Chronic kidney disease (CKD) and cardiovascular disease (CVD) have multiple bidirectional mechanisms, and anaemia is one of the critical factors that are associated with the progression of the two disorders [referred to as cardiorenal anaemia syndrome (CRAS)]. Several lines of evidence indicate that CRAS confers a worse prognosis, suggesting the need to clarify the underlying pathophysiology. Among the micronutrients (trace elements) that are essential to humans, inadequate iron status has previously been implicated in the pathogenesis of CRAS; however, the roles of other trace elements remain unclear. Selenium critically regulates the function of selenoproteins, in which selenocysteine is present at the active centres. The human genome encodes 25 selenoproteins, and accumulating data indicate that they regulate diverse physiological processes, including cellular redox homeostasis, calcium flux, thyroid hormone activity and haematopoiesis, all of which directly or indirectly influence cardiac function. The essential role of selenium in human health is underscored by the fact that its deficiency results in multiple disorders, among which are cardiomyopathy and abnormal erythrocyte morphology. Studies have shown that selenium deficiency is not uncommon in CKD patients with poor nutritional status, suggesting that it may be an under-recognized cause of anaemia and cardiovascular disorders in these patients. In this review, we discuss the role of selenium in the pathophysiology of CKD, particularly in the context of the interconnection among CKD, cardiac dysfunction and anaemia. Given that selenium deficiency is associated with treatment-resistant anaemia and an increased risk of CVD, its role as a key modulator of CRAS merits future investigation.

Chronic kidney disease (CKD) poses an increasing challenge to the middle-aged and elderly population. Wenshenyang decoction (WSY), an herbal formula from China, has been shown to have a considerable effect on the recovery of the renal function in a real-world study. However, no randomized, double-blind, placebo-controlled, multicenter clinical trial to evaluate the efficacy and safety yet.

This study aimed to investigate the efficacy, advantages, limitations, and safety, and provide insights into methods and strategies for utilizing WSY in CKD management.

Participants were recruited from six tertiary hospitals in Beijing, China. Eligible participants were randomly assigned to receive either WSY and conventional Western medicine or placebo and conventional Western medicine in a 1:1 ratio. The treatment and follow-up cycles each lasted 90 days, with a total of six follow-up visits. The primary outcome measures were the change in 24-hour urine protein excretion (24h UPRO) and serum creatinine (SCR) from baseline at Visit 3 (90 days after the treatment) and Visit 5 (90 days after the follow-up). The secondary outcome measures were the improvement in symptoms and other renal function indicators. Additionally, we explored the correlation between the effect of WSY treatment and CKD type and stage through subgroup analysis. Finally, the safety of this decoction was assessed.

In total, 257 participants were diagnosed with CKD characterized by kidney Yang deficiency. Of these patients, 240 underwent randomization, and 203 were included in the subsequent analysis. After 180 days of treatment and follow-up, there was a significant decrease in the primary outcome 24h UPRO (a 43.19% improvement at Visit 3, 95% CI: 27.68%, 58.71%; a 51.28% improvement at Visit 5, 95% CI: 31.40%, 71.16%), and SCR (a 16.34% improvement at Visit 3, 95% CI: 11.28%, 21.40%; a 20.52% improvement at Visit 5, 95% CI: 14.05%, 26.99%). Compared to the control group, the difference was statistically significant (p < 0.05). Additionally, the secondary outcome of symptom score showed that 79.21% of the patients felt "completely improved" and "greatly improved"; which was much higher than placebo (p < 0.05). Subgroup analysis showed that WSY was more effective for diabetic kidney disease (DKD) and stage 3 of CKD. No severe adverse events occurred during the period.

These results indicate that WSY could improve the renal function and alleviate the kidney Yang deficiency symptoms in patients with CKD without adverse effects. This study provided evidence-based medicine in the treatment of CKD with compound prescriptions of traditional Chinese medicine (TCM) and contributed to promoting the use of phytomedicine.

Renal aging is a physiological process characterized by structural and functional changes in the kidneys. The presence of disorders or pathologies can exacerbate these age-related changes, potentially leading to organ dysfunction. Chronic kidney disease (CKD), a significant global public health issue, is particularly prevalent in the elderly and is often associated with the age-related decline in kidney function. Anemia is one of the most frequent complications of CKD and is also highly prevalent in the elderly. Mild anemia, often multifactorial, is the most common presentation. Understanding the mechanisms driving anemia in this population is crucial to ensure appropriate treatment. The primary etiologies include nutritional deficiency, anemia of unknown cause, and anemia of chronic diseases, including CKD. This review provides an in-depth exploration of the complex pathophysiological mechanisms underlying anemia in elderly patients with CKD.

Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, sharing significant overlap in prevalence and pathophysiological mechanisms. This coexistence, termed cardiorenal syndrome (CRS), often leads to anemia, which exacerbates both HF and CKD, thereby increasing morbidity and death. Managing anemia in CRS is complex due to conflicting guidelines and the multifactorial nature of the condition. Anemia in CRS is influenced by factors such as inadequate erythropoietin production, iron deficiency, reduced red blood cell life span, and chronic inflammation, which inhibit iron absorption and mobilization. This interplay of mechanisms worsens anemia, further aggravating HF and CKD. Anemia significantly impacts the prognosis of both HF and CKD, and recent trials have shown that hemoglobin increases, particularly with sodium-glucose cotransporter 2 inhibitors, can improve outcomes in patients with HF and CKD. Iron deficiency is also prevalent in both patients with HF and patients with CKD and is associated with poorer exercise capacity and a higher mortality rate. Guidelines for diagnosing and treating iron deficiency differ between HF and CKD. Furthermore, treatment of anemia in CRS is controversial: While sodium-glucose cotransporter 2 inhibitors and intravenous iron has shown consistent benefits in patients with CRS, normalization of hemoglobin with erythropoiesis-stimulating agents improves symptoms and quality of life but have not consistently demonstrated cardiovascular benefits. There are no definitive guidelines for anemia management in CRS. Treatment should address HF, CKD, and anemia concurrently. A proposed algorithm includes correcting iron deficiency, initiating sodium-glucose cotransporter 2 inhibitors, and considering erythropoiesis-stimulating agents if hemoglobin remains <10 g/dL. Further research is needed to optimize anemia management strategies in patients with CRS.

Paediatric patients undergoing haemodialysis typically require intravenous (IV) iron therapy to replenish iron stores. Upon establishing our home haemodialysis service, the need for an efficient IV iron administration method prompted exploration beyond the conventional use of iron sucrose, which is associated with anaphylaxis and requires frequent infusions. Ferric carboxymaltose has a favourable safety profile and corrects iron deficiency with less frequent infusions. We aimed to establish if ferric carboxymaltose was a viable alternative in this patient group.

This single-centre, uncontrolled retrospective cohort study assessed the effectiveness of ferric carboxymaltose in maintaining laboratory parameters (haemoglobin level, transferrin saturation and reticulocyte haemoglobin content) within target range in our home haemodialysis population. Secondly, we conducted a comparative analysis to establish maintenance efficacy of ferric carboxymaltose, versus iron sucrose over a 12-month period. Finally, we performed a cost-effectiveness analysis of IV iron therapy, considering cost per dose and per month of treatment.

Following ferric carboxymaltose infusion, we observed significant increases in haemoglobin level, transferrin saturation and reticulocyte haemoglobin content, which was maintained at 3-month post-infusion. Ferric carboxymaltose demonstrated comparable efficacy to iron sucrose in maintaining laboratory parameters. Strikingly, ferric carboxymaltose treatment was associated with significantly decreased number of infusions per month (~ tenfold) and a significant cost-saving (~ fivefold).

This study underscores the clinical efficacy and economic benefits of ferric carboxymaltose as a viable treatment for iron deficiency anaemia in paediatric patients who are haemodialysis-dependent and highlights the potential for significant improvements in healthcare delivery, in terms of reducing frequency of hospital visits for this patient population.

Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness. A novel interleukin-6 monoclonal antibody, ziltivekimab, has been evaluated for managing anemia in chronic kidney disease patients in pilot clinical trials with promising outcomes, including an improvement in hemoglobin levels and reduction of inflammatory parameters. These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. Furthermore, potentially beneficial effects on serum lipid profile have been reported, leading to the hypothesis of a favorable impact of the drug on atherosclerotic complications. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way.

Anemia is common among HIV/AIDS patients, impacting prognosis. Particulate matter (PM) exposure is an understudied, potentially modifiable risk factor in this group.

We gathered 36,266 hemoglobin (Hb) measurements from 6808 HIV/AIDS patients from the HIV/AIDS Comprehensive Response Information Management System from 1 January 2004 to 31 December 2021. We evaluated the relationship between Hb levels and short-term PM exposure using linear mixed-effects models. We used logistic regression to estimate the association of long-term PM exposure with baseline anemia prevalence and time-varying Cox models to estimate the association of long-term PM exposure with follow-up incidence of anemia. Mediation analysis explored the role of chronic kidney disease (CKD) in the association between PM exposure and anemia.

For every 5 µg/m³ increase in 28-day average PM 1 , Hb levels decreased by 0.43 g/l. For a 10 µg/m³ increase in PM 2.5 , Hb decreased by 0.55 g/l; for the same increase in PM 10, Hb decreased by 0.35 g/l. A 5 µg/m³ increase in 1-year average PM 1 corresponded to a 7% higher prevalence of anemia at baseline, a 10 µg/m³ increase in PM 2.5 to 8% higher prevalence, and a 10 µg/m³ increase in PM 10 to 6% higher prevalence. These rises in average PM concentrations during follow-up were associated with increased incident anemia by 54% (PM 1 ), 72% (PM 2.5 ), and 51% (PM 10 ). CKD partially mediated the positive associations between PM exposure and the incidence of anemia.

PM exposure was associated with lower Hb levels and higher incidence of anemia in HIV/AIDS patients and CKD with mediating estimated effects in PM-induced anemia.

Chronic kidney disease (CKD) and, in particular, chronic haemodialysis (HD) patients have a high risk of developing sleep disorders and executive dysfunction. Sleep disorders have a prevalence of 75 % in the haemodialysed population and several causes are behind their occurrence: sympatho-vagal imbalances, low melatonin production, vitamin D deficiency, altered cerebral haemodynamics and haemodialysis-induced vascular stress. Executive dysfunction affects about 55 % of haemodialysis patients. The causes can be ascribed to dysfunctions of the frontal lobes. HD patients show frontal brain atrophy and reduced brain activity and connectivity of several frontal and prefrontal areas. Sleep quality also has a significant impact on executive functions; inefficient and fragmented sleep reduces the efficiency of executive functions and increases the risk of dementia. Sleep deprivation also alters the connectivity and structure of several frontal areas. Thus, sleep and executive functions seem to be closely linked. Multidisciplinary care of patients with CKD and in HD appears essential to structure preventive interventions, pharmacological and non-pharmacological treatments that can improve sleep quality, preserve the integrity of executive functions and improve their quality of life.

