly, the effect of anastomosis time has been poorly investigated in the past. This stands in stark contrast with the well known fact that warm ischemia - inevitably occurring during this period - has major deleterious impact on tissue viability in general. Previous studies evaluating the effect of anastomosis time focused on delayed graft function, not on other endpoints(2, 3). Therefore, the current study brings new information on this virtually unexplored topic. However, several questions remain unanswered. This article is protected by copyright. All rights reserved.status: publishe

The impact of anastomosis time during kidney transplantation on graft loss: A Eurotransplant cohort study

Recent studies raise the concern that warm ischemia during the time to complete the vascular anastomoses in kidney implantation harms the transplant, but its precise impact on outcome and its interaction with other risk factors remain to be established. We investigated the relationship between anastomosis time and graft survival at 5 years after transplantation in 13964 recipients of solitary deceased-donor kidney transplants in the Eurotransplant region. Anastomosis time was independently associated with graft loss after adjusting for other risk factors (adjusted hazard rate 1.10 for every ten-minute increase, 95% confidence interval 1.06-1.14; P<0.0001), while it did not influence recipient survival (hazard rate 1.00, 95% confidence interval 0.97-1.02). Circulatory-dead donor (DCD) kidneys were less tolerant to prolonged anastomosis time than brain-dead donor kidneys (P for interaction=0.02). The additive effect of anastomosis time with donor warm ischemia time explains this observation, since DCD status was no longer associated with graft survival when adjusted for this sum warm ischemia time and there was no interaction between DCD status and sum warm ischemia time. Thus, the time to create the vascular anastomoses in kidney transplantation is associated with inferior transplant outcome, especially in recipients of DCD kidneys. This article is protected by copyright. All rights reserved.status: publishe

Hospital-Wide SARS-CoV-2 Antibody Screening in 3056 Staff in a Tertiary Center in Belgium

status: publishe

AGING IS ASSOCIATED WITH EPIGENETIC CHANGES IN GENES INVOLVED IN RENAL FIBROSIS: AN EPIGENOME-WIDE ASSOCIATION STUDY

status: publishe

Age-related changes in DNA methylation affect renal histology and post-transplant fibrosis

During ageing, kidney function decreases due to renal tubular atrophy, interstitial fibrosis, glomerulosclerosis and arteriosclerosis. Recently, changes in DNA methylation were shown to contribute to various ageing processes. However, it is unknown whether such changes also contribute to age-related kidney dysfunction. To assess this, we profiled genome-wide changes in DNA methylation (over 800 000 CpG sites) in 95 renal biopsies obtained prior to kidney transplantation from donors aged 16 to 73 years. Donor age significantly associated with the methylation of 92 778 CpGs (false discovery rate under 0.05), corresponding to 10 285 differentially methylated regions. These regions were most frequently located in genes involved in the Wnt/beta-catenin signaling pathway. Using an independent cohort of 67 biopsies, we autonomously validated these findings. Interestingly, the methylation status of these 92 778 age-related CpGs was associated with glomerulosclerosis (34.4% of CpGs at a false discovery rate under 0.05) and interstitial fibrosis (0.9%) and graft function at one year after transplantation, but not with tubular atrophy and arteriosclerosis. No association was observed with any of these pathologies at the time of transplantation (0% at a false discovery rate under 0.05). Thus, age-associated changes in DNA methylation at the time of transplantation predict future injury of transplanted kidneys. Specifically, our epigenome-wide association study demonstrates that epigenetic renal ageing is implicated in progressive fibrosis in both the glomerulus and the interstitium.status: publishe