Ludwig Wagner

Medical University of Vienna | MedUni Vienna · Department of Medicine III

Background Chronic kidney disease patients show a high mortality in cases of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV‑2) infection. Thus, information on the sero-status of nephrology personnel might be crucial for patient protection; however, limited information exists about the presence of SARS-CoV‑2 antibodies in asymptomatic i...

Overproduction of human light chains (LCs) and immunoglobulins can result in various forms of renal disease such as cast nephropathy, monoclonal immunoglobulin deposition disease, LC proximal tubulopathy, AL amyloidosis, and crystal storing histiocytosis. This is caused by cellular uptake of LCs and overwhelmed intracellular transport and degradati...

Background Immune-modulatory treatments have so far shown limited clinical activity in primary brain tumours. We aimed to investigate soluble programmed death receptor ligand 1 (sPD-L1) as systemic inflammation parameter in patients with brain tumour. Methods EDTA plasma was collected from 81 glioma (55 glioblastoma (GBM), 26 lower-grade glioma (L...

Background Sepsis-related acute kidney injury (AKI) is associated with high morbidity and mortality among patients. Underlying pathomechanisms include capillary leakage and fluid loss into the interstitial tissue and constant exposure to pathogens results in activation of inflammatory cascades, organ dysfunction and subsequently organ damage. Meth...

Background: Chronic kidney disease patients show a high mortality in case of a SARS-CoV-2 infection. Thus, to be informed on Nephrology personnel's sero-status might be crucial for patient protection. However, limited information exists about the presence of SARS-CoV-2 antibodies in asymptomatic individuals. Methods: We examined the seroprevalence...

Background and Aims The urinary microbiome harbors a great repertoire of bacteria, which possess an immense potential for the biosynthesis of different biochemical products such as polyketide synthases. Traditionally such compounds have been utilized as pharmaceutical drugs, for example as antibiotics or cytostatic substances or agrochemical agents...

Patients after solid organ kidney transplantation (KTX) often suffer from acute kidney injury (AKI). Parameters as serum creatinine indicate a loss of kidney function, although no distinction of the cause and prognosis can be made. Imaging tools measuring kidney function have not been widely in clinical use. In this observational study we evaluated...

Introduction Secretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients.1,2,3 Up to this day, no study on SCGN levels in patients with gestational diabetes mellitus (GDM) has bee...

An amendment to this paper has been published and can be accessed via the original article.

Background: In the past urine was considered sterile. Through the introduction of next generation sequencing, it has become clear that a urinary microbiome exists. Acute kidney injury (AKI) represents a major threat to kidney transplant recipients. Remarkable changes in the urinary metabolome occur during AKI, which may influence the urinary micro...

Background Complement factor C3 represents the central component of the complement cascade and its activation split product C3a plays an important role in inflammation and disease. Many human disorders are linked to dysregulation of the complement system and alteration in interaction molecules. Therefore, various therapeutic approaches to act on th...

Psychostimulant use is an ever-increasing socioeconomic burden, including a dramatic rise during pregnancy. Nevertheless, brain-wide effects of psychostimulant exposure are incompletely understood. Here, we performed Fos-CreER T2 –based activity mapping, correlated for pregnant mouse dams and their fetuses with amphetamine, nicotine, and caffeine a...

Background Monoclonal overproduction of kappa and/or lambda light chains might result in renal light chain deposition disease. Light chain associated cast nephropathy and renal AL-amyloidosis represent two further pathologies going along with monoclonal gammopathy of renal significance and multiple myeloma. While cast nephropathy often manifests wi...

Background Immune therapies targeting the programmed cell death receptor (ligand) 1 (PD-1/PD-L1) axis have shown remarkable activity in a variety of solid tumors. While substantial responses were observed in asymptomatic patients with brain metastases (BM), their clinical activity in primary brain tumors remains limited. In a cohort of adult brain...

The plasma soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker for focal segmental glomerulosclerosis (FSGS), but its value is under discussion because of ambiguous results arising from different ELISA methods in previous studies. The aim of this study was to compare diagnostic performance of two leading suPAR ELISA kits an...

