Kidney Disease Research Articles

Ten years trajectories of estimated glomerular filtration rate (eGFR) in a multiethnic cohort of people with type 1 diabetes and preserved renal function

ObjectivesWe aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m2.DesignObservational...

Cerebral white matter damage in patients with end stage kidney disease associates with cognitive impairment

Abstract Background and hypothesis Damages in brain white matter often occurs in individuals with chronic kidney disease, which might be related to their cognitive decline. This study aims to investigate tract specific white matter damage in patients with end stage renal disease by using fixel based analysis. Methods Images of 31 end stage renal disease patients and 16 normal controls (aged: 61.1 ± 10.4 years; 11 men) were acquired from a 1.5 T MR scanner. The patients were subsequently divided into with normal cognition (N = 17, aged: 66.9 ± 7.2 years; 10 men) and cognitive impairment (N = 14, aged: 72.4 ± 9.4 years; 7 men). Cognitive assessment, neurologic, hematologic and biochemical samples were collected. Fixel-based analysis was used to examine the tract-specific damage within white matter. Differences between groups were evaluated through connectivity-based fixel enhancement and non-parametric permutation testing. Correlation with biomarkers was conducted through general linear model. Significance was determined with familywise error-corrected p-value < 0.05. Results Reduced fixel-based metrics were observed in specific tract located the cerebral peduncle, internal capsule, corpus callosum, fornix, and superior corona radiata in patients when compared to normal controls, indicating a reduction in fiber content. The fibers crossing the corpus callosum and the fornix/stria terminalis are particularly vulnerable sites, which can be associated with the decrease in both Mini-Mental State Examination (R2 ranged between 0.420 and 0.556) and Montreal Cognitive Assessment (R2 ranged between 0.425 and 0.509), as well as the plasma concentration of calcium (R2 ranged between 0.207 and 0.322). The plasma concentration of indoxyl sulfate was associated with the descending tracts from right posterior limb of internal capsule to cerebral peduncle (R2 ranged between 0.262 and 0.335). Conclusions Tract specific white matter damage can be noticed in the patients with end stage renal disease, and can be associated with their cognitive decline.

Annual variation of estimated glomerular filtration rate in health check-ups associated with end-stage kidney disease

Estimated glomerular filtration rate (eGFR) variation is associated with end-stage kidney disease (ESKD) development in patients with chronic kidney disease; whether annual variations in eGFR at health check-ups is associated with ESKD risk in the general population is unclear. We conducted a retrospective cohort study using Japanese national medical insurance claims from 2013 to 2020. Individuals who had their eGFR levels measured three times in annual health check-ups were included (N = 115,191), and the coefficient of variation of eGFR (CVeGFR) was calculated from 3-point eGFR. The end-point was ESKD as reported in the claims data. We analyzed the association between CVeGFR and ESKD incidence after adjusting for conventional ESKD risk factors. The CVeGFR median distribution was 5.7% (interquartile range: 3.5–8.5%). During a median follow-up period of 3.74 years, 164 patients progressed to ESKD. ESKD incidence was significantly higher in the highest quartile group (CVeGFR ≥ 8.5%) than in the other groups (P < 0.0001). After adjusting for risk factors, individuals with CVeGFR ≥ 8.5% had a significantly high ESKD incidence (adjusted hazard ratio: 3.01; 95% CI 2.14–4.30). High CVeGFR in annual health check-ups was associated with high ESKD incidence, independent of its other conventional risk factors, in the general population.

Validated Administrative Data-Based ICD-10 Algorithms for Chronic Conditions

ObjectiveThis systematic review aimed to identify ICD-10 based validated algorithms for chronic conditions using health administrative data. MethodsA comprehensive systematic literature search using Ovid MEDLINE, Embase, PsycINFO, Web of Science and CINAHL was performed to identify studies, published between 1983 and May 2023, on validated algorithms for chronic conditions using administrative health data. Two reviewers independently screened titles and abstracts and reviewed full text of selected studies to complete data extraction. A third reviewer resolved conflicts arising at the screening or study selection stages. The primary outcome was validated studies of ICD-10 based algorithms with both sensitivity and PPV of ≥70%. Studies with either sensitivity or PPV &lt;70% were included as secondary outcomes. ResultsOverall, the search identified 1686 studies of which 55 met the inclusion criteria. Combining a previously published literature search, a total of 61 studies were included for data extraction. Of these, 30 studies demonstrated algorithms with high validity and 30 showed moderate validity. Studies with highly valid algorithms were based on administrative data from different countries including Canada, USA, Australia, Japan, France, South Korea, and Taiwan. Validated algorithms with PPV and sensitivity of ≥70% were identified for more than 40 chronic conditions that included several types of cancers, cardiovascular conditions, kidney diseases, gastrointestinal disorders, and peripheral vascular diseases, amongst others. ConclusionWith ICD-10 prominently used across the world, this up-to-date systematic review can prove to be a helpful resource for research and surveillance initiatives using administrative health data for identifying chronic conditions.

