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Abstract Background Gastrointestinal bleeding (GIB) is a clinical challenge in kidney failure. INSPIRE group assessed if machine learning could determine a hemodialysis (HD) patient’s 180-day GIB hospitalization risk. Methods An eXtreme Gradient Boosting (XGBoost) and logistic regression model were developed using an HD dataset in United States (2017–2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤ 180 days before GIB hospitalization were classified as positive observations; others were negative. Models considered 1,303 exposures/covariates. Performance was measured using unseen testing data. Results Incidence of 180-day GIB hospitalization was 1.18% in HD population (n = 451,579), and 1.12% in testing dataset (n = 38,853). XGBoost showed area under the receiver operating curve (AUROC) = 0.74 (95% confidence interval (CI) 0.72, 0.76) versus logistic regression showed AUROC = 0.68 (95% CI 0.66, 0.71). Sensitivity and specificity were 65.3% (60.9, 69.7) and 68.0% (67.6, 68.5) for XGBoost versus 68.9% (64.7, 73.0) and 57.0% (56.5, 57.5) for logistic regression, respectively. Associations in exposures were consistent for many factors. Both models showed GIB hospitalization risk was associated with older age, disturbances in anemia/iron indices, recent all-cause hospitalizations, and bone mineral metabolism markers. XGBoost showed high importance on outcome prediction for serum 25 hydroxy (25OH) vitamin D levels, while logistic regression showed high importance for parathyroid hormone (PTH) levels. Conclusions Machine learning can be considered for early detection of GIB event risk in HD. XGBoost outperforms logistic regression, yet both appear suitable. External and prospective validation of these models is needed. Association between bone mineral metabolism markers and GIB events was unexpected and warrants investigation. Trial registration This retrospective analysis of real-world data was not a prospective clinical trial and registration is not applicable. Graphical Abstract

In hemodialysis (HD), complement activation, bioincompatibility, and inflammation are intricately intertwined. In the 1970s, as HD became a routine therapy, the observation of complement pathway activation and transient leukopenia by cellulosic dialysis membranes triggered the bioincompatibility debate and its clinical relevance. Extensive deliberations have covered definitions, assessment markers, scope, and long-term clinical consequences of membrane-dependent bioincompatibility reactions. While complement pathways’ interplay with coagulation and inflammation has been delineated, HD’s focus has primarily been on developing more biocompatible membranes using advanced technologies. Recent advances and understanding of the current HD delivery mode (4-hour sessions, thrice weekly) suggest that factors beyond membrane characteristics play a significant role, and a more complex, multifactorial picture of bioincompatibility is emerging. Chronic activation of the complement system and persistent low-grade “uremic inflammation” in chronic kidney disease (CKD) and HD lead to premature inflammaging of the kidney, resembling aging in the general population. Cellular senescence, modulated by complement activation and the uremic milieu, contributes to chronic inflammaging. Additionally, the formation of neutrophil extracellular traps (NETs, process of NETosis) during HD and their biological activity in the interdialytic period can lead to dialysis-induced systemic stress. Thus, complement-inflammation manifestations in HD therapies extend beyond traditional membrane-related bioincompatibility consequences. Recent scientific knowledge is reshaping strategies to mitigate detrimental consequences of bioincompatibility, both technologically and in HD therapy delivery modes, to improve dialysis patient outcomes.

ABSTRACTIn today’s industrialized society food consumption has changed immensely toward heightened red meat intake and use of artificial sweeteners instead of grains and vegetables or sugar, respectively. These dietary changes affect public health in general through an increased incidence of metabolic diseases like diabetes and obesity, with a further elevated risk for cardiorenal complications. Research shows that high red meat intake and artificial sweeteners ingestion can alter the microbial composition and further intestinal wall barrier permeability allowing increased transmission of uremic toxins like p-cresyl sulfate, indoxyl sulfate, trimethylamine n-oxide and phenylacetylglutamine into the blood stream causing an array of pathophysiological effects especially as a strain on the kidneys, since they are responsible for clearing out the toxins. In this review, we address how the burden of the Western diet affects the gut microbiome in altering the microbial composition and increasing the gut permeability for uremic toxins and the detrimental effects thereof on early vascular aging, the kidney per se and the blood-brain barrier, in addition to the potential implications for dietary changes/interventions to preserve the health issues related to chronic diseases in future.