Psychostimulant use is an ever-increasing socioeconomic burden, including a dramatic rise during pregnancy. Nevertheless, brain-wide effects of psychostimulant exposure are incompletely understood. Here, we performed Fos-CreER T2 -based activity mapping, correlated for pregnant mouse dams and their fetuses with amphetamine, nicotine and caffeine ap...

BACKGROUND Immune modulating therapies are a promising treatment approach in patients with primary brain tumors, however their clinical efficacy is still under investigation as the systemic inflammatory responses are potentially challenged by the brain’s tight immune regulatory mechanisms. Here, we aimed to investigate soluble PD-L1 (sPD-L1) in the...

Background: Acute kidney injury represents a major threat to the transplanted kidney. Nevertheless, these kidneys have the potential to fully recover. Tubular regeneration following acute kidney injury is driven by the regenerative potential of tubular cells originating from a tubular stem cell pool. We investigated urinary sediments of acute kidn...

Calcium-binding proteins are widely used to distinguish neuronal subsets in the brain. This study focuses on secretagogin, an EF-hand calcium sensor, to identify distinct neuronal populations in the brainstem of several vertebrate species. By using neural tube whole mounts of mouse embryos, we show that secretagogin is already expressed during the...

Calcium is one of the most important signaling factors in mammalian cells. Specific temporal and spatial calcium signals underlie fundamental processes such as cell growth, development, circadian rhythms, neurotransmission, hormonal actions and apoptosis. In order to translate calcium signals into cellular processes a vast number of proteins bind t...

Background Novel drugs for Clostridium difficile (C. difficile) infections have been proven to reduce recurrent infections. Because of their high financial costs, identification of patients at high risk for recurrence is essential to provide optimal treatment. The ATLAS score’s ability to predict 90-day recurrence, disease complications and 1‑year...

Abstract Strongyloides stercoralis is not hyperendemic in European countries but has been increasing in prevalence due to migration and travel. The infection is characterized by a mostly asymptomatic course or nonspecific symptoms in healthy subjects. However, immunosuppression or chemotherapy have been described as leading triggers for Strongyloid...

Background: Acute kidney injury represents a major threat to the transplanted kidney. Nevertheless, these kidneys have the potential to fully recover. Tubular regeneration following acute kidney injury is driven by the regenerative potential of tubular cells originating from a tubular stem cell pool. We investigated urinary sediments of acute kidne...

Background Acute kidney injury (AKI) is frequently observed in serious infections, following nephrotoxic medication, surgery and trauma. Here we tested whether the detection of two recently identified biomarkers for AKI, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding Protein 7 (IGFBP7), depends on the expres...

Fold gene expression. Itemized details of pseudonymised patients including TIMP-2 and IGFBP7 fold gene expression. (XLSX)

Ca(2+)-sensor proteins are generally implicated in insulin release through SNARE interactions. Here, secretagogin, whose expression in human pancreatic islets correlates with their insulin content and the incidence of type 2 diabetes, is shown to orchestrate an unexpectedly distinct mechanism. Single-cell RNA-seq reveals retained expression of the...

Background Critically ill patients in intensive care face hazardous conditions. Among these, acute kidney injury (AKI) is frequently seen as a result of sepsis. Early diagnosis of kidney injury is of the utmost importance in the guidance of interventions or avoidance of treatment-induced kidney injury. On these grounds, we searched for markers that...

The rostral migratory stream (RMS) is viewed as a glia-enriched conduit of forward-migrating neuroblasts in which chemorepulsive signals control the pace of forward migration. Here we demonstrate the existence of a scaffold of neurons that receive synaptic inputs within the rat, mouse, and human fetal RMS equivalents. These neurons express secretag...

Background: Acute kidney injury (AKI) is a life threatening condition. Despite intensive care treatment the occurrence cannot be predicted as very little indicators exist for direct measurement when tubular epithelial cell injury takes place. We therefore searched for novel peptide indicators expressed at intracellular level at the proximal kidney...

Structural and biochemical alterations of the microtubule-associated protein tau (MAPT) are associated with degenerative disorders referred to as tauopathies. We have previously shown that MAPT is present in human islets of Langerhans, human insulinomas, and pancreatic beta-cell line models, with biophysical similarities to the pathological MAPT in...