Balancing Privacy and Precision: Evaluating Meta-Analysis for National Health Data Integration in Canada

BackgroundIn Canada, legislative restrictions exist for the disclosure and transfer of patient data across provincial boundaries. Often, meta-analysis techniques are employed to pool province-specific results to enable national results while maintaining compliance with privacy legislation. However, the effectiveness of this technique remains unexamined using electronic data. To evaluate its performance, we compare results obtained through meta-analysis with those from a fully pooled model. MethodsUsing chronic kidney disease as a case study, this retrospective cohort study simulates the meta-analysis method to evaluate its performance using real data. We analyze data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), a nationwide database of electronic medical records. We meta-analyze provincial logistic regression models to predict nephropathy over a 5-year period at a national level. Estimates are compared to a fully pooled national model. ResultsAnalyses are currently ongoing. We expect the meta-analysis technique to produce similar estimates compared to the fully pooled model. However, we expect certain differences as meta-analysis techniques are insensitive to heterogeneity within provinces that impact the precision of estimates. Observed differences will help to inform future work where we will examine a potential new methodology to analyze health information without sharing patient data. ConclusionsBased on our results, we will reveal strengths and limitations of the meta-analysis technique for interprovincial analyses. Limitations of the meta-analysis technique may underscore the need for further exploration into alternative methodologies that can effectively analyze health information without compromising patient privacy to facilitate better healthcare decision-making and policy development in Canada.

Homelessness and Kidney Disease—Time for Action

Homelessness and Kidney Disease—Time for Action

Increasing MicroRNA Abundance by Targeting Biogenesis from the Primary Transcript with Steric-Blocking Antisense Oligonucleotides.

MicroRNAs (miRNAs) are regulators of gene expression, and their dysregulation is linked to cancer and other diseases, making them important therapeutic targets. Several strategies for targeting and modulating miRNA activity are being explored. For example, steric blocking antisense oligonucleotides (ASOs) can reduce miRNA activity by either blocking binding sites on specific mRNAs or base-pairing to the miRNA itself to prevent its interaction with the target mRNAs. ASOs have been less explored as a tool to elevate miRNA levels, which could also be beneficial for treating disease. In this study, using the PKD1/miR-1225 gene locus as an example, where miR-1225 is located within a PKD1 intron, we demonstrate an ASO-based strategy that increases miRNA abundance by enhancing biogenesis from the primary miRNA transcript. Disruptions in PKD1 and miR-1225 are associated with autosomal dominant polycystic kidney disease (ADPKD) and various cancers, respectively, making them important therapeutic targets. We investigated PKD1 sequence variants reported in ADPKD that are located within the sequence shared by miR-1225 and PKD1, and identified one that causes a reduction in miR-1225 without affecting PKD1. We show that this reduction in miR-1225 can be recovered by treatment with a steric-blocking ASO. The ASO-induced increase in miR-1225 correlates with a decrease in the abundance of predicted miR-1225 cellular mRNA targets. This study demonstrates that miRNA abundance can be elevated using ASOs targeted to the primary transcript. This steric-blocking ASO-based approach has broad potential application as a therapeutic strategy for diseases that could be treated by modulating miRNA biogenesis.

