A5009309257- Dialysis and Renal Disease Management
- Parathyroid Disorders and Treatments
- Chronic Kidney Disease and Diabetes
- Renal and Vascular Pathologies
- Muscle and Compartmental Disorders
- Peripheral Artery Disease Management
- Bone health and treatments
- Pancreatitis Pathology and Treatment
- Renal Transplantation Outcomes and Treatments
- Biochemical effects in animals
- Bone health and osteoporosis research
- Aortic aneurysm repair treatments
- Organ Transplantation Techniques and Outcomes
- Lymphatic Disorders and Treatments
- Erythropoietin and Anemia Treatment
- Lymphatic System and Diseases
- Renal and related cancers
- Tissue Engineering and Regenerative Medicine
- Acute Kidney Injury Research
- Barrier Structure and Function Studies
- Iron Metabolism and Disorders
- Digestive system and related health
- Dermatological and Skeletal Disorders
- Advanced Glycation End Products research
- Diet, Metabolism, and Disease
University Hospital Heidelberg
2014-2024
Heidelberg University
2015-2024
Heidelberg University
2020-2024
German Center for Pediatric and Adolescent Rheumatology
2017-2023
Johannes Kepler University of Linz
2021
Abstract The peritoneum plays an essential role in preventing abdominal frictions and adhesions can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal 69 omental specimens were obtained from 107 patients (0.1–60 years) undergoing surgery for disease affecting the automated quantitative histomorphometry immunohistochemistry. mesothelial cell layer morphology protein expression pattern is similar...
Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis, and ultrafiltration failure. Influencing PM integrity pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated uptake has not been studied. In this study, wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, or without addition of selective SGLT2 inhibitor dapagliflozin. structural changes, capacity, equilibration testing...
Cardiovascular disease (CVD) is the leading cause of increased mortality in patients with CKD and further aggravated by peritoneal dialysis (PD). Children are devoid preexisting CVD provide unique insight into specific uremia- PD-induced pathomechanisms CVD. We obtained specimens from children stage 5 at time PD catheter insertion (CKD5 group), established (PD age-matched nonuremic controls (n=6/group). microdissected omental arterioles tissue layers not directly exposed to fluid used...
Clinical studies suggested that endothelial dysfunction and damage could be involved in the development severity of acute graft-versus-host disease (aGVHD). Accordingly, we found increased percentage apoptotic Casp3+ blood vessels duodenal colonic mucosa biopsies patients with severe aGVHD. In murine experimental aGVHD, detected microstructural reduced pericyte coverage accompanied by expression tight junction proteins leading to leakage aGVHD target organs. During intestinal vasculature...
The impact of peritoneal dialysis (PD) associated peritonitis on membrane integrity is incompletely understood. Children are particularly suited to address this question, since they largely devoid preexisting tissue damage and life-style related alterations. Within the International Peritoneal Biobank, 85 standardized parietal samples were obtained from 82 children neutral pH PD fluids with low glucose degradation product (GDP) content. 37 patients had a history 16 two or more episodes. Time...
Understanding and targeting the molecular basis of peritoneal solute protein transport is essential to improve dialysis (PD) efficacy patient outcome. Supplementation PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small reduced loss in a recent clinical trial. Transepithelial resistance 10 kDa 70 dextran were measured primary human endothelial cells (HUVEC) exposed conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) low GDP (LPDF) without AlaGln. Zonula...
Lithium added to peritoneal dialysis fluid protects mesothelial cells and attenuates fibrosis angiogenesis by reducing αB-crystallin.
[Figure: see text].
Peritoneal dialysis (PD) is a valuable 'home treatment' option, even more so during the ongoing Coronavirus pandemic. However, long-term use of PD limited by unfavourable tissue remodelling in peritoneal membrane, which associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while involvement other angiogenic signaling pathways still poorly understood. Here, we have identified crucial contribution mesothelial...
Long-term clinical outcome of peritoneal dialysis (PD) depends on adequate removal small solutes and water. The endothelium represents the key barrier transport dysfunction is associated with vascular changes. Alanyl-glutamine (AlaGln) has been shown to counteract PD-induced deteriorations but effect changes not yet elucidated. Using multiplexed proteomic bioinformatic analyses we investigated molecular mechanisms pathology in-vitro (primary human umbilical vein endothelial cells, HUVEC)...