Background: Acute kidney injury is frequently observed at the intensive care unit, after surgery, and after toxic drug administration. A rise in serum creatinine and a fall in urine output are consequences of much earlier injury to the most sensitive part of tubular cells located at the proximal tubule. The aim of the present study was to investig...

Brain metastases (BM) are the most common brain tumors of adults and are associated with fatal prognosis. Formation of new blood vessels, named angiogenesis, was proposed to be the main hallmark of the growth of BM. Previous preclinical evidence revealed that angiogenic blockage might be considered for treatment; however, there were varying respons...

The Hedgehog pathway is an important regulator of early tissue patterning and stem cell propagation. It was found to be aberrantly activated in numerous types of human cancer and might be relevant in cancer stem cells. The identification of adult stem cells in the pituitary raised the question if tumor-initiating cells and Hedgehog signaling are in...

A hierarchical hormonal cascade along the hypothalamic-pituitary-adrenal axis orchestrates bodily responses to stress. Although corticotropin-releasing hormone (CRH), produced by parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) and released into the portal circulation at the median eminence, is known to prime downstream hormo...

The diabetes prevention paradigm envisages the application of strategies that support the maintenance of appropriate β-cell numbers. Herein we show that overexpression of CXC chemokine ligand12 (CXCL12) considerably improves the viability of isolated rat Langerhans islet cells and Rin-5F pancreatic β-cells after hydrogen peroxide treatment. In rat...

2040 Background: Myxopapillary ependymoma (MPE) is a very rare tumor of the distal spinal cord. Despite benign histopathology, local recurrences occur in approximately 30% of patients and distant metastases have been described in few cases. We investigated candidate tissue and blood biomarkers in a rare MPE series. Methods: Formalin fixed paraffin...

Myxopapillary ependymoma (MPE) is a rare tumor of the distal spinal cord. Despite benign histopathology, local recurrences occur in ~30 % of patients and distant metastases have been described in few cases. MPE tumor cells typically express glial fibrillary acidic protein (GFAP), which could be released to the circulation. In this current report, w...

CNS tumors comprise approximately 120 histological subtypes. Advances of surgical resection, radiation and systemic therapy have increased the survival rates of distinct types of CNS tumor patients. There is growing interest in identification of diagnostic, prognostic or predictive blood biomarkers in CNS tumor patients, and emerging studies indica...

The transcription factor and proto-oncogene GLI1 is the terminal mediator of the Hedgehog signalling pathway which is involved in developmental processes, stem cell maintenance and cell proliferation. Although the pathway is mainly active during embryogenesis and tissue repair, it is frequently reactivated in several cancer types. Based on these fi...

Glioblastoma is the most frequent primary brain tumour in adults. Recent therapeutic advances increased patient's survival, but tumour recurrence inevitably occurs. The pathobiological mechanisms involved in glioblastoma recurrence are still unclear. MicroRNAs are small RNAs proposed o have important roles for cancer including proliferation, aggres...

Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and...

Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to...

Background Secretagogin (Scgn), a member of the EF-hand calcium-binding protein (CaBP) superfamily, has recently been found in subsets of developing and adult neurons. Here, we have analyzed the expression of Scgn in dorsal root ganglia (DRGs) and trigeminal ganglia (TGs), and in spinal cord of mouse at the mRNA and protein levels, and in compariso...

Figure S1. (A) Overview of in situ hybridization to detect Scgn mRNA in the adult mouse olfactory bulb using a riboprobe. Open rectangles indicate the locations of (A1,A2). (A1) Cellular Scgn mRNA detection (arrowheads) in the external plexiform layer (ML: mitral cells are negative). (A2) Hybridization signal, although at markedly lower levels, is...

Background: There is little knowledge on blood alterations of glioblastoma. We had the opportunity to investigate markers from plasma taken 66, 36, and 6 months before glioblastoma in a patient in the VITA study. Methods: We determined S100B, secretagogin, neuropeptide-Y, micro-RNA-21, let-7, micro-RNA-128, and micro-RNA-342-3p in our patient an...

Background: MicroRNAs are proposed as plasma biomarkers in cancer. Glioblastoma is the most frequent primary brain tumor of adults. MicroRNA-21 was shown to induce glioblastoma growth. Aims: To evaluate the circulating microRNA-21 in glioblastoma patients. Methods: MicroRNA-21 copies in glioblastoma plasma (n = 10, before surgery and during/af...