Anaemia is a frequent and serious complication in chronic kidney disease (CKD), affecting both non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients. While erythropoietin (EPO) deficiency is the primary cause, iron deficiency (ID) also plays a crucial role. ID in CKD can be classified as either absolute, resulting from blood loss, or functional, driven by inflammation and elevated hepcidin levels, which trap iron in macrophages and hepatocytes, preventing its use in erythropoiesis. Elevated hepcidin also reduces dietary iron absorption in the gut, making oral iron supplements ineffective, particularly in advanced CKD. This review summarises the available intravenous (IV) iron formulations, discusses diagnostic definitions and treatment thresholds for ID in NDD and DD CKD, and explores potential future therapeutic directions.

A core feature of universal health coverage is equitable access to affordable care not exposing people to financial hardship. This study aims to provide a global overview on availability and access to medications and health technologies for delivery of optimal kidney care. An international survey of stakeholders (clinicians, policymakers, and patient advocates) from countries affiliated to the International Society of Nephrology was conducted from July to September 2022 on availability of tools and services for all aspects of kidney care and access to essential medications. Of 167 participating countries (97.4% of the global population), there were significant disparities in kidney care funding and service availability. Only 5 (n = 1) and 10% (n = 4) of countries in Latin America and Africa, respectively, publicly funded non-dialysis CKD care free at the point of delivery, compared to73% (n = 16) in Western Europe. Public funding (and free at point of delivery) for medications for dialysis and kidney transplantation was available in only 24% (n = 39) and 30% (n = 50) of countries worldwide, with the proportion increasing in line with country income levels. There was reduced capacity for the management of CKD mineral bone disease in low-income countries (LICs) - serum parathyroid hormone was available in only 26% (n = 5) of LICs and the ability to administer non-calcium-based phosphate binders and cinacalcet was also very limited in LICs [16% (n = 3) and 5% (n = 1), respectively]. Nutritional services like oral supplements were accessible in 32% (n = 6) of LICs versus 97% (n = 61) of high-income countries. This study highlights significant gaps in the global methods of funding and availability of medications, capacity for kidney disease monitoring, and capacity to treat complications of kidney disease to improve outcomes. Achieving universal and equitable access to essential medications and health technologies for kidney care is vital to tackle the rapidly growing global burden of kidney disease.

Maintaining iron homeostasis is necessary for kidney functioning. There is more and more research indicating that kidney disease is often caused by iron imbalance. Over the past decade, ferroptosis' role in mediating the development and progression of renal disorders, such as acute kidney injury (renal ischemia-reperfusion injury, drug-induced acute kidney injury, severe acute pancreatitis induced acute kidney injury and sepsis-associated acute kidney injury), chronic kidney disease (diabetic nephropathy, renal fibrosis, autosomal dominant polycystic kidney disease) and renal cell carcinoma, has come into focus. Thus, knowing kidney iron metabolism and ferroptosis regulation may enhance disease therapy. In this review, we discuss the metabolic and molecular mechanisms of iron signaling and ferroptosis in kidney disease. We also explore the possible targets of ferroptosis in the therapy of renal illness, as well as their existing limitations and future strategies.

HIF-2α, encoded by EPAS1, plays a dominant role in regulating erythropoietin (EPO) production, maintaining the dynamic balance of erythropoiesis. Gain-of-function mutations in EPAS1 cause erythrocytosis. However, anaemia caused by EPAS1 loss-of-function mutations has been confined to only one case report, and the underlying mechanism remains unclear. Herein, the reanalysis of high-throughput sequencing data from 311 patients with anaemia identified three monoallelic EPAS1 variants from three unrelated families in a paediatric anaemia cohort. The probands showed highly consistent clinical phenotypes with normocytic and normochromic anaemia, reticulocytopenia and relative deficiency of serum EPO, characterised as congenital hypoplastic anaemia. In vitro studies suggested that defects in steady-state protein abundance, nuclear localisation and binding with co-activator in EPAS1 variants lead to impaired EPO transcriptional activation. Therefore, loss-of-function mutations in EPAS1 can cause erythroid hypoplasia in an EPO-dependent manner. This study identified a new causative gene for congenital hypoplastic anaemia and clarified the molecular aetiology of loss-of-function EPAS1 mutations.

Anemia is common in patients with chronic kidney disease and type 2 diabetes. Finerenone improved heart and kidney outcomes in patients with chronic kidney disease and type 2 diabetes in FIDELITY.

This post hoc analysis investigated the efficacy and safety of finerenone vs placebo by baseline anemia status.

Anemia was defined as serum hemoglobin levels <13 g/dL (male) or <12 g/dL (female) or treatment with an erythropoiesis-stimulating agent at baseline. Outcomes included cardiovascular (CV) and kidney composites, hospitalization for heart failure, and all-cause mortality. Safety was assessed through treatment-emergent adverse events.

Of 12,971 patients, 33% had anemia at baseline. Finerenone reduced the risk of the CV composite outcome to a greater extent in patients with vs without anemia (HR: 0.75 [95% CI: 0.65-0.88] vs HR: 0.93 [95% CI: 0.82-1.05]; P for interaction = 0.03). Finerenone reduced the risk of the kidney composite outcome vs placebo, with no heterogeneity between patients with vs without anemia (HR: 0.79 [95% CI: 0.65-0.95] and HR: 0.74 [95% CI: 0.60-0.91]; P for interaction = 0.77). The risk of hospitalization for heart failure and all-cause mortality was lower with finerenone vs placebo, irrespective of anemia status. Patients with anemia experienced higher incidence of treatment-emergent hyperkalemia vs those without.