Sarcopenia in the era of precision health: Towards personalized interventions for healthy longevity.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, significantly impacts health outcomes in older adults. This review explores the evolving landscape of sarcopenia research, with a particular focus on its unique characteristics in Asian populations and emerging pharmaceutical interventions. Recent studies have revealed distinct patterns of muscle mass decline in Asian adults, particularly in women, challenging the universal application of global sarcopenia diagnostic criteria. The Asian Working Group for Sarcopenia has proposed region-specific diagnostic criteria, acknowledging these ethnic variations. Prevalence estimates of sarcopenia vary widely, ranging from 10% to 40% in community-dwelling older adults. For specific chronic conditions, the prevalence of sarcopenia is notably higher, reaching 35% for cardiovascular diseases and 24.5% for chronic kidney disease. Sarcopenia is strongly associated with various chronic conditions, increasing the risk of falls by 1.5-3 times and significantly increasing mortality risk by 29-51%. Current management strategies primarily involve resistance exercise and nutritional interventions, with a recommended daily protein intake of at least 1.2 g/kg to maintain muscle health. Pharmaceutical development has gained significant momentum, with over 20 compounds in various stages of clinical trials. These include myostatin inhibitors, selective androgen receptor modulators, ghrelin receptor agonists, mesenchymal stem cell therapy and follistatin gene therapy. However, the unique dietary patterns, cultural contexts, and potentially distinct drug responses in Asian populations necessitate tailored interventions and Asia-specific clinical trials. Future directions include refining Asian-specific diagnostic criteria, conducting large-scale epidemiological studies across multiple Asian countries, developing culturally appropriate interventions, integrating sarcopenia management into chronic disease care, and advancing pharmaceutical research with a focus on Asian populations. In conclusion, sarcopenia emerges as a critical nexus in the aging process, intricately linked with multiple organ systems and chronic conditions, underscoring the imperative for its recognition as a cornerstone in person-centered care and the holistic management of age-related health challenges.

Adverse childhood experiences and multimorbidity of internalising and cardiometabolic conditions in an older-age population.

BackgroundTackling multimorbidity (ICM-MM) of internalising conditions (IC) and cardiometabolic conditions (CM) is key to improving the future of healthcare. Early life factors such as adverse childhood experiences (ACEs) have been linked to long term, poor mental and physical health conditions. AimsThis study investigated whether: 1) ACEs increase the risk of IC, CM and ICM-MM; 2) the effect of ACEs on risk of developing CM depends on the presence of IC and vice versa; 3) how risk differs by gender, socioeconomic status and ethnicity. MethodsIn UK Biobank, the Childhood Trauma Screener was used to identify 157,256 participants with ACE data. Electronic healthcare records (EHR) and interview data identified those with anxiety or depression (IC) and those with hypertension, obesity, type 2 diabetes, dyslipidaemia or chronic kidney disease (CM). Multivariate logistic regression models were employed to find associations between ACEs and IC, CM and ICM-MM. Covariates included age, gender, ethnicity, socioeconomic status, diet, alcohol intake, smoking behaviour and physical activity. ResultsAll ACEs significantly increase risk for IC (all ACEs, p = &lt;2e-16). Emotional neglect, physical neglect and emotional abuse increase risk of CM (e.g. physical neglect, OR = 1.43, CF = 1.30-1.58, p = 1.88e-13). ACEs appear to increase IC and CM risk independently. ConclusionsThe effects of ACEs last well into adulthood and confer risk for IC and, sometimes, CM. ACE history should be included in routine primary care and the development of therapeutic interventions tailored to older adults with ACEs is key to reducing poor health.

Association of pulse pressure with incident end-stage kidney disease according to histopathological kidney findings in patients with diabetic nephropathy.

Diabetic patients as well as the elderly are known to have high pulse pressure (PP), but there are few studies on how microangiopathy and macroangiopathy are involved in its mechanism. In this study, we examined the association between PP and atherosclerotic lesions by vessel size in kidney biopsy tissue and examined how PP is associated with kidney prognosis. This retrospective observational study included 408 patients with biopsy-proven diabetic nephropathy at Nara Medical University Hospital. Exposure of interest was PP measured at kidney biopsy. Outcome variable was kidney failure with replacement therapy (KFRT). Cox proportional hazards and competing risk regression models with all-cause mortality as a competing event were used to examine these associations. A total of 408 patients were divided into tertiles based on PP (mmHg): Tertile 1 (reference), <51; Tertile 2, 51-64; and Tertile 3, >64. Among the 408 patients, 99 developed KFRT during a median follow-up period of 6.7 years. Higher PP was independently associated with higher incidences of KFRT (hazard ratio [95% confidence interval] for Tertile 3 vs. Tertile 1; 2.07 [1.05-4.09]. In histological lesions, PP was strongly associated with glomerular lesions, tubulointerstitial lesions, and arteriolar hyalinosis (all ps for trend <0.001), but not with intimal thickening (p for trend = 0.714). PP was significantly associated with diabetic glomerular/tubulointerstitial lesions and arteriolar hyalinosis but not with intimal thickening at the time of kidney biopsy and was also significantly associated with subsequent KFRT in patients with diabetic nephropathy.