Secretagogin is a calcium binding protein (CBP) highly expressed in neuroendocrine cells. It has been shown to be involved in insulin secretion from pancreatic beta cells and is a strong candidate as a biomarker for endocrine tumors, stroke, and eventually psychiatric conditions. Secretagogin has been hypothesized to exert a neuroprotective role in...

Three-dimensional reconstruction of a hippocampal interneuron co-expressing Parvalbumin and Secretagogin. Rat brain slices were immunostained for Secretagogin (green) and Parvalbumin (red). Z-stacks were taken on a Leica confocal microscope from a Parvalbumin-positive interneuron in the CA1 region of the hippocampus co-expressing Secretagogin. The...

Although type 2 diabetes mellitus (DM) is a chronic metabolic disorder with multiple etiologies, obesity has been constantly linked with insulin resistance and manifestation of type 2 DM. In addition, obesity is associated with hypertension, dyslipidemia, and fatty liver disease and is regarded as a subclinical inflammatory condition characterized...

Several blood biomarkers have been established for the early diagnosis, screening and follow-up of non central nervous system cancers. However, there is lack of knowledge on biochemical blood alterations in brain tumor patients. In this study, we prospectively collected blood plasma samples of 105 adult brain tumor patients with diffuse low-grade g...

2024 Background: Glioblastoma is the most common and aggressive primary brain tumour in adults. There is lack of knowledge on biochemical blood alterations prior to clinical diagnosis of glioblastoma. We had the rare opportunity to investigate selected blood markers from plasma samples taken 12, 42 and 72 months before tumor manifestation in a glio...

There is evidence that diabetic polyneuropathy (PNP) is associated with reduced bone mineral density (BMD) in type 1 diabetes but little is known about the impact of diabetic PNP on bone metabolism in type 2 diabetes. The aim of this study was to evaluate differences in bone metabolism by measuring markers of bone turnover and BMD in men and postme...

Evaluation of: Powers MP, Alvarez K, Kim HJ, Monzon FA. Molecular classification of adult renal epithelial neoplasms using microRNA expression and virtual karyotyping. Diagn. Mol. Pathol. 20(2), 63-70 (2011). Novel reliable techniques for the exact classification of renal epithelial neoplasms, especially in cases with morphological ambiguity, are o...

Secretagogin is a calcium-binding protein whose expression is characterised in neuroendocrine, pancreatic, and retinal cells. We have used an array-based proteomic approach with the prokaryotically expressed human protein array (hEx1) and the eukaryotically expressed human protein array (Protoarray) to identify novel calcium-regulated interaction n...

Type 2 diabetes mellitus is characterized by increasing plasma levels of vascular endothelial growth factor (VEGF) and selectively Angiopoitin-2 (Ang-2). As VEGF correlated with diabetic microangiopathy including diabetic polyneuropathy (DPN), we aimed in this study to determine the relationship between Ang-2 and DPN in type 2 diabetic patients. In...

Type 2 diabetes mellitus is characterized by increasing plasma levels of vascular endothelial growth factor (VEGF) and selectively Angiopoitin-2 (Ang-2). As VEGF correlated with diabetic microangiopathy including diabetic polyneuropathy (DPN), we aimed in this study to determine the relationship between Ang-2 and DPN in type 2 diabetic patients. In...

Type 2 diabetes is associated with increased levels of Angiopoietin-2 (Ang-2) and soluble Tie-2 (sTie-2), but its impact on vascular disease is still unknown. This study aimed to further explore the associations of Ang-2 and sTie-2 with metabolic control and diabetic complications. In a cross-sectional designed study, levels of Ang-2 and sTie-2 as...

Serum- and glucocorticoid-regulated kinase-1 (SGK1) is a glucocorticoid early-response gene; its function, however, has been elucidated mainly in the context of mineralocorticoid signaling. Here, we investigate the expression and function of SGK1 in the pituitary gland, one of the primary glucocorticoid targets. SGK1 is expressed in the human pitui...

Renal cell carcinomas are divided into several subgroups according to their histopathologic characteristics. The outcome, therapy responses, and the applicability of molecular-targeted therapies depend on the tumor classification and on the tumor stage. Recent advances within the biomarker research facilitated the exact classification of the molecu...