Finerenone demonstrated CV and kidney benefit in patients with and without anemia. The benefit of finerenone on CV outcomes was greater in patients with vs without anemia at baseline. Anemia is likely a marker for higher-risk patients who are more susceptible to the benefits of finerenone. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease [FIGARO-DKD], NCT02545049).

Chronic kidney disease (CKD) is defined by persistent abnormalities of kidney function or structure that have consequences for the health. A progressive decline of excretory kidney function has effects on body homeostasis. CKD is tightly associated with accelerated cardiovascular disease and severe infections, and with premature death. Kidney failure without access to kidney replacement therapy is fatal - a reality in many regions of the world. CKD can be the consequence of a single cause, but CKD in adults frequently relates rather to sequential injuries accumulating over the life course or to the presence of concomitant risk factors. The shared pathomechanism of CKD progression is the irreversible loss of kidney cells or nephrons together with haemodynamic and metabolic overload of the remaining nephrons, leading to further loss of kidney cells or nephrons. The management of patients with CKD focuses on early detection and on controlling all modifiable risk factors. This approach includes reducing the overload of the remaining nephrons with inhibitors of the renin-angiotensin system and the sodium-glucose transporter 2, as well as disease-specific drug interventions, if available. Hypertension, anaemia, metabolic acidosis and secondary hyperparathyroidism contribute to cardiovascular morbidity and reduced quality of life, and require diagnosis and treatment.

Renal anemia stems mainly from chronic inflammation with elevated hepcidin levels, iron deficiency, and reduced red blood cell lifespan. Inadequate erythropoietin (EPO) production, worsened kidney function, leads to symptoms such as low energy, fatigue, and impaired physical function, significantly affecting patients' quality of life. We conducted a comprehensive search across electronic databases including PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Airiti library, and Wanfang, to compile recent clinical trials and pilot studies on conventional and complementary alternative medicine approaches for renal anemia. This discussion focuses on the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) axis theory, from lab research to clinical applications. It explores non-extracorporeal treatments for renal anemia, including pharmaceutical interventions, dietary strategies, and complementary and alternative medicine (CAM). The article details the effects of Roxadustat, Ferumoxytol, and Epodion. Clinical studies show that modulating the gut microbiome can reduce inflammation and improve renal anemia. Clinical trials suggest that CAM therapy can improve renal anemia through mechanisms such as enhanced iron metabolism, anti-inflammatory effects, reduced hepcidin levels, and increased EPO and HIF expressions. By synthesizing this information, the review aims to furnish valuable insights and treatment recommendations aimed at ameliorating renal anemia in individuals grappling with chronic kidney disease.

Erythroferrone (ERFE) has emerged as a potential biomarker for the erythropoiesis response following recombinant human erythropoietin (rHuEPO) treatment. While the association between ERFE and hemoglobin (HGB) response to rHuEPO is well-established in nonanemic conditions, such correlation and ERFE kinetics in anemic states remain unclear. We employed two rat models of anemia, chronic kidney disease (CKD) anemia and chemotherapy-induced anemia (CIA), to determine ERFE kinetics and its correlation with HGB responses after rHuEPO administration. The key factors influencing ERFE kinetics were characterized using a PK/PD modeling approach and supported by experimentation. Following rHuEPO injection, ERFE induction was diminished in anemic rats compared with that of healthy rats, primarily attributed to the reduced precursor cell mass and impaired rHuEPO responsiveness. The early increase in ERFE at 4 h post administration allows for the prompt prediction of HGB response and rHuEPO hyporesponsiveness in anemic rats. Consequently, the ERFE-based dose adjustment resulted in a rHuEPO-sparing effect in CKD rats. This strategy is expected to be translatable to anemic patients, potentially reducing rHuEPO doses and mitigating HGB overshooting.

Iron overload is a well-recognized complication in patients suffering from beta-thalassemia major (BTM) and end-stage renal disease (ESRD), recently known as kidney failure (KF), particularly in those who receive frequent blood transfusions or long-term iron supplementation. The mechanisms leading to iron overload differ slightly between these two conditions, but the management principles share considerable overlap. Lessons learned from monitoring and managing iron overload in patients with BTM can provide valuable insights into managing iron overload in patients with KF. This narrative review explores the parallels between these two conditions concerning iron overload, emphasizing the importance of early detection, personalized therapy, multidisciplinary care, patient education, and preventive strategies.

The objective was to review the safety and efficacy of daprodustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) in the treatment of anemia of chronic kidney disease (CKD).

A literature search was conducted in MEDLINE, EMBASE, and ClinicalTrials.gov using the keywords "daprodustat," "GSK1278863," and "hypoxia-inducible factor-prolyl hydroxylase inhibitors" from January 2010 through November 2023.

Literature was included if it evaluated pharmacology, pharmacokinetics, efficacy, and/or safety of daprodustat in human subjects and was reported in English. The manufacturer's product monograph was also utilized.

Daprodustat significantly increased hemoglobin levels in CKD patients on dialysis (difference 0.18 g/dL) and not on dialysis (difference 0.08 g/dL) over 52-week treatment periods compared with erythropoiesis stimulating agents (ESA) in Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat (ASCEND)-D and ASCEND-ND, respectively. First occurrence of major adverse cardiovascular events (MACEs) was similar between daprodustat and ESAs in both trials.