Purpose of symposiumFrom September 6 – 8 2022, the Life/2022 Membrane Symposium was held in Frankfurt, Germany, and transmitted live to a worldwide internet audience. The event was part of the Life/Nephrology Campus initiative, a continuous educational platform for the nephrology community to expand knowledge and share expertise on contemporary topics in chronic kidney disease. We describe recent questions and advances in the field, and we underline challenges in the care of dialysis patients and opportunities for integration of new findings into clinical practice to improve patient outcomes in end stage kidney disease patients.TopicsMost patients with kidney failure are on maintenance hemodialysis (MHD). The scientific program of the symposium was developed around topics about the role, functional determinants, technical aspects, limitations, and clinical implications of membranes presently in use. International experts with clinical or technical expertise as well as scientific recognition within the nephrology community were asked to prepare their presentations based on their own experiences, perceptions, opinions, and sources of information. The symposium devoted a major portion to discussing novel approaches for improving membranes and treatment quality, including updates on innovative concepts that may could potentially transform the landscape of kidney replacement therapy for chronic kidney disease patients in the future.ImplicationsThe intent was to provide insights into current attention points for healthcare professionals new to the field of MHD, and to test a unique forum for continuing medical education integrating physician and patient experiences to promote changes in clinical practice. Furthermore, the symposium premiered a specifically developed mixed reality holographic 3D model to demonstrate recent dialyzer innovation diminishing protein fouling on membrane surfaces. As a continuous online educational platform for scientific exchange, this Life/2022 event provided online learning opportunities with on-demand content, with all symposium lectures freely available on nephrologycampus.com.

Abstract Background The consequences of chronic kidney disease (CKD) can be addressed with a range of pharmacotherapies primarily prescribed by nephrologists. More accurate information regarding future CKD-related pharmacotherapy requirements could guide clinical decisions including follow-up frequency. Methods Following assignment to derivation and validation groups (2,1), variables predicting individually future use of vitamin D receptor agonists (VDRA), phosphate binders, erythropoiesis stimulating agents (ESAs) and iron were identified using logistic regression in a prospective cohort study containing demography, comorbidity, hospitalization, laboratory, and mortality data in patients with CKD stage G4/G5 across six European countries. Discriminative ability was measured using C-statistics, and predicted probability of medication use used to inform follow-up frequency. Results A total of 2196 patients were included in the analysis. During a median follow-up of 735 days 648 initiated hemodialysis and 1548 did not. Combinations of age, diabetes status and iPTH, calcium, hemoglobin and serum albumin levels predicted the use of ESA, iron, phosphate binder or VDRA, with C-statistics of 0.70, 0.64, 0.73 and 0.63 in derivation cohorts respectively. Model performance in validation cohorts were similar. Sixteen percent of patients were predicted to have a likelihood of receiving any of these medications of less than 20%. Conclusions In a multi-country CKD cohort, prediction of ESA and phosphate binder use over a two-year period can be made based on patient characteristics with the potential to reduce frequency of follow-up in individuals with low risk for requiring these medications.

The field of evolutionary health is relatively new, and over the last several decades, has come to signify the interest in the extent of mismatch between factors common in our modern world, and our evolutionary milieu, which is a combination of genetic and environmental interactions that have influenced our development over the course of many thousands, if not hundreds of thousands of years.We have covered a wide variety of topics during our conferences; this includes, brain function, sleep and light, various components of the diet, aging, cardiovascular disease, human brain development, exercise, bone health, obesity, vitamin levels, hormonal regulation, inflammation and cancer, with the emphasis on the degree of mismatch between our hominid ancestors and modern humans today. With this most recent conference, we have added topics such as psychological and physical stress, the gut microbiome and the potential role of biomimetics in environmental stressors.We’d like to thank the Journal of Evolutionary Health for allowing us to publish some of the abstracts from our most recent conference.

IntroductionHypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients.MethodsIn secondary analyses of patients from the Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm3 and >100 Houndsfield Units, respectively) using multivariable logistic regression.ResultsAmong 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance.ConclusionsIn hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population.