Frequent concomitant manifestation of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has been recently demonstrated by epidemiological studies. This might be due to functional similarities between β-cells and neurons, such as secretion on demand of highly specific molecules in a tightly controlled fashion. An additional similarity rep...

Neuropathological features in Alzheimer's Disease (AD) include the presence of hyperphosphorylated forms of the microtubule-associated tau protein (tau) in hippocampal neurones. Numerous studies indicate a neuroprotective effect of calcium-binding proteins (Ca2+ binding proteins) in neurodegenerative diseases (e.g., AD). Secretagogin is a newly des...

Secretagogin is a hexa EF-hand Ca(2+)-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. The protein has been noted for its expression in specific neuronal subtypes in the support of hierarchical organizing principles in the mammalian brain. Secretagogin has previously been found to interact with SNAP25 involved in...

Neuropeptide Y (NPY) is an important hormone in appetite regulation. Although the contribution of NPY to metabolic disease has been previously demonstrated, there are only a few reports addressing NPY plasma levels under distinct diabetic conditions. In this study we evaluated NPY plasma levels in diabetes mellitus type 2 (DM2) patients with (n=34)...

Characterization of gene products originating from undefined open reading frames and delineation of biological functions has become the task after the human genome has been decoded. We cloned the human C20orf 116 and defined its transcript in liver, kidney and various brain regions by Northern analysis. Antibodies against recombinant protein used f...

Tauopathies have been associated with Alzheimer's disease (AD), which frequently manifests together with diabetes mellitus type 2. Calcium-binding proteins such as the recently identified secretagogin (SCGN) might exert protective effects. As pancreatic beta-cells and neurons share common electrophysiological properties, we investigated the appeara...

We detected distinct plasma concentration profiles of S100B, neuropeptide Y, and secretagogin in 3 of 191 patients enrolled in a previous study investigating brain-tissue-related markers in the blood of patients with atrial fibrillation. Intriguingly, 2 of these 3 patients, both of whom were without neurological symptoms at the time of blood sampli...

Angiopoiesis and angiopoietic growth factors are of considerable importance in the development and progression of intracranial tumours. However, knowledge of the plasma detectability of distinct angiogenic factors in patients with brain tumour is very limited. This study evaluates the plasma concentrations of the angiogenic factors angiopoietin-2 (...

Expression of heat shock proteins has been described in different tissues relevant to human reproduction, including placenta. AlphaB-crystallin is a member of the small heat shock protein family (sHsp) exerting biologically important chaperon functions. Immunofluorescence; immunoblot analysis; quantitative real-time-PCR; CpG island methylation anal...

Identification of plasma markers indicative for atrial fibrillation-associated silent brain lesions. 1. Comparative determination of the plasma concentrations of secretagogin, S100B, neuropeptide Y, brain fatty acid binding protein, matrix metalloprotease 9, brain natriuretic peptide, and of D-Dimer in 222 patients with atrial fibrillation and 28 c...

This study was performed on the basis of previously obtained investigative gene array data concerning the over-expression of CXCL12/SDF-1 in human insulinomas versus human pancreatic islet preparations. The presence of CXCL12/SDF-1 was studied by RT-qPCR in human insulinomas (n=8) versus pancreatic islets (n=3), and was found to be significantly up...

In the present study, we characterized the gene product of open reading frame 3 encoded at human chromosome 20 (C20orf3), which represents a member of the lactonohydrolase super family. Multiple-tissue Northern blot analysis showed ubiquitous expression of the 2.4 kb transcript coding for 416 amino acids, with highest levels in human liver, placent...

The pathological findings in Alzheimer's disease (AD) are partly attributed to alterations in calcium-binding protein (CBP) functions. We showed previously that immunoreactivity of secretagogin, a recently cloned CBP, in the human hippocampus is restricted to pyramidal neurones and that the amount of immunoreactive neurones does not differ between...

Aiming to identify signalling pathways relevant for ss-cell growth we performed an explorative micro-array analysis comparing the gene expression profiles of three human insulinomas and one normal pancreatic islet preparation. This revealed an insulinoma-associated down-regulation of the transforming growth factor beta 1 (TGF-beta1) and its target...