Daprodustat can be used in patients with CKD on dialysis and already receiving an ESA for at least 6 weeks to further increase serum hemoglobin levels without increasing the risk of MACE. Adverse effects of daprodustat that may occur more than ESAs include headache, emesis, and thrombosis.

Daprodustat is a novel oral, non-iron therapy for treatment of anemia of CKD. It was Food and Drug Administration approved in 2023 in patients already receiving dialysis for at least 4 months but not in non-dialysis patients. Long-term data for safety and additional benefits are pending.

» Anemia is a common comorbidity in orthopaedic trauma patients with important clinical consequences, significantly negatively affecting a patient's course following orthopaedic trauma.» Anemia remains relatively understudied in the orthopaedic trauma population with a large amount of current literature focused solely on geriatric hip fracture patients.» Greater investigation into alternatives to blood transfusions such as iron therapy or cell salvaging for treatment of anemia in the orthopaedic trauma population is needed.

Anaemia is a prevalent complication in patients with end-stage kidney disease (ESKD) undergoing haemodialysis. This study evaluates the accuracy of the Alio SmartPatch™, a non-invasive remote monitoring device, in measuring haemoglobin (Hb) and haematocrit (Hct) levels in haemodialysis patients by comparing its results with standard blood-based laboratory methods. The results from 116 patients across multiple sites in the USA and the Kingdom of Jordan show that SmartPatch measurements align closely with standard blood-based laboratory methods, meeting clinically acceptable limits of agreement. The current standard methods of Hb and Hct measurements are invasive and require visits to clinical sites, whereas the FDA-cleared SmartPatch offers non-invasive measurement of these parameters up to 240 times per month, thereby enhancing personalized care and patient engagement. This study demonstrates the potential of remote monitoring technologies, such as the SmartPatch, to improve the management of ESKD-associated anaemia. Further research is warranted to evaluate the device's long-term outcomes and its impact across diverse patient populations.

Chronic kidney disease (CKD) represents a significant global health challenge, characterized by kidney damage and decreased function. Its prevalence has steadily increased, necessitating a comprehensive understanding of its epidemiology, risk factors, and management strategies. While traditional prognostic markers such as estimated glomerular filtration rate (eGFR) and albuminuria provide valuable insights, they may not fully capture the complexity of CKD progression and associated cardiovascular (CV) risks.This paper reviews the current state of renal and CV risk prediction in CKD, highlighting the limitations of traditional models and the potential for integrating artificial intelligence (AI) techniques. AI, particularly machine learning (ML) and deep learning (DL), offers a promising avenue for enhancing risk prediction by analyzing vast and diverse patient data, including genetic markers, biomarkers, and imaging. By identifying intricate patterns and relationships within datasets, AI algorithms can generate more comprehensive risk profiles, enabling personalized and nuanced risk assessments.Despite its potential, the integration of AI into clinical practice faces challenges such as the opacity of some algorithms and concerns regarding data quality, privacy, and bias. Efforts towards explainable AI (XAI) and rigorous data governance are essential to ensure transparency, interpretability, and trustworthiness in AI-driven predictions.

Aims/Background The present study aimed to assess the capability of biomarkers, including inflammatory indicators, anaemic markers, lipid markers, and renal function indices, to differentiate between different stages of chronic kidney disease (CKD). Expected to provide a new strategy for monitoring the development of CKD and stratified treatment management, providing valuable insights for future biomarker studies to explore early detection of CKD. Methods The changes in inflammatory markers (interferon gamma [IFN-γ], interleukin [IL]-17A, IL-10, IL-6, IL-4, IL-2, IL-1 and white blood cells [WBC]), lipid markers (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], and triglyceride [TG]), indicators of kidney injury (serum creatinine [Scr] and blood urea nitrogen [BUN]) in 451 patients with different stages of CKD were examined. Furthermore, these markers were compared between 299 anemic patients and 53 non-anemic patients. Univariate and multivariate regression analyses were employed to analyze the association between these biomarkers and estimated glomerular filtration rate (eGFR). To identify risk factors associated with the development of CKD, we utilized principal component analysis to evaluate their utility as potential diagnostic and prognostic markers for the disease. Results Significant differences were found in IL-6, BUN, and hemoglobin (Hb) levels across CKD stages 2 to 5. Anaemic individuals had elevated levels of IL-6, Scr, and BUN compared to non-anaemic individuals. In addition, the multivariate linear regression analysis revealed that IL-1 (p = 0.022), IL-6 (p = 0.022), Hb (p < 0.001), and BUN (p < 0.001) were statistically significant predictors of eGFR. Furthermore, it was discovered that the blood levels of IL-6 (p = 0.012), BUN (p < 0.001), and Hb (p < 0.001) were risk factors associated with the stages of CKD. Conclusion Serum levels of IL-6, BUN and Hb have been associated with the progression of CKD. Using a combination of serum biomarkers is a potential strategy for tracking the development of CKD, facilitating stratified management and early intervention.

