Regulation of Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κβ) in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD), encompassing both Crohn Disease (CD) and ulcerative colitis (UC) are globally prevalent diseases, impacting children of all ages. The hallmark of IBD is a perturbed immune system that leads to continuous inflammation in the gut and challenges optimal treatment. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), a nuclear transcription factor, plays a major role in gut homeostasis and contributes significantly toward a balanced, homeostatic immune system. Dysregulation in the NF-κβ pathway and factors that regulate it lead to a state of uncontrolled inflammation and altered immunity, as typically observed in IBD. Levels of proinflammatory cytokines that are regulated through NF-κβ are increased in both CD and UC. Genes known to activate NF-κβ, such as, Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and Interleukin 23 (IL-23), are associated with IBD. Factors involved in inhibition of NF-κβ, such as A20 and TOLLIP, are also affected in IBD, resulting in failed inflammation suppression/regulation. NOD-2 and A20 have specifically been found to be strongly associated with pediatric IBD. Gut commensals are known to exert anti-inflammatory activities toward NF-κβ and can have a potential role in attenuating inflammation that likely occurs due to microbial dysbiosis in IBD. Failure to terminate/downregulate NF-κβ signaling results in chronic inflammation in IBD. Well-regulated control of inflammation in children with IBD can help better control the disease and suppress immune responses. Better understanding of factors that control NF-κβ can potentially lead toward discovering targeted therapeutic interventions for IBD. Suppression of NF-κβ can be achieved through many modalities including anti-sense oligonucleotides (ASOs), siRNA (small interfering RNA), factors regulating NF-κβ, and microbes. This review focuses on the role of NF-κβ, especially in pediatric IBD, and potential therapeutic venues for attenuating NF-κβ-induced inflammation

Availability and prioritisation of COVID-19 vaccines among patients with advanced chronic kidney disease and kidney failure during the height of the pandemic: a global survey by the International Society of Nephrology

OBJECTIVE Patients with advanced chronic kidney disease (CKD) or kidney failure receiving replacement therapy (KFRT) are highly vulnerable to COVID-19 infection, morbidity and mortality. Vaccination is effective, but access differs around the world. We aimed to ascertain the availability, readiness and prioritisation of COVID-19 vaccines for this group of patients globally. SETTING AND PARTICIPANTS Collaborators from the International Society of Nephrology (ISN), Dialysis Outcomes and Practice Patterns Study and ISN-Global Kidney Health Atlas developed an online survey that was administered electronically to key nephrology leaders in 174 countries between 2 July and 4 August 2021. RESULTS Survey responses were received from 99 of 174 countries from all 10 ISN regions, among which 88/174 (50%) were complete. At least one vaccine was available in 96/99 (97%) countries. In 71% of the countries surveyed, patients on dialysis were prioritised for vaccination, followed by patients living with a kidney transplant (KT) (62%) and stage 4/5 CKD (51%). Healthcare workers were the most common high priority group for vaccination. At least 50% of patients receiving in-centre haemodialysis, peritoneal dialysis or KT were estimated to have completed vaccination at the time of the survey in 55%, 64% and 51% of countries, respectively. At least 50% of patients in all three patient groups had been vaccinated in >70% of high-income countries and in 100% of respondent countries in Western Europe.The most common barriers to vaccination of patients were vaccine hesitancy (74%), vaccine shortages (61%) and mass vaccine distribution challenges (48%). These were reported more in low-income and lower middle-income countries compared with high-income countries. CONCLUSION Patients with advanced CKD or KFRT were prioritised in COVID-19 vaccination in most countries. Multiple barriers led to substantial variability in the successful achievement of COVID-19 vaccination across the world, with high-income countries achieving the most access and success

A roadmap for kidney care in Africa: An analysis of International Society of Nephrology–Global Kidney Health Atlas Africa data describing current gaps and opportunities

Delivery of kidney care in Africa is significantly constrained by various factors. In this review, we used International Society of Nephrology–Global Kidney Health Atlas (ISN–GKHA) data for Africa to address sub-regional differences in care delivery in the continent with focus on infrastructure, workforce, and the economic aspects of kidney care. Forty two African countries participated in the survey conducted in 2018. North Africa had the highest proportions of nephrologists [12.53 per million population (pmp)], nephrology trainees (2.19 pmp) and haemodialysis (HD) centres (8.58 pmp); whereas southern Africa had the highest proportions of peritoneal dialysis (PD) centres (0.89 pmp) and kidney transplant (KT) centres (0.29 pmp); West Africa had the greatest nephrology workforce shortages. The annual median costs of HD (US$22,731 [interquartile range (IQR): US$1,560–43,902]) and PD (US$34,165 [US$34,165–34,165]) were highest in Central Africa and only Algeria, Egypt and South Africa reported zero co-payment for all modalities of kidney replacement therapy in the public sector. Policies on chronic kidney disease and non-communicable diseases were scarcely available across all African sub-regions. The ISN–GKHA African data highlight a stark difference in kidney care measures between North and sub-Saharan Africa and also suggest the need for a more cohesive approach to policy formulations that support and protect patients with kidney disease in the continent, especially from the excessive costs associated with care. Using the World Health Organization (WHO) Global Action Plan for noncommunicable diseases, this paper proposes an African roadmap for optimal kidney care

Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis

Background Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population. Methods/design We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran’s Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity). Discussion Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD. Systematic review registration PROSPERO registration number: [ CRD42020206514 ]

Impact of home telemonitoring and management support on blood pressure control in non-dialysis CKD: a systematic review protocol

Introduction Hypertension is a common public health problem and a key modifiable risk factor for cardiovascular (CV) and chronic kidney disease (CKD). Home blood pressure (BP) telemonitoring (HBPT) and management is associated with improved BP control, accelerated delivery of care and decision-making strategies that can reduce adverse outcomes associated with hypertension. The aim of this paper is to describe the protocol for a systematic review to assess the impact of HBPT interventions used for improving BP control and reducing CV and kidney outcomes in non-dialysis CKD patients.Methods We developed this protocol using the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science and PsycINFO and grey literature for studies conducted in non-dialysis CKD patients on interventions using HBPT and reporting outcomes related to BP control and other outcomes such as CV events and kidney disease progression. All studies meeting these criteria, in adults and published from inception until 2020 with no language barrier will be included.Ethics and dissemination Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of HBPT on BP control in non-dialysis CKD patients, evidence gathered through it will be disseminated using traditional approaches that includes open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate government agencies.PROSPERO registration number CRD42020190705)