Abstract Aim Although of potential biomedical relevance, dipeptide metabolism has hardly been studied. We found the dipeptidase carnosinase‐2 (CN2) to be abundant in human proximal tubules, which regulate water and solute homeostasis. therefore hypothesized, that CN2 a key metabolic role, impacting tubular transport function. Methods A knockout gene ( CNDP2 ‐KO) was generated tubule cells characterized by metabolomics, RNA‐seq analysis, paracellular permeability analysis ion transport....
Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney (CKD). We hypothesized that CKD associated systemic damage to the microcirculation, preceding macrovascular pathology. To assess degree "uremic microangiopathy", we have measured microvascular density biopsies omentum children CKD.Omental tissue was collected from 32 healthy (0-18 years) undergoing elective abdominal surgery 23 age-matched cases stage 5...
Ultrafiltration decline is a progressive issue for patients on chronic peritoneal dialysis (PD) and can be caused by angiogenesis induced PD fluids. A recent pediatric trial suggests better preservation of ultrafiltration with bicarbonate versus lactate buffered fluid; underlying molecular mechanisms are unknown.Angiogenic cytokine profile, tube formation capacity Receptor Tyrosine Kinase translocation were assessed in primary human umbilical vein endothelial cells following incubation...
Abstract Chronic kidney disease (CKD) greatly increases the risk for cardiovascular (CVD). However, molecular mechanisms underlying CKD-induced arterial remodeling are largely unknown. We performed a systematic analysis of biopsies from children with stage 5 predialysis CKD participating in Cardiovascular Comorbidity Children Kidney Disease (4 C) study. For comparison, we studied without CKD, coronary bypass vessels adults atherosclerotic heart and aortic sections subtotally nephrectomized...
Endothelial and epithelial barrier function is crucial for the maintenance of physiological processes. The paracellular permeability depends on composition spatial distribution cell-to-cell tight junctions (TJ). Here, we provide an experimental workflow that yields several layers data in setting a single endothelial cell monolayer. Human umbilical vein cells were grown Transwell filters. Transendothelial electrical resistance (TER) 10 kDa FITC dextran flux measured using Alanyl-Glutamine...
ABSTRACT Background The unphysiological composition of peritoneal dialysis (PD) fluids induces progressive fibrosis, hypervascularization and vasculopathy. Information on these alterations after kidney transplantation (KTx) is scant. Methods Parietal tissues were obtained from 81 pediatric patients with chronic disease stage 5 (CKD5), 72 children PD low glucose degradation product (GDP) fluids, 20 4–8 weeks KTx preceding low-GDP PD. Tissues analyzed by digital histomorphometry quantitative...
Carnosine and anserine supplementation markedLy reduce diabetic nephropathy in rodents. The mode of nephroprotective action both dipeptides diabetes, via local protection or improved systemic glucose homeostasis, is uncertain. Global carnosinase-1 knockout mice (Cndp1-KO) wild-type littermates (WT) on a normal diet (ND) high fat (HFD) (n = 10/group), with streptozocin (STZ)-induced type-1 diabetes 21-23/group), were studied for 32 weeks. Independent diet, Cndp1-KO had 2- to 10-fold higher...
Chronic Kidney Disease (CKD) is associated with markedly increased cardiovascular (CV) morbidity and mortality. inflammation, a hallmark of both CKD CV diseases (CVD), believed to drive this association. Pro-inflammatory endogenous TLR agonists, Damage-Associated Molecular Patterns (DAMPs), have been found elevated in patients’ plasma suggested promote CVD, however, confirmation their involvement, the underlying mechanism(s), extent which individual DAMPs contribute vascular pathology...
Next to the skin, peritoneum is largest human organ, essentially involved in abdominal health and disease states, but information on peritoneal paracellular tight junctions transcellular channels transporters relative transmembrane transport scant. We studied their localization quantity by immunohistochemistry confocal microscopy health, chronic kidney (CKD) dialysis (PD), with latter allowing for functional characterizations, a total of 93 individuals (0-75 years). Claudin-1 -5, -15, zonula...
Introduction Peritoneal dialysis fluids (PDF) differ with respect to osmotic and buffer compound, pH glucose degradation products (GDP) content. The impact on peritoneal membrane integrity is still insufficiently described. We assessed global genomic effects of PDF in primary human mesothelial cells (PMC) by whole genome analyses, quantitative real-time polymerase chain reaction (RT-PCR) functional measurements. Methods PMC isolated from omentum non-uremic patients were incubated...