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"Reuter, Stefan"
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Nanomechanics of the Endothelial Glycocalyx in Experimental Sepsis
The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal side of the endothelium, regulates vascular adhesiveness and permeability. Although central to the pathophysiology of vascular barrier dysfunction in sepsis, glycocalyx damage has been generally understudied, in part because of the aberrancy of in vitro preparations and its degradation during tissue handling. The aim of this study was to analyze inflammation-induced damage of the eGC on living endothelial cells by atomic-force microscopy (AFM) nanoindentation technique. AFM revealed the existence of a mature eGC on the luminal endothelial surface of freshly isolated rodent aorta preparations ex vivo, as well as on cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM detected a marked reduction in glycocalyx thickness (266 ± 12 vs. 137 ± 17 nm, P<0.0001) and stiffness (0.34 ± 0.03 vs. 0.21 ± 0.01 pN/mn, P<0.0001) in septic mice (1 mg E. coli lipopolysaccharides (LPS)/kg BW i.p.) compared to controls. Corresponding in vitro experiments revealed that sepsis-associated mediators, such as thrombin, LPS or Tumor Necrosis Factor-α alone were sufficient to rapidly decrease eGC thickness (-50%, all P<0.0001) and stiffness (-20% P<0.0001) on HPMEC. In summary, AFM nanoindentation is a promising novel approach to uncover mechanisms involved in deterioration and refurbishment of the eGC in sepsis.
Journal Article
Commentary: The Clinical Impact of the C0/D Ratio and the CYP3A5 Genotype on Outcome in Tacrolimus Treated Kidney Transplant Recipients
The authors report that our group has shown that fast Tac metabolism (C0/D ratio <1.05 ng/ml/mg) is associated with a faster decline in renal function, a higher incidence of calcineurin inhibitor nephrotoxicity (CNIT) and BK nephropathy and a lower survival rate (Tholking et al., 2014;Tholking et al., 2016;Schutte-Nutgen et al., 2019;Tholking et al., 2019). Conclusion Despite limited data on long-term outcome in recipients of solid organ transplants after conversion from IR- or ER-Tac to other immunosuppressants, we have already shown it can be safe and useful in transplant patients with Tac-related adverse effects. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Journal Article
Nodular Lymphoid Hyperplasia as Incidental Finding of Suspect Pulmonary Mass
Nodular lymphoid hyperplasia of the lung is a rare disease of polyclonal lymphoid proliferation. The incidental finding of a solid nodular lesion with irregular margins adjacent to the visceral pleura in the reported case was highly suggestive of malignancy. The present report underscores the typical immunohistochemical findings and the benign course of nodular lymphoid hyperplasia. The current knowledge about disease aetiology and the value of different diagnostic tools to distinguish nodular lymphoid hyperplasia from other pulmonary lymphoid lesions are summarized by a review of the literature. Surgical resection is not only diagnostic but also curative with no evidence so far that NLH can regress without operation. The present case shows the spontaneous regression of NLH after CT-guided biopsy indicating that an alternative, less invasive diagnostic approach has curative potential.
Journal Article
Case report: membranoproliferative glomerulonephritis associated with Q fever causing chronic endocarditis
Background
Membranoproliferative glomerulonephritis is a rare entity which can be a result from autoimmune diseases, caused by various medications and infections.
Case presentation
We herein present the case of a 62-year-old male patient who presented with fatigue and was found to have severe anemia, impaired renal function, and nephrotic syndrome. A renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) of the immune complex type with activation of the classical complement pathway. Further investigations led to the diagnosis of a chronic
Coxiella burnetii
-infection (Q fever), likely acquired during cycling trips in a region known for intensive sheep farming. Additionally, the patient was found to have a post endocarditic destructive bicuspid aortic valve caused by this pathogen. Treatment with hydroxychloroquine and doxycycline was administered for a duration of 24 months. The aortic valve was replaced successfully and the patient recovered completely.
Conclusions
Early detection and targeted treatment of this life-threatening disease is crucial for complete recovery of the patient.
Journal Article
A Comprehensive Review of Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome
Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disorder, characterized by acute tubulointerstitial nephritis and uveitis. It poses diagnostic challenges due to the mostly asynchronous onset of renal and ocular manifestations, as well as the variety of differential diagnoses. This review provides an overview of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management strategies. Methods: A comprehensive review of the peer-reviewed literature, including studies and case reports, was conducted. Results: The etiology of TINU syndrome involves an autoimmune reaction to renal and ocular antigens, leading to interstitial inflammation and tubular damage in the kidneys, and anterior uveitis with acute onset of flares. Diagnostic criteria based on ocular examination, laboratory parameters, and renal biopsy emphasize the need to exclude other systemic diseases. TINU syndrome accounts for approximately 2% of all uveitis cases. Primary treatment consists of corticosteroids, while immunomodulatory therapies (methotrexate, azathioprine, mycophenolate mofetil, or biologic agents) are reserved for refractory cases. Recurrence of uveitis appears to be more common than that of nephritis. Conclusions: TINU syndrome is rare and requires clinical suspicion for accurate diagnosis. Early diagnosis and initiation of treatment are crucial for achieving favorable outcomes. Advances in the understanding of its pathogenesis and treatment have improved patient outcomes. Further research is needed to investigate the underlying triggers and mechanisms in order to develop targeted therapies.
Journal Article
The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation
The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient's risk management strategies.
Journal Article
The Role of Renewable Gas Energy Communities in Austria’s Energy Transformation
Renewable energy communities (RECs) can play a vital role in integrating renewable gases like biomethane into Austria’s energy system. This study examines critical gaps in national regulations for renewable gas RECs (short ‘gas RECs’) and the need for clarification in certification processes. The novelty of this study lies in the development of energy community (EC) variants for renewable gas, focusing on Industrial, Communal, and Agricultural Symbiosis. A case study of Bruck/Leitha evaluates the techno-economic feasibility of gas RECs, showing that while biomethane’s production costs are higher than natural gas by 2.14 cents/kWh in 2021, it offers greater price stability. Although biomethane is economically less competitive, it provides significant ecological benefits. The results underline the importance of policy advancements, including funding mechanisms and regulatory clarity, to support the integration of gas RECs into Austria’s energy system.
Journal Article
Belatacept as a Treatment Option in Patients with Severe BK Polyomavirus Infection and High Immunological Risk—Walking a Tightrope between Viral Control and Prevention of Rejection
Balancing the immune system with immunosuppressive treatment is essential in kidney transplant recipients to avoid allograft rejection on the one hand and infectious complications on the other. BK polyomavirus nephropathy (BKPyVAN) is a viral complication that seriously threatens kidney allograft survival. Therefore, the main treatment strategy is to reduce immunosuppression, but this is associated with an increased rejection risk. Belatacept is an immunosuppressant that acts by blocking the CD80/86-CD28 co-stimulatory pathway of effector T-cells with marked effects on the humoral response. However, when compared with calcineurin-inhibitors (CNI), the cellular rejection rate is higher. With this in mind, we hypothesized that belatacept could be used as rescue therapy in severely BKPyV-affected patients with high immunological risk. We present three cases of patients with BKPyVAN-associated complications and donor-specific antibodies (DSA) and one patient who developed T-cell-mediated rejection after a reduction in immunosuppression in response to BKPyVAN. Patients were switched to a belatacept-based immunosuppressive regimen and showed significantly improved viral control and stabilized graft function. The cases presented here suggest that belatacept is a potential treatment option in the complicated situation of refractory BKPyV infection in patients with high immunological risk.
Journal Article