Modelling The Effects of Multi-Indication Treatment for Multiple Long-Term Conditions Using Population-Scale Linked Electronic Health Records To Inform Healthcare Policy

Background and ObjectivesHealthcare decision-making has previously focused on developing recommendations for single conditions. This research aimed to develop a modeling framework to estimate the effects of multi-indication treatment in people living with multiple long-term conditions. ApproachUsing a case study in type 2 diabetes mellitus [T2DM], chronic kidney disease [CKD], and heart failure [HF], age-adjusted multistate models were used to estimate the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors as a multi-indication treatment. Baseline hazards were estimated using population-scale, individual-level, linked anonymized electronic health record (EHR) data for 613,195 individuals aged 55 to 85 years in Wales over a 20-year period. Hazard ratios for treatment effects compared to standard of care were obtained from randomized controlled trials for combinations of multiple-long term conditions and incorporated in a patient-level simulation. ResultsSGLT2 inhibitors increased the estimated mean life expectancy from 0.02 (95% Confidence Interval (CI): -0.02, 0.05) to 1.44 (95% CI: 1.12, 1.74) years in people living with coexisting T2DM, CKD, and HF. The estimated gain in life expectancy was less than 0.5 years for individuals with T2DM, CKD, and HF in different temporally ordered sequences. The estimated mean time to develop HF increased by 3.1 (95% CI: 3.00, 3.24) and 1.34 (95% CI: 1.12, 1.56) years in individuals with CKD, and in those with CKD followed by T2DM. Conclusions and ImplicationsThere is an ever increasing need to appraise interventions in people living with multiple long-term conditions to identify optimal treatment strategies and reduce polypharmacy. Multistate models applied to linked EHRs allow for a more rigorous assessment of treatment effects to inform healthcare policy.

Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease

To explore the clinical phenotype and genetic etiology for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease (ADPKD). A pedigree with ADPKD diagnosed at the Department of Gynaecology of the First Affiliated Hospital of Zhengzhou University in December 2020 was selected as the study subject. Clinical data of the pedigree was collected, and whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the proband and her relatives. Fetal ultrasonography showed increased volume and parenchymal echogenicity in both kidneys. The fetus was found to harbor c.11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene, which were respectively inherited from its mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1+PM2_supporting+PP3). The c.11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene probably underlay the ADPKD in the fetus. Above finding has provided guidance for the genetic counseling and prenatal diagnosis for this pedigree.

Improving reproducibility and validity in measures of chronic disease incidence using large-scale linked data in Australia.

Objective and ApproachOur study aimed to improve methods for identifying incident chronic kidney disease (CKD), cardiovascular disease (CVD), and diabetes in a young cohort from the Antecedents of Renal Disease in Aboriginal Children (ARDAC) study. We linked 20 state and federal administrative health datasets, including hospital records, Medicare claims, pharmaceutical data, and the National Diabetes Services Scheme (NDSS) data for the first time. This approach facilitated the development of new algorithms for disease detection. Notably, we will make the R code for these algorithms publicly available. ResultsThe analysis, involving 3,758 ARDAC study participants, created clinically robust definitions of CKD, CVD, and diabetes (by subtype) in the Australian linked data context; and revealed that all other data sources inaccurately estimated the incidence of diabetes compared to the NDSS data. ConclusionsThis key finding illustrates the discrepancy in diabetes incidence estimates and highlights the value of integrating multiple data sources for the investigation of chronic disease. ImplicationsHundreds of published studies use data linkage to investigate CVD, CKD, and diabetes in the Australian context. Our novel robust case definitions, and the identified poor estimation of diabetes incidence among young people, underscores the need to critically evaluate linked data sources used to inform health policy and research. By sharing the developed R code, we support ongoing efforts to improve transparency and replicability in health research. Our study refines chronic disease definition methods and contributes to more effective public health strategies, with particular focus on improving outcomes for Indigenous communities.

Perioperative outcomes of 105 cases of ABO-incompatible live donor kidney transplantation: a retrospective single-center observational study.