Anemia and chronic kidney disease (CKD), which worsen bidirectionally, are associated with mortality in older adults. This study aimed to examine the association between CKD and the type of anemia and its impact on mortality in the general population. Data from a nationwide database of 203,280 individuals who participated in the annual "Specific Health Check and Guidance in Japan" evaluation between 2008 and 2011 were used. Over a follow-up period of 4 years, 2,819 all-cause, 1,595 cancer-related, 523 cardiovascular, and 128 infectious disease deaths were recorded. Macrocytic anemia was detected in 2.3% of participants. The prevalence of normocytic and macrocytic anemia increased with advancing CKD stage. Multivariate Cox proportional hazards regression analysis revealed significant associations between macrocytic anemia and the all-cause, cancer, and cardiovascular mortality rates. Including the anemia type improved the prediction accuracy for all-cause deaths. The participants were divided into eight groups based on the anemia type and CKD. Macrocytic anemia of CKD had the highest hazard ratio for all-cause mortality in the general population. A correlation was observed between macrocytic anemia and CKD. Macrocytic anemia predicted mortality in the general population, suggesting that it could serve as an early indicator of premature death in high-risk individuals.

Background: Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have been developed as a treatment for renal anemia. However, their therapeutic impact on patients with concomitant heart failure remains uncertain. We investigated the impact of HIF-PH inhibitors on improving renal anemia and associated clinical outcomes in patients with heart failure. Methods: Patients with both heart failure and renal anemia who received HIF-PH inhibitors were retrospectively analyzed over a six-month follow-up period. Hemoglobin levels and other clinical parameters were compared between the six-month pre-treatment period without HIF-PH inhibitors and the six-month treatment period with HIF-PH inhibitors. Results: A total of 69 patients (median age 82 years, 27 male) were included. Baseline hemoglobin was 9.2 (8.8, 10.3) g/dL, baseline plasma B-type natriuretic peptide level was 264 (156, 372) pg/mL, and baseline estimated glomerular filtration rate was 29.1 (19.0, 35.1) mL/min/1.73 m2. Hemoglobin levels declined during the pre-treatment period from 10.5 (9.4, 11.5) g/dL to 9.2 (8.8, 10.3) g/dL (p < 0.001) but subsequently increased to 10.9 (10.1, 12.0) g/dL following six months of HIF-PH inhibitor treatment (p < 0.001). This increase in hemoglobin was accompanied by a reduction in plasma BNP levels, improved renal function, and reduced systemic inflammation (p < 0.05 for all). Conclusions: HIF-PH inhibitors demonstrated efficacy in this cohort of patients with heart failure, with associated improvements in heart failure severity, renal function, and systemic inflammation.

In recent years, ectopic lymphoid tissue (ELT) has been increasingly confirmed as a new biomarker for kidney injury or inflammation. However, there is insufficient research on the relationship between ELT grading and the progression of idiopathic membranous nephropathy (IMN).

A total of 147 patients with biopsy-proven IMN in our institution from March 2020 to June 2022 were classified into five grades based on the different distribution of lymphocyte subsets in renal tissue (G0: no B cells or T cells, G1: scattered B and T cells, G2: clustered B and T cells, G3: an aggregation region of B and T cells without a central network, G4: highly organized and formed zones of B and T cells with a central network of follicular dendritic cells and scattered macrophages), and were further divided into low-grade group (G0+G1), intermediate-grade group (G2) and high-grade group (G3+G4). The clinicopathological data, induction treatment response and prognosis among the three groups were analyzed and compared retrospectively.

As the grading of ectopic lymphoid tissues increased, patients were older, with a higher prevalence of hypertension, a higher 24-h urinary protein level, lower baseline hemoglobin and estimated glomerular filtration rate (eGFR) levels, and more severe renal pathological damage. Logistic regression analysis showed that after 6 months of induction treatment, patients in the high-grade group were more likely to be in non-remission than those in the low-grade group (odds ratios [ORs] of the three adjusted models were 4.310, 4.239, and 5.088, respectively, P-values were 0.005, 0.006, and 0.001, respectively). Kaplan-Meier survival analysis indicated that patients in the intermediate- and high-grade groups had significantly lower renal cumulative survival rate than those in the low-grade group (P = 0.025). Univariate Cox analysis showed that the risk of adverse renal outcome was 3.662 times higher in the intermediate- and high-grade groups than in the low-grade group (95% confidence interval [CI] [1.078-12.435]; P = 0.037). Multivariate Cox analysis revealed that failure of remission at the first 6 months (hazard ratio [HR] = 5.769; 95% CI [1.854-17.950]; P = 0.002) remained an independent risk factor for poor renal outcome in patients with IMN.

Grading of renal ectopic lymphoid tissues correlates with disease activity and severity in IMN patients and can be used as an indicator to assess the risk of IMN progression.