Background: Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota profile and uremic toxin plasma levels in HD patients. These are secondary analyses from a previous double-blind, randomized clinical study, with 42 patients divided into two groups: the placebo and propolis group received 400 mg of green propolis extract/day for eight weeks. Indole-3 acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) plasma levels were evaluated by reversed-phase liquid chromatography, and cytokines were investigated using the multiplex assay (Bio-Plex Magpix®). The fecal microbiota composition was analyzed in a subgroup of patients (n = 6) using a commercial kit for fecal DNA extraction. The V4 region of the 16S rRNA gene was then amplified by the polymerase chain reaction (PCR) using short-read sequencing on the Illumina NovaSeq PE250 platform in a subgroup. Forty-one patients completed the study, 20 in the placebo group and 21 in the propolis group. There was a positive correlation between IAA and TNF-α (r = 0.53, p = 0.01), IL-2 (r = 0.66, p = 0.002), and between pCS and IL-7 (r = 0.46, p = 0.04) at the baseline. No significant changes were observed in the values of uremic toxins after the intervention. Despite not being significant, microbial evenness and observed richness increased following the propolis intervention. Counts of the Fusobacteria species showed a positive correlation with IS, while counts of Firmicutes, Lentisphaerae, and Proteobacteria phyla were negatively correlated with IS. Two months of propolis supplementation did not reduce the plasma levels of uremic toxins (IAA, IS, and p-CS) or change the fecal microbiota.

Abstract Background Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF. Methods KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables. Results Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p

Abstract Bear bile-farming is common in East and Southeast Asia and this farming practice often results in irreversible health outcomes for the animals. We studied long-term effects of chronic bacterial and sterile hepatobiliary inflammation in 42 Asiatic black bears (Ursus thibetanus) rescued from Vietnamese bile farms. The bears were examined under anesthesia at least twice as part of essential medical interventions. All bears were diagnosed with chronic low-grade sterile or bacterial hepatobiliary inflammation along with pathologies from other systems. Our main finding was that the chronic low-grade inflammatory environment associated with bile extraction in conjunction with the suboptimal living conditions on the farms promoted and accelerated the development of age-related pathologies such as chronic kidney disease, obese sarcopenia, cardiovascular remodeling, and degenerative joint disease. Through a biomimetic approach, we identified similarities with inflammation related to premature aging in humans and found significant deviations from the healthy ursid phenotype. The pathological parallels with inflammageing and immuno-senescence induced conditions in humans suggest that bile-farmed bears may serve as animal models to investigate pathophysiology and deleterious effects of lifestyle-related diseases.

Background: Both lower and higher estradiol (E2) levels have been associated with increased mortality among women with kidney failure. However, robust data are still lacking. Objective: We investigated the interaction of diabetes and age on linear and nonlinear associations between E2 levels, adverse outcomes, and health-related quality of life (HRQOL) in Canadian women undergoing hemodialysis (HD). Design: Population-based cohort study; data from Canadian Kidney Disease Cohort Study (CKDCS). Setting & patients: A total of 427 women undergoing HD enrolled in the CKDCS. Measurements: Baseline E2 (in pmol/L) and E2 tertiles (95 pmol/L). Methods: Cox-proportional hazards used for all-cause and cardiovascular disease (CVD) mortality. Fine-Gray models used for incident CVD. Mixed models used for Health Utilities Index Mark 3 (HUI3), Kidney Disease Quality of Life Physical Component Scores (KDQOL12-PCS), and Mental Component Scores (KDQOL12-MCS). Results: Over a median follow-up of 3.6 (interquartile range [IQR]: 1.6-7.5) years, 250 (58.6%) participants died; 74 deaths (29.6%) were CV-related. Among 234 participants without prior CV events, 80 (34.2%) had an incident CVD event. There were no significant linear associations between E2 and all-cause mortality, CVD mortality, and incident CVD. However, E2 showed a significant concave association with all-cause mortality, but not with CVD mortality and incident CVD. Among patients aged ≥63 years, higher E2 levels were associated with lower HUI3 scores, mean difference (MD) = –0.062 per 1 – SD pmol/L, 95% confidence interval (CI) = –0.112 to –0.012, but the opposite was observed in younger patients (

Cinnamon, a member of the Lauraceae family, has been widely used as a spice and traditional herbal medicine for centuries and has shown beneficial effects in cardiovascular disease, obesity, and diabetes. However, its effectiveness as a therapeutic intervention for chronic kidney disease (CKD) remains unproven. The bioactive compounds within cinnamon, such as cinnamaldehyde, cinnamic acid, and cinnamate, can mitigate oxidative stress, inflammation, hyperglycemia, gut dysbiosis, and dyslipidemia, which are common complications in patients with CKD. In this narrative review, we assess the mechanisms by which cinnamon may alleviate complications observed in CKD and the possible role of this spice as an additional nutritional strategy for this patient group.

Summary: Sarcopenia is a common and devastating condition in patients with chronic kidney disease (CKD). Here, we provide evidence that the kidney-muscle crosstalk in sarcopenia is mediated by reduced insulin sensitivity and the activation of the muscle-specific isoform of AMP deaminase, AMPD1. By using a high protein-based CKD model of sarcopenia in mice and differentiated human myotubes, we show that urea reduces insulin-dependent glucose and phosphate uptake by the skeletal muscle, thus contributing to the hyperphosphatemia observed in CKD whereas depleting intramuscular phosphate needed to restore energy and inhibit AMPD1. Hyperactivated AMPD1, in turn, aggravates the low energy state in the muscle by removing free adenosine monophosphate (AMP) and producing proinflammatory factors and uric acid which contribute to the progression of kidney disease. Our data provide molecular and metabolic evidence supporting the use of strategies aimed to improve insulin sensitivity and to block AMPD1 to prevent sarcopenia in subjects with CKD.

Circulating cell-free DNA (cfDNA) has diverse applications in oncological, prenatal, toxicological, cardiovascular, and autoimmune diseases, diagnostics, and organ transplantation. In particular, mitochondrial cfDNA (mt-cfDNA) is associated with inflammation and linked to early vascular ageing (EVA) in end-stage kidney failure (ESKF), which could be a noninvasive marker for graft rejection and organ damage. Plasma samples from 44 ESKF patients, of whom half (n = 22) underwent either conservative therapy (non-HD) or hemodialysis (HD) before kidney transplantation (KT). These samples were analyzed at baseline and two years after KT. cfDNA was extracted from plasma and quantified using the fluorometric method. qPCR was used to quantify and differentiate the fractions of mt-cfDNA and nuclear cfDNA (nc-cfDNA). mt-cfDNA levels in KT patients decreased significantly from baseline to two years post-KT (p < 0.0268), while levels of total cfDNA and nc-cfDNA did not differ. Depending on therapy modality (HD vs. non-HD) before KT, total cfDNA levels were higher in HD patients at both baseline (p = 0.0133) and two years post-KT (p = 0.0421), while nc-cfDNA levels were higher in HD only at baseline (p = 0.0079). Males showed a nonsignificant trend of higher cfDNA levels. Patients with assessed vascular fibrosis (p = 0.0068), either alone or in combination with calcification plus fibrosis, showed reduced mt-cfDNA post-KT (p = 0.0195). Changes in mt-cfDNA levels suggests the impact of KT on the inflammatory state of ESKF, as evidenced via its correlation with high sensitivity C-reactive protein after KT. Further studies are warranted to assess if cfDNA could serve as a noninvasive method for monitoring the response to organ transplantation and even for amelioration of EVA status per se.

Abstract Kidney failure and associated uraemia have implications for the cardiovascular system, brain, and blood–brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, and gut-blood barrier (GBB) disruption by trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions and modulation via TMAO were assessed. Serum from chronic kidney disease (CKD) female and male haemodialysis (HD) patients, and controls, were used to measure BDNF and NSE by enzyme-linked immunosorbent assays, and TMAO by mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies from kidney transplant recipients, and controls, were used to measure microvascular expression of tight-junction proteins (claudin-5, occludin, JAM-1), and control microvasculature for TMAO effects. HD patients versus controls, had significantly lower and higher serum levels of BDNF and NSE, respectively. In CKD biopsies versus controls, reduced expression of claudin-5, occludin, and JAM-1 were observed. Incubation with TMAO significantly decreased expression of all tight-junction proteins in the microvasculature. Uraemia affects BBB and GBB resulting in altered levels of circulating NSE, BDNF and TMAO, respectively, and it also reduces expression of tight-junction proteins that confer BBB maintenance. TMAO serves as a potential candidate to alter BBB integrity in CKD.

BackgroundAnthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated.MethodsIn a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST).ResultsChronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92, p = 0.027; Wald test = 4.95, p = 0.026, respectively) and all-cause mortality (Wald test = 5.24, p = 0.022; Wald test = 5.19, p = 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time.ConclusionAbdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients.

Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism.

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

Poor nutritional status and protein-energy wasting are common among maintenance dialysis patients and associated with unfavorable outcomes. Providing foods, meal trays, snack boxes, and/or oral nutritional supplements during hemodialysis can improve nutritional status and might also reduce inflammation, enhance health-related quality of life, boost patient satisfaction, and improve survival. Potential challenges include postprandial hypotension and other hemodynamic instabilities, aspiration risk, gastrointestinal symptoms, hygiene issues, staff burden, reduced solute removal, and increased costs. Differing in-center nutrition policies exist within organizations and countries around the world. Recent studies have demonstrated clinical benefits and highlight the need to work toward clear guidelines. Meals or supplements during hemodialysis may be an effective strategy to improve nutritional status with limited reports of complications in real-world scenarios. Whereas larger multicenter randomized trials are needed, meals and supplements during hemodialysis should be considered as a part of the standard-of-care practice for patients without contraindications.

Given the pathophysiological continuum of chronic kidney disease (CKD), different molecular determinants affecting progression may be associated with distinct disease phases; thus, identification of these players are crucial for guiding therapeutic decisions, ideally in a non-invasive, repeatable setting. Analyzing the urinary peptidome has been proven an efficient method for biomarker determination in CKD, among other diseases. In this work, after applying several selection criteria, urine samples from 317 early (stage 2) and advanced (stage 3b–5) CKD patients were analyzed using capillary electrophoresis coupled to mass spectrometry (CE-MS). The entire two groups were initially compared to highlight the respective pathophysiology between initial and late disease phases. Subsequently, slow and fast progressors were compared within each group in an attempt to distinguish phase-specific disease progression molecules. The early vs. late-stage CKD comparison revealed 929 significantly different peptides, most of which were downregulated and 268 with collagen origins. When comparing slow vs. fast progressors in early stage CKD, 42 peptides were significantly altered, 30 of which were collagen peptide fragments. This association suggests the development of structural changes may be reversible at an early stage. The study confirms previous findings, based on its multivariable-matched progression groups derived from a large initial cohort. However, only four peptide fragments differed between slow vs. fast progressors in late-stage CKD, indicating different pathogenic processes occur in fast and slow progressors in different stages of CKD. The defined peptides associated with CKD progression at early stage might potentially constitute a non-invasive approach to improve patient management by guiding (personalized) intervention.

Residual kidney function for patients with chronic kidney disease (CKD) is associated with better quality of life and outcome; thus, strategies should be implemented to preserve kidney function. Among the multiple causes that promote kidney damage, gut dysbiosis due to increased uremic toxin production and endotoxemia need attention. Several strategies have been proposed to modulate the gut microbiota in these patients, and diet has gained increasing attention in recent years since it is the primary driver of gut dysbiosis. In addition, medications and faecal transplantation may be valid strategies. Modifying gut microbiota composition may mitigate chronic kidney damage and preserve residual kidney function. Although various studies have shown the influential role of diet in modulating gut microbiota composition, the effects of this modulation on residual kidney function remain limited. This review discusses the role of gut microbiota metabolism on residual kidney function and vice versa and how we could preserve the residual kidney function by modulating the gut microbiota balance.

A new network of over 72 organizations from 12 countries was activated during a convening at ARTIS in Amsterdam on 26–27 September 2022. Representatives are aligned with the transdisciplinary field and social movement of Planetary Health, which analyzes and addresses the impacts of human disruptions to natural systems on human health and all life on Earth. The new European Planetary Health Hub consists of organizations from various sectors, including universities, healthcare, youth, business, and civil society. The Convening, co-organized by the Planetary Health Alliance (PHA), the European Environment and Sustainable Development Advisory Councils Network (EEAC), and Natura Artis Magistra (ARTIS), aimed to develop Planetary Health Working Groups for Education, Policy Engagement, Research, and Movement Building. The Convening resulted in an outline for each of the Working Group’s aims, visions, missions, priorities, and activities, and set the framework for sustaining their activities in the future through the establishment of the European Planetary Health Hub Secretariat in the Netherlands. The Hub members shared lessons learned, built relationships, and developed artwork-inspired perspectives on Planetary Health. In conclusion, the Convening led to the establishment of a strong European foundation to contribute to the transformations needed for sustainable, just, and equitable societies that flourish within the limits of our ecosystems.

Cardiovascular disease is the main cause of early death in the settings of chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing. Cardiovascular events can be caused by an imbalance between promoters and inhibitors of mineralization, which leads to vascular calcification. This process is akin to skeletal mineralization, which is carefully regulated and in which isozymes of alkaline phosphatase (ALP) have a crucial role. Four genes encode ALP isozymes in humans. Intestinal, placental and germ cell ALPs are tissue-specific, whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several tissues, including bone, liver and kidney. TNALP has a pivotal role in bone calcification. Experimental overexpression of TNALP in the vasculature is sufficient to induce vascular calcification, cardiac hypertrophy and premature death, mimicking the cardiovascular phenotype often found in CKD and T2DM. Intestinal ALP contributes to the gut mucosal defence and intestinal and liver ALPs might contribute to the acute inflammatory response to endogenous or pathogenic stimuli. Here we review novel mechanisms that link ALP to vascular calcification, inflammation, and endothelial dysfunction in kidney and cardiovascular diseases. We also discuss new drugs that target ALP, which have the potential to improve cardiovascular outcomes without inhibiting skeletal mineralization.

Chronic kidney disease (CKD) is a prevalent disease among felids; yet its origin is still poorly understood, and the disease often remains asymptomatic for years, underscoring the need for early diagnosis. This study aimed to investigate the diagnostic value of urinalysis in accurately staging CKD, particularly as routine health checks in large felids often overlook its significance. In this research, ultrasound-guided cystocentesis (UGC) was performed on 50 captive nondomestic felids during routine veterinary health checks under general anesthesia. Urinalysis included microscopic examination of the sediment, measurement of urine specific gravity (USG) and protein to creatinine ratio (UPC). Additional serum kidney markers, such as creatinine and symmetric dimethylarginine, were compared with USG and UPC to assess their diagnostic value as urinary biomarkers. The results demonstrated proteinuria (UPC > 0.4) or borderline proteinuria (UPC 0.2–0.4) in 49% of the animals. Among these cases, 62% were of renal origin, and 38% were postrenal causes. USG was significantly higher in felids with borderline proteinuria compared to those with proteinuria. A moderate, but significant negative correlation between serum parameters and USG was observed, emphasizing the importance of assessing both diagnostic parameters during kidney evaluations. Additionally, felids with CKD have an increased risk of urinary tract infections, necessitating microscopic urinalysis and bacterial culture analysis. Abnormalities, including hematuria, pyuria, crystalluria, and bacteriuria, were found in approximately 38% of cases through microscopical examination of urine. No complications associated with UGC were observed and abnormal findings were detected in 60% of the cases. Based on these results, the authors recommend the inclusion of UGC and urinalysis as standard diagnostic tools in general health checks for nondomestic felids. This approach provides valuable insights into the early detection and staging of CKD, supporting early intervention and supportive medical care to prolong renal health in these animals. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) afflicts 15% of adults in the United States, of whom 25% have a family history. Genetic testing is supportive in identifying and possibly confirming diagnoses of CKD, thereby guiding care. Advances in the clinical genetic evaluation include next-generation sequencing with targeted gene panels, whole exome sequencing, and whole genome sequencing. These platforms provide DNA sequence reads with excellent coverage throughout the genome and have identified novel genetic causes of CKD. New pathologic genetic variants identified in previously unrecognized biological pathways have elucidated disease mechanisms underlying CKD etiologies, potentially establishing prognosis and guiding treatment selection. Molecular diagnoses using genetic sequencing can detect rare, potentially treatable mutations, avoid misdiagnoses, guide selection of optimal therapy, and decrease the risk of unnecessary and potentially harmful interventions. Genetic testing has been widely adopted in pediatric nephrology; however, it is less frequently used to date in adult nephrology. Extension of clinical genetic approaches to adult patients may achieve similar benefits in diagnostic refinement and treatment selection. This review aimed to identify clinical CKD phenotypes that may benefit the most from genetic testing, outline the commonly available platforms, and provide examples of successful deployment of these approaches in CKD.

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.