ABO-incompatible (ABOi) kidney transplantation poses significant challenges in achieving successful outcomes. This study aimed to investigate the impact of various interventions and techniques on improving the success rates of ABOi kidney transplantation. We conducted a retrospective observational analysis of patients who underwent ABOi kidney transplantation from November 2012 to March 2023. The study included a total of 105 patients. We collected and analyzed data on patient demographics, preoperative assessments, surgical details, and postoperative outcomes. The mean ages of the donors and recipients were 50.52±10.32 and 36.63±11.61 years, respectively. The majority of recipients were male (81.9%), while most donors were female (89.5%). The most common blood group among recipients was O (69.5%), and among donors, it was B (46.7%). The median durations of chronic kidney disease and dialysis were 12 months (interquartile range [IQR], 7-28 months) and 6 months (IQR, 2-12 months), respectively. Baseline antibody titers (anti-A and anti-B) ranged from 64.0 to 256.0, while on the day of surgery, they were ≤8. Perioperative complications included hypotension (10.5%), acute tubular necrosis (5.7%), delayed graft function (3.8%), and reexploration (3.8%) due to hematoma. ABOi kidney transplantation is a viable option for recipients lacking available donors with an ABO-compatible match. Perioperative concerns, including hypoalbuminemia, heightened risk of infections, coagulopathies, aseptic precautions, and immunological surveillance, must be carefully addressed.

Shared decision-making in end-of-life care for end-stage renal disease patients: nephrologists’ views and attitudes

BackgroundThe term end-stage renal disease (ESRD) refers to the final stage of chronic kidney disease. Not all ESRD patients are suitable for dialysis treatment, which despite its advantages, is not without risks. Shared nephrologist-patient decision-making could be beneficial at this stage, yet little is known about such practices in Israel. This study aimed at examining the practice of shared decision-making (SDM) between nephrologists and ESRD patients in Israel, while exploring related conflicts, ethical dilemmas, and considerations.MethodsThe descriptive-quantitative approach applied in this study included a validated questionnaire for nephrologists, based on Emanual and Emanual (1992). The survey, which was distributed via social-media platforms and snowball sampling, was completed by 169 nephrologists. Data analysis included t-tests for independent samples, f-tests for analysis of variance, and t-tests and f-tests for independence. Descriptive analysis examined attitudes towards SDM in end-of-life care for ESRD patients.ResultsThe findings show that the research sample did not include nephrologists who typically act according to the paternalistic decision-making style. Rather, 53% of the respondents were found to act in line with the informative decision-making style, while 47% act according to the interpretive decision-making style. Almost 70% of all respondents reported their discussing quality-of-life with patients; 63.4% provide prognostic assessments; 61.5% inquire about the patient’s desired place of death; 58.6% ask about advance directives or power-of-attorney; and 57.4% inquire about cultural and religious beliefs in end-of-life treatment. Additionally, informative nephrologists tend to promote the patients’ autonomy over their health (P < 0.001); they are also in favor of conservative treatment, compared to paternalistic and interpretive nephrologists, and use less invasive methods than other nephrologists (P = 0.02).ConclusionsNephrologists in Israel only partially pursue an SDM model, which has the potential to improve quality-of-care for ESRD patients and their families. SDM programs should be developed and implemented for increasing such practices among nephrologists, thereby expanding the possibilities for providing conservative care at end-of-life.

The Role of Polycystic Kidney Disease-like Homologs in planarian Nervous System Regeneration and Function

Abstract Planarians are an excellent model for investigating molecular mechanisms necessary for regenerating a functional nervous system. Numerous studies have led to the generation of extensive genomic resources, especially whole-animal single-cell RNA-seq resources. These have facilitated in silico predictions of neuronal subtypes, many of which have been anatomically mapped by in situ hybridization. However, our knowledge of the function of dozens of neuronal subtypes remains poorly understood. Previous investigations identified that polycystic kidney disease (pkd)-like genes in planarians are strongly expressed in sensory neurons and have roles in mechanosensation. Here, we examine the expression and function of all the pkd genes found in the Schmidtea mediterranea genome and map their expression in the asexual and hermaphroditic strains. Using custom behavioral assays, we test the function of pkd genes in response to mechanical stimulation and in food detection. Our work provides insight into the physiological function of sensory neuron populations and protocols for creating inexpensive automated setups for acquiring and analyzing mechanosensory stimulation in planarians.

