Secondary Immunodeficiency Related to Kidney Disease (SIDKD) - Definition, Unmet Need and Mechanisms

2021 ◽  
pp. ASN.2021091257
Author(s):  
Stefanie Steiger ◽  
Jan Rossaint ◽  
Alexander Zarbock ◽  
Hans-Joachim Anders
Keyword(s):  
Kidney Disease ◽  
Immune Responses ◽  
Host Defense ◽  
Unmet Need ◽  
Secondary Immunodeficiency ◽  
Research Activities ◽  
Medical Need ◽  
Rigorous Research ◽  
Serious Infections ◽  
Definition Of

Kidney disease is a known risk factor for poor outcome of COVID-19 and many other serious infections. Vice versa, infection ranks second as cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiological, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an immanent unmet medical need that requires rigorous research activities at all levels, too, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known so far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia as well as shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.

scholarly journals Adding life to their years: the current state of pediatric palliative care in CKD

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0000282021
Author(s):  
Taylor R House ◽  
Aaron Wightman
Keyword(s):  
Quality Of Life ◽  
Palliative Care ◽  
Kidney Disease ◽  
Pediatric Nephrology ◽  
Unmet Need ◽  
Routine Care ◽  
Pediatric Palliative Care ◽  
Disease States ◽  
Definition Of

Despite continued advances in medical treatment, pediatric chronic kidney disease (CKD) remains an unremitting, burdensome condition characterized by decreased quality of life and earlier death.(1-7) These burdens underscore the need for integration of pediatric palliative care (PPC) into nephrology practice. Pediatric palliative care is an evolving field which strives to 1) relieve physical, psychological, social, practical and existential suffering; 2) improve quality of life; 3) facilitate decision-making; and 4) assist with care coordination in children with life-threatening or life-shortening conditions.(8) Integration of palliative care into routine care has already begun for adults with kidney disease and children with other chronic diseases, yet, similar integration has not occurred in pediatric nephrology.(9,10) This review serves to provide a comprehensive definition of PPC, highlight the unmet need in pediatric nephrology and current integration efforts, discuss the state of palliative care in adult nephrology and analogous chronic pediatric disease states, and finally to introduce future opportunities for study.

scholarly journals Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease

2007 ◽  
Vol 82 (6) ◽  
pp. 3021-3030 ◽  
Author(s):  
Kevin B. Walsh ◽  
Melissa B. Lodoen ◽  
Robert A. Edwards ◽  
Lewis L. Lanier ◽  
Thomas E. Lane
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Host Defense ◽  
Nk Cell ◽  
Hepatitis Virus ◽  
Innate Immune ◽  
Liver Pathology ◽  
Innate Immune Responses ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.

scholarly journals New Potential Biomarkers for Chronic Kidney Disease Management—A Review of the Literature

2020 ◽  
Vol 22 (1) ◽  
pp. 43
Author(s):  
Irina Lousa ◽  
Flávio Reis ◽  
Idalina Beirão ◽  
Rui Alves ◽  
Luís Belo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Renal Damage ◽  
Recent Literature ◽  
Therapeutic Interventions ◽  
Review Of The Literature ◽  
Medical Need ◽  
Early Use ◽  
Reasonable Approach

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. The biomarkers currently used in clinical practice are considered relevant when there is already significant renal impairment compromising the early use of potentially successful therapeutic interventions. More sensitive and specific biomarkers to detect CKD earlier on and improve patients’ prognoses are an important unmet medical need. The aim of this review is to summarize the recent literature on new promising early CKD biomarkers of renal function, tubular lesions, endothelial dysfunction and inflammation, and on the auspicious findings from metabolomic studies in this field. Most of the studied biomarkers require further validation in large studies and in a broad range of populations in order to be implemented into routine CKD management. A panel of biomarkers, including earlier biomarkers of renal damage, seems to be a reasonable approach to be applied in clinical practice to allow earlier diagnosis and better disease characterization based on the underlying etiologic process.

Digital competences of the workforce – a research topic?

2017 ◽  
Vol 23 (3) ◽  
pp. 721-734 ◽  
Author(s):  
Matthias Murawski ◽  
Markus Bick
Keyword(s):  
Research Topic ◽  
Future Research ◽  
Digital Competence ◽  
Content Type ◽  
Research Activities ◽  
Starting Point ◽  
Pros And Cons ◽  
Definition Of ◽  
The Individual ◽  
Practical Implications

Purpose Considering working in the digital age, questions on the consequences for the individual workers are, so far, often neglected. The purpose of this paper is to deal with the question of whether the digital competences of the workforce is a research topic. The authors argue for the thesis that it is indeed a research topic. Design/methodology/approach In addition to a literature analysis of the top IS, HR, and learning publications, non-scientific sources, as well as the opinions of the authors, are included. The authors’ thesis is challenged through a debate of corresponding pros and cons. Findings The definition of digital competences lacks scientific depth. Focussing on the workforce is valid, as a “lifelong” perspective is not mandatory for research. Digital competence research is a multidisciplinary task to which the IS field can make a valuable contribution. Research limitations/implications Although relevant references are included, some aspects are mainly driven by the opinions of the authors. The theoretical implications encompass a call for a scientific definition of digital competences. Furthermore, scholars should focus on the competences of the workforce, including occupations, roles, or industries. The authors conclude by providing a first proposal of a research agenda. Practical implications The practical implications include the alignment of multiple stakeholders for the design of “digital” curricula and the integration by HR departments of the construct of digital competences, e.g. for compensation matters and job requirements. Originality/value This paper is one of very few contributions in the area of the digital competences of the workforce, and it presents a starting point for future research activities.

scholarly journals Strengthening the SSTC NRS Scientific and Technical Potential through Participation in the IAEA Coordinated Research Projects

2021 ◽  
pp. 5-13
Author(s):  
Yu. Balashevska ◽  
D. Gumenyuk ◽  
Iu. Ovdiienko ◽  
O. Pecherytsia ◽  
I. Shevchenko ◽  
...  
Keyword(s):  
Best Practices ◽  
Safety Assessment ◽  
Radiation Safety ◽  
Research Projects ◽  
Spent Fuel ◽  
Research Activities ◽  
Technical Potential ◽  
Technical Issues ◽  
Fuel Characterization ◽  
Definition Of

The State Scientific and Technical Center for Nuclear and Radiation Safety (SSTC NRS), a Ukrainian enterprise with a 29-year experience in the area of scientific and technical support to the national nuclear regulator (SNRIU), has been actively involved in international research activities. Participation in the IAEA coordinated research activities is among the SSTC NRS priorities. In the period of 2018–2020, the IAEA accepted four SSTC NRS proposals for participation in respective Coordinated Research Projects (CRPs). These CRPs address scientific and technical issues in different areas such as: 1) performance of probabilistic safety assessment for multi-unit/multi-reactor sites; 2) use of dose projection tools to ensure preparedness and response to nuclear and radiological emergencies; 3) phenomena related to in-vessel melt retention; 4) spent fuel characterization. This article presents a brief overview of the abovementioned projects with definition of scientific contributions by the SSTC NRS (participation in benchmarks, development of methodological documents on implementing research stages and of IAEA technical documents (TECDOC) for demonstration of best practices and results of research carried out by international teams).

Geostatistical approach for multi-scale seismic liquefaction risk assessment

2021 ◽  
Author(s):  
Rose Line Spacagna ◽  
Massimo Cesarano ◽  
Stefania Fabozzi ◽  
Edoardo Peronace ◽  
Attilio Porchia ◽  
...  
Keyword(s):  
Regional Scale ◽  
Morphological Characteristics ◽  
Predisposing Factors ◽  
Data Availability ◽  
Hazard Maps ◽  
Multi Scale ◽  
Seismic Liquefaction ◽  
Research Activities ◽  
Geostatistical Approach ◽  
Definition Of

<p>The Seismic Microzonation studies (SMs), promoted all over the Italian territory by the Department of Civil Protection, provide fundamental knowledge of the subsoil response in seismic conditions at the urban scale. Amplification phenomena related to lithostratigraphic and morphological characteristics, instabilities and permanent deformations activated by the earthquake, are highlighted in hazard maps produced at increasing reliability levels (level 1 to 3 of SM). In particular, zones prone to liquefaction instability are firstly identified following the predisposing factors, such as geological and geotechnical characteristics and seismicity. The robustness of the definition of these areas is strongly correlated to the availability and the spatial distribution of surveys. Moreover, the typology and quality of the investigations considerably influence the method of analysis and the degree of uncertainty of the results.</p><p>This work aims to establish an updated procedure of the actual SM guidelines and integrates recent research activities at different levels of SMs, to improve the hazard maps accuracy in terms of liquefaction susceptibility. For the scope, the case of the Calabria region in the south of Italy, well known for the high level of seismicity, was studied. At a regional scale, the base-level analysis was implemented for a preliminary assessment of the Attention Zones (AZ), potentially susceptible to liquefaction. The predisposing factors were implemented at a large scale, taking advantage of geostatistical tools to quantify uncertainties and filter inconsistent data. The regional-scale analysis allowed to highlight areas prone to liquefaction and effectively addressed the subsequent level of analysis. At a local scale, the quantitative evaluation of the liquefaction potential was assessed using simplified methods, integrating data from different survey types (CPT, SPT, Down-Hole, Cross-Hole, MASW) available in SM database. The definition of Susceptibility Zones (SZ) was provided considering additional indexes, combining the results obtained from different surveys typologies and quantifying the uncertainty due to the limited data availability with geostatistical methods. The analyses at the regional and municipality scale were matched with seismic liquefaction evidence, well documented in past seismic events. This multi-scale process optimises resource allocation to reduce the level of uncertainty for subsequent levels of analysis, providing useful information for land management and emergency planning.</p>

scholarly journals SGLT2 inhibition requires reconsideration of fundamental paradigms in chronic kidney disease, ‘diabetic nephropathy’, IgA nephropathy and podocytopathies with FSGS lesions

2020 ◽  
Author(s):  
Hans-Joachim Anders ◽  
Anna Julie Peired ◽  
Paola Romagnani
Keyword(s):  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Glucose Transporter ◽  
Immunoglobulin A ◽  
Adverse Outcomes ◽  
Glucose Transporter 2 ◽  
Research Activities ◽  
Background Therapy ◽  
Sglt2 Inhibition

Abstract In 2020, the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial first demonstrated that inhibition of the sodium–glucose transporter-2 (SGLT2) with dapagliflozin attenuates the progression of chronic kidney disease (CKD) with proteinuria in patients with or without diabetes at an unprecedented effect size. These results have far-reaching implications for a series of traditional concepts in Nephrology. It now became obvious that CKD with and without diabetes involves a predominant SGLT2-driven pathophysiology compared with the other pathogenic pathways currently under consideration. As SGLT2 inhibition is similarly efficacious in diabetic and non-diabetic CKD with proteinuria, treating CKD rather than ‘diabetic nephropathy’ becomes the central paradigm. Indeed, in older adults with type 2 diabetes, CKD is rather of multifactorial origin. As the DAPA-CKD trial included more patients with immunoglobulin A nephropathy (IgAN) than any of the previous IgAN trials, dual renin-angiotensin/SGLT2 inhibition may become the new standard. The same applies for patients with podocytopathy-related focal segmental glomerulosclerosis lesions. From now on, IgAN and podocytopathy trials without SGLT2 inhibition as background therapy and without glomerular filtration rate decline as primary outcome criterion will be of limited value. These and other potential implications will trigger broad discussions and secondary research activities with conclusions difficult to predict today. However, one is for sure: Nephrology after the DAPA-CKD trial will be not the same as it was before. Finally!

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