Background: Chronic kidney disease (CKD) and heart failure (HF) are interrelated conditions that exacerbate each other through mechanisms like fluid retention, neurohormonal activation, and inflammation. Red blood cell distribution width (RDW), a measure of red blood cell size variability, has emerged as a potential prognostic marker in HF. This study aimed to assess the prognostic value of RDW in HF patients, both with and without CKD, focusing on all-cause mortality and HF rehospitalizations. Methods: This observational retrospective study included 171 patients hospitalized for acute decompensated HF in a tertiary university hospital in Greece. Patients were divided into two groups based on their estimated glomerular filtration rate (eGFR), as Group 1 (eGFR < 60 mL/min/1.73 m2) and Group 2 (eGFR ≥ 60 mL/min/1.73 m2). RDW was measured upon admission, and outcomes of interest were all-cause mortality and HF rehospitalizations over a median follow-up period of 6.1 months. Statistical analyses included Kaplan-Meier survival curves, whereas the discrimination traits of RDW were evaluated by constructing receiver operating characteristic (ROC) curves and by calculating the area under the ROC curve (AUC). A p-value <0.05 was indicative of a statistically important result. Results: Patients in Group 1 (eGFR < 60 mL/min/1.73 m2) were older (80 (73-86) vs. 75 (62-83)) and manifested higher median RDW values (16.6 (15.0-18.8) vs. 15.6 (14.1-17.8)) and received less frequent (57.9% vs. 75%) mineralocorticoid receptor antagonists (MRAs) as compared to those in Group 2 (eGFR ≥ 60 mL/min/1.73 m2). RDW demonstrated better prognostic value in predicting combined mortality and rehospitalization outcomes in Group 2 patients (area under the curve: 0.70; 95% CI (0.62-0.80)) compared to those in Group 1 (area under the curve: 0.53; 95% CI (0.35-0.72)). No statistically significant differences (p = 0.579) were observed in survival between patients with high (≥15%) and low (<15%) RDW values in the overall population, though trends favored worse outcomes with elevated RDW. Similarly, no significant differences (p = 0.374) were observed in survival between patients with high (Group 2) and low (Group 1) eGFR values. Conclusions: RDW appears to be a meaningful prognostic biomarker for HF patients, particularly in those without CKD. Further multicenter studies are needed to validate its clinical utility and potential for guiding treatment in this high-risk population.

Chronic kidney disease (CKD) affects approximately 14% of adults in the United States and is present in at least 10% of the population worldwide. Blood glucose and blood pressure control are imperative to adequately manage CKD as they are the only primary prevention measures for the condition. Recent changes in CKD evaluation and medication therapies that modify disease progression and aid in managing complications such as anemia of CKD have emerged, including a newly approved mineralocorticoid receptor antagonist and hypoxia-inducible factor-prolyl hydroxylase inhibitor, respectively. This focused update on CKD evaluation and management will review the most recent evidence and approved agents to support patients with CKD, including a review of glomerular filtration rate measurement methods such as CKD-EPI 2021 and utilization of cystatin C, Kidney Disease Improving Global Outcomes (KDIGO) guidelines, American Diabetes Association (ADA) guidelines, and primary literature supporting the use of newer agents in CKD. Checklists for managing blood pressure and blood glucose, CKD-mineral bone disorder, and anemia of CKD targeted for pharmacists are also provided. Additionally, a discussion of Centers for Medicare & Medicaid (CMS) coverage of agents approved for managing complications of CKD is included.

Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, has proven efficacy in the treatment of renal anemia; however, evidence indicates that it may cause central hypothyroidism. The prevalence and reversibility of roxadustat-induced central hypothyroidism in patients undergoing hemodialysis remain unclear. Here, we retrospectively analyzed thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels in 51 patients (mean age: 72.3 ± 10.7 years; 58.8% male) undergoing hemodialysis before, during, and after halting roxadustat treatment. TSH levels were significantly decreased from a median of 2.46 (interquartile range:1.60-4.51) mU/L before roxadustat treatment to 1.36 (0.72-2.41) mU/L during treatment (p < 0.001), and improved to 2.56 (1.78-4.63) mU/L after halting roxadustat (p < 0.001). Similarly, FT4 levels decreased from 1.11 (0.97-1.24) ng/dL before roxadustat treatment to 0.92 (0.71-1.03) ng/dL during treatment (p < 0.001) and improved to 1.05 (0.93-1.17) ng/dL after halting roxadustat (p < 0.001). FT3 levels were 2.04 (1.78-2.31) pg/mL before starting roxadustat, 1.97 (1.69-2.27) pg/mL during treatment, and 1.90 (1.63-2.18) pg/mL after halting roxadustat, with no significant difference between each group. Moreover, 2.0% of patients exhibited extremely low TSH levels (≤0.1 mU/L) and low TSH levels (>0.1 mU/L to <0.4 mU/L) before starting roxadustat and that percentage increased to 5.9% and 7.8%, respectively, during treatment. After roxadustat cessation, extremely low or low TSH levels recovered in all patients. Taken together, the results indicate that roxadustat can cause reversible central hypothyroidism in patients undergoing hemodialysis.

Anemia is a common complication of chronic kidney disease with major option treatment of erythropoiesis-stimulating agents (ESAs). This study aimed to investigate the influencing factors of erythropoietin resistance index (ERI) and its association with mortality in maintenance hemodialysis (MHD) patients. Patients enrolled from China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 were included. ERI was calculated as follows: ESA (IU/week)/weight (kg, post-dialysis)/hemoglobin level (g/dL). The Cox regression model was used to analyze the influencing factors on survival outcomes. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were performed. A total of 1270 MHD subjects (687 males and 583 females) were included, with an average age of 60 (49.0, 71.0) years. All subjects were divided into two groups by the median ERI of 14.03. Multivariate logistic regression showed that dialysis vintage (OR 0.957, 95% CI: 0.929-0.986), white blood cells (OR 0.900, 95% CI: 0.844-0.960), high flux dialyzer use (OR 0.866, 95% CI: 0.755-0.993), body mass index (OR 0.860, 95% CI: 0.828-0.892), males (OR 0.708, 95% CI: 0.625-0.801), and albumin (OR 0.512, 95% CI: 0.389-0.673) had a negative association with high ERI baseline (all p < 0.05). There were 176 (13.9%) deaths in total including 89 cardiac/vascular deaths during follow-up. Cox regression analysis showed that ERI was positively associated with all-cause mortality, especially in some subgroups. ERI was associated with increased all-cause mortality in MHD patients, indicating the possibility of death prediction by ERI. Patients with high ERI warrant more attention.

Bone homeostasis is balanced between formation and resorption activities and remain in relative equilibrium. Under disease states this process is disrupted, favoring more resorption over formation, leading to significant bone loss and fracture incidence. This aspect is a hallmark for patients with chronic kidney disease mineral and bone disorder (CKD-MBD) affecting a significant portion of the population, both in the United States and worldwide. Further study into the underlying effects of the uremic microenvironment within bone during CKD-MBD are critical as fracture incidence in this patient population not only leads to increased morbidity, but also increased mortality. Lack of bone homeostasis also leads to mineral imbalance contributing to cardiovascular calcifications. One area understudied is the possible involvement of bone marrow adipose tissue (BMAT) during the progression of CKD-MBD.

BMAT accumulation is found during aging and in several disease states, some of which overlap as CKD etiologies. Importantly, research has found presence of BMAT inversely correlates with bone density and volume. Understanding the underlying molecular mechanisms for BMAT formation and accumulation during CKD-MBD may offer a potential therapeutic avenue to improve bone homeostasis and ultimately mineral metabolism.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of agents for the treatment of anemia in chronic kidney disease (CKD). Unlike traditional treatments such as erythropoiesis-stimulating agents (ESAs), HIF-PH inhibitors are orally administered drugs and may increase endogenous erythropoietin and improve iron homeostasis. However, a significant concern is their possible side effect on blood pressure. The current mini-review summarizes the data of 26 randomized controlled (placebo or ESAs) trials on six different HIF-PH inhibitors with regard to their potential influence on blood pressure and hypertension in the management of anemia in CKD. Overall, the use of HIF-PH inhibitors was associated with a higher risk of hypertension than placebo (pooled risk ratio 1.36, 95% confidence interval [CI] 1.16-1.59), but a lower risk of hypertension than ESA treatment (pooled risk ratio 0.92, 95% CI 0.86-0.98), especially in CKD patients not undergoing dialysis (pooled risk ratio 0.85, 95% CI 0.73-0.98). This review highlights the importance of blood pressure monitoring during the treatment of HIF-PH inhibitors, especially out-of-office blood pressure measurement.

The kidney is the main organ that senses changes in systemic O2 pressure by hypoxia-PHD-HIFa (HPH) signaling, resulting in adaptive target gene activation, including erythropoietin (EPO). The non-essential transition metal cadmium (Cd) is nephrotoxic and disrupts the renal HPH pathway, which may promote Cd-associated chronic renal disease (CKD). A deeper molecular understanding of Cd interference with renal HPH signaling is missing, and no data with renal cell lines are available. In rat kidney NRK-52E cells, which model the proximal tubule, and murine fibroblastoid atypical interstitial kidney (FAIK3-5) cells, which mimic renal EPO-producing cells, the chemical hypoxia mimetic dimethyloxalylglycine (DMOG; 1 mmol/l) or hypoxia (1% O2) activated HPH signaling. Cd2+ (2.5-20 µmol/l for ≤ 24 h) preferentially induced necrosis (trypan blue uptake) of FAIK3-5 cells at high Cd whereas NRK-52E cells specially developed apoptosis (PARP-1 cleavage) at all Cd concentrations. Cd (12.5 µmol/l) abolished HIFa stabilization and prevented upregulation of target genes (quantitative real-time polymerase chain reaction and immunoblotting) induced by DMOG or hypoxia in both cell lines, which was caused by the formation of insoluble HIFa aggregates. Strikingly, hypoxic preconditioning (1% O2 for 18 h) reduced apoptosis of FAIK3-5 and NRK-52E cells at low Cd concentrations and decreased insoluble HIFa proteins. Hence, drugs mimicking hypoxic preconditioning could reduce CKD induced by chronic low Cd exposure.

Anemia and mineral and bone disorder (MBD) are significant complications of chronic kidney disease (CKD). The erythropoietin (Epo) pathway plays a key role in both of these processes in CKD. Another molecule that plays an important role in CKD-MBD is fibroblast growth factor (FGF)-23, whose main role is to maintain serum phosphate levels in the normal range, acting via its co-receptor Klotho; however, its activity may also be related to anemia and inflammation. In this review, the regulation of Epo and FGF-23 and the molecular mechanisms of their action are outlined. Furthermore, the complex interaction between EPO and FGF-23 is discussed, as well as their association with other anemia-related factors and processes such as Klotho, vitamin D, and iron deficiency. Together, these may be part of a "kidney-bone marrow-bone axis" that promotes CKD-MBD.

Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented.

We investigated sex-specific disparities in CKD-related complications and mortality according to estimated glomerular filtration rate (eGFR) levels. We analyzed National Health and Nutrition Examination Survey (NHANES) data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 mL/min/1.73 m2. The outcomes were CKD-related complications [hypertension, anaemia, cardiovascular (CV) diseases, acidosis, hyperphosphatemia, hyperparathyroidism] and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios and hazard ratios for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance.

The study included 49 558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR-hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women).

Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier; women show a steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Patients undergoing hemodialysis (HD) for chronic kidney disease (CKD) often encounter anemia. Roxadustat has not only undergone phase II-III clinical trials in patients suffering from CKD and undergoing HD; a number of post-marketing clinical studies have been conducted using the drug. This article was to assess the effectiveness and safety of roxadustat in managing anