scholarly journals TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?

2019 ◽  
Vol 133 (10) ◽  
pp. 1145-1166 ◽  
Author(s):  
Stella Bernardi ◽  
Rebecca Voltan ◽  
Erika Rimondi ◽  
Elisabetta Melloni ◽  
Daniela Milani ◽  
...  

Abstract Ligands and receptors of the tumor necrosis factor (TNF) superfamily regulate immune responses and homeostatic functions with potential diagnostic and therapeutic implications. Kidney disease represents a global public health problem, whose prevalence is rising worldwide, due to the aging of the population and the increasing prevalence of diabetes, hypertension, obesity, and immune disorders. In addition, chronic kidney disease is an independent risk factor for the development of cardiovascular disease, which further increases kidney-related morbidity and mortality. Recently, it has been shown that some TNF superfamily members are actively implicated in renal pathophysiology. These members include TNF-related apoptosis-inducing ligand (TRAIL), its decoy receptor osteoprotegerin (OPG), and TNF-like weaker inducer of apoptosis (TWEAK). All of them have shown the ability to activate crucial pathways involved in kidney disease development and progression (e.g. canonical and non-canonical pathways of the transcription factor nuclear factor-kappa B), as well as the ability to regulate cell proliferation, differentiation, apoptosis, necrosis, inflammation, angiogenesis, and fibrosis with double-edged effects depending on the type and stage of kidney injury. Here we will review the actions of TRAIL, OPG, and TWEAK on diabetic and non-diabetic kidney disease, in order to provide insights into their full clinical potential as biomarkers and/or therapeutic options against kidney disease.

2019 ◽  
Vol 48 (1) ◽  
pp. 32-39
Author(s):  
Deidra C. Crews ◽  
Aminu K. Bello ◽  
Gamal Saadi ◽  

Kidney disease is a global public health problem, affecting over 750 million persons worldwide. The burden of kidney disease varies substantially across the world. In many settings, rates of kidney disease and the provision of its care are defined by socioeconomic, cultural, and political factors leading to significant disparities. World Kidney Day 2019 offers an opportunity to raise awareness of kidney disease and highlight disparities in its burden and current state of global capacity for prevention and management. Here, we highlight the need for strengthening basic infrastructure for kidney care services for early detection and management of acute kidney injury and chronic kidney disease across all countries and advocate for more pragmatic approaches to providing renal replacement therapies. Achieving universal health coverage worldwide by 2030 is a World Health Organization Sustainable Development Goal. While universal health coverage may not include all elements of kidney care in all countries, understanding what is locally feasible and important with a focus on reducing the burden and consequences of kidney disease would be an important step towards achieving kidney health equity.


2018 ◽  
Vol 34 (11) ◽  
pp. 1853-1863 ◽  
Author(s):  
Ruifeng Wang ◽  
Titi Chen ◽  
Chengshi Wang ◽  
Zhiqiang Zhang ◽  
Xin Maggie Wang ◽  
...  

Abstract Background Chronic kidney disease (CKD) is a global public health problem, which lacks effective treatment. Previously, we have shown that CD103+ dendritic cells (DCs) are pathogenic in adriamycin nephropathy (AN), a model of human focal segmental glomerulosclerosis (FSGS). Fms-like tyrosine kinase 3 (Flt3) is a receptor that is expressed with high specificity on tissue resident CD103+ DCs. Methods To test the effect on CD103+ DCs and kidney injury of inhibition of Flt3, we used a selective Flt3 inhibitor (AC220) to treat mice with AN. Results Human CD141+ DCs, homologous to murine CD103+ DCs, were significantly increased in patients with FSGS. The number of kidney CD103+ DCs, but not CD103− DCs or plasmacytoid DCs, was significantly decreased in AN mice after AC220 administration. Treatment with AC220 significantly improved kidney function and reduced kidney injury and fibrosis in AN mice. AC220-treated AN mice had decreased levels of inflammatory cytokines and chemokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, CCL2 and CCL5 and reduced kidney infiltration of CD4 T cells and CD8 T cells. The protective effect of AC220 was associated with its suppression of CD103+ DCs-mediated CD8 T cell proliferation and activation in AN mice. Conclusion Flt3 inhibitor AC220 effectively reduced kidney injury in AN mice, suggesting that this inhibitor might be a useful pharmaceutical agent to treat CKD.


2013 ◽  
Vol 154 (2) ◽  
pp. 43-51 ◽  
Author(s):  
Judit Nagy

Chronic kidney disease is a general term for heterogenous disorders with >3 months duration affecting kidney structure and function. Nowadays, involving 10–16% of the adult population worldwide, chronic kidney disease is recognised as a major global public health problem. The number of cases is continuously increasing. In this review, epidemiology, definition, new classification and a conceptual model for development, progression and complications of chronic kidney disease as well as strategies to improve outcome are summarized. Orv. Hetil., 2013, 154, 43–51.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tosin Opadokun ◽  
Petra Rohrbach

AbstractMalaria is a complex parasitic disease, caused by Plasmodium spp. More than a century after the discovery of malaria parasites, this disease continues to pose a global public health problem and the pathogenesis of the severe forms of malaria remains incompletely understood. Extracellular vesicles (EVs), including exosomes and microvesicles, have been increasingly researched in the field of malaria in a bid to fill these knowledge gaps. EVs released from Plasmodium-infected red blood cells and other host cells during malaria infection are now believed to play key roles in disease pathogenesis and are suggested as vital components of the biology of Plasmodium spp. Malaria-derived EVs have been identified as potential disease biomarkers and therapeutic tools. In this review, key findings of malaria EV studies over the last 20 years are summarized and critically analysed. Outstanding areas of research into EV biology are identified. Unexplored EV research foci for the future that will contribute to consolidating the potential for EVs as agents in malaria prevention and control are proposed.


2011 ◽  
Vol 12 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Americo Cicchetti ◽  
Matteo Ruggeri ◽  
Paola Codella ◽  
Alessandro Ridolfi

Chronic kidney disease is growing as a global public health problem throughout the world. In Italy, CKD is becoming increasingly common with 52,777 patients treated with dialysis in 2010, about 10,000 new patients/years in dialysis from 2010.  The impact on the health care system includes € 2.1 billion/year for dialysis plus € 338 million for indirect costs. Aim of the present analysis was to explore socio-economical variables in the management of CKD, and assess direct and indirect health costs and NHS resources consumption. The overall cost for patients in dialysis is about 44,000 €/years for hemodialysis and 30,000 €/years for peritoneal dialysis with different resources consumption over the different stage disease. The possibility of reducing the progression of renal damaging and beginning of dialysis may induce a low expenditure for the Italian NHS.


2019 ◽  
Vol 49 (3) ◽  
pp. 254-262 ◽  
Author(s):  
Deidra C. Crews ◽  
Aminu K. Bello ◽  
Gamal Saadi ◽  

Kidney disease is a global public health problem, affecting over 750 million persons worldwide. The burden of kidney disease varies substantially across the world. In many settings, rates of kidney disease and the provision of its care are defined by socioeconomic, cultural, and political factors leading to significant disparities. World Kidney Day 2019 offers an opportunity to raise awareness of kidney disease and highlight disparities in its burden and current state of global capacity for prevention and management. Here, we highlight the need for strengthening basic infrastructure for kidney care services for early detection and management of acute kidney injury and chronic kidney disease across all countries and advocate for more pragmatic approaches to providing renal replacement therapies. Achieving universal health coverage worldwide by 2030 is a World Health Organization Sustainable Development Goal. While universal health coverage may not include all elements of kidney care in all countries, understanding what is locally feasible and important with a focus on reducing the burden and consequences of kidney disease would be an important step towards achieving kidney health equity.


2019 ◽  
Vol 19 (8) ◽  
pp. 567-578 ◽  
Author(s):  
Marcus Vinicius Nora de Souza ◽  
Thais Cristina Mendonça Nogueira

Nowadays, tuberculosis (TB) is an important global public health problem, being responsible for millions of TB-related deaths worldwide. Due to the increased number of cases and resistance of Mycobacterium tuberculosis to all drugs used for the treatment of this disease, we desperately need new drugs and strategies that could reduce treatment time with fewer side effects, reduced cost and highly active drugs against resistant strains and latent disease. Considering that, 4H-1,3-benzothiazin-4-one is a promising class of antimycobacterial agents in special against TB-resistant strains being the aim of this review the discussion of different aspects of this chemical class such as synthesis, mechanism of action, medicinal chemistry and combination with other drugs.


2021 ◽  
Vol 22 (9) ◽  
pp. 4480
Author(s):  
Maria Tziastoudi ◽  
Georgios Pissas ◽  
Georgios Raptis ◽  
Christos Cholevas ◽  
Theodoros Eleftheriadis ◽  
...  

Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. In an effort to elucidate the contribution of genetic variants located in several genes in the response to treatment of patients with CKD, we performed a systematic review and meta-analysis of all available pharmacogenetics studies. The association between genotype distribution and response to medication was examined using the dominant, recessive, and additive inheritance models. Subgroup analysis based on ethnicity was also performed. In total, 29 studies were included in the meta-analysis, which examined the association of 11 genes (16 polymorphisms) with the response to treatment regarding CKD. Among the 29 studies, 18 studies included patients with renal transplantation, 8 involved patients with nephrotic syndrome, and 3 studies included patients with lupus nephritis. The present meta-analysis provides strong evidence for the contribution of variants harbored in the ABCB1, IL-10, ITPA, MIF, and TNF genes that creates some genetic predisposition that reduces effectiveness or is associated with adverse events of medications used in CKD.


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