Impact of Cardio-Ankle Vascular Index on Future Cancer in Patients With Coronary Artery Disease.

Cardiovascular risk factors are associated with increased risk of future cancer. However, the relationship between quantitative parameters of atherosclerosis and future cancer risk is unclear. A total of 1,057 consecutive patients with coronary artery disease was divided into 2 groups according to the cutoff value of the cardio-ankle vascular index (CAVI) derived by receiver operating characteristic curve analysis: low CAVI group (CAVI <8.82; n=487), and high CAVI group (CAVI ≥8.82; n=570). Patients in the high CAVI group were older and had a higher prevalence of diabetes, chronic kidney disease, anemia and history of stroke compared with patients in the low CAVI group. There were 141 new cancers during the follow-up period. The cumulative incidence of new cancer was significantly higher in the high CAVI group than in the low CAVI group (P=0.001). In a multivariate Cox proportional hazard analysis, high CAVI was found to be an independent predictor of new cancer diagnosis (hazard ratio 1.62; 95% confidence interval 1.11-2.36; P=0.012). In the analysis of individual cancer types, high CAVI was associated with lung cancer (hazard ratio 2.85; 95% confidence interval 1.01-8.07; P=0.049). High CAVI was associated with the risk of future cancer in patients with coronary artery disease.

Budget impact analysis on the Italian healthcare system of roxadustat for the treatment of anemia due to chronic kidney disease

Objective: The aim of this study was to evaluate the economic consequences of the introduction of roxadustat on the market as treatment for chronic kidney disease (CKD)-related anaemia in Italy. Method: A budget impact model was developed to assess the economic impact of the introduction of roxadustat for the management of patient with CKD-related anaemia. The analysis was conducted considering National Health Service (NHS) perspective and three years’ time horizon. Eligible population for the treatment with roxadustat was estimated through published literature and clinicians’ support. Direct healthcare costs included drug acquisition (list prices for base case) and administration costs, monitoring costs, cost per blood transfusion, costs related to the management of adverse events and dialysis costs. Results: The model estimated a three years expenditure associated with the management of patients with CKD-related incident anaemia in Italy of about € 260 and € 44.6 million for non-dialysis dependent (NDD) and dialysis-dependent (DD) patients respectively. The introduction of roxadustat on the market could generate a reduction in the expenditure related to the iron supplementation both for NDD and for DD patients (−€ 397,305 and −€ 50,135 over three years of the analysis, respectively) and a reduction in the pharmaceutical expenditure for NDD patients (−€ 2.3 million, −€ 7.5 million and −€ 13 million at first, second and third year of the analysis). Overall, the introduction of roxadustat could generate a saving for NHS approximately equal to € 2.3, € 7.5 and € 13 million at first, second and third year of the analysis. Conclusion: The introduction of roxadustat could generate a reduction in the expenditure for the management of patients with CKD anaemia. A scenario analysis which used tender prices for ESAs and hypothesis of confidential discount for roxadustat showed that the saving for NHS will be kept if roxadustat’s discount is greater than 60.3%.

Symptom Burden and Altered Mineral Metabolism in Advanced Chronic Kidney Disease: Two Peas in a Pod.

Symptom Burden and Altered Mineral Metabolism in Advanced Chronic Kidney Disease: Two Peas in a Pod.

Recent updates on the influence of iron and magnesium on vascular, renal, and adipose inflammation and possible consequences for hypertension.

The inflammatory status of the kidneys, vasculature, and perivascular adipose tissue (PVAT) has a significant influence on blood pressure and hypertension. Numerous micronutrients play an influential role in hypertension-driving inflammatory processes, and recent reports have provided bases for potential targeted modulation of these micronutrients to reduce hypertension. Iron overload in adipose tissue macrophages and adipocytes engenders an inflammatory environment and may contribute to impaired anticontractile signalling, and thus a treatment such as chelation therapy may hold a key to reducing blood pressure. Similarly, magnesium intake has proven to greatly influence inflammatory signalling and concurrent hypertension in both healthy animals and in a model for chronic kidney disease, demonstrating its potential clinical utility. These findings highlight the importance of further research to determine the efficacy of micronutrient-targeted treatments for the amelioration of hypertension and their potential translation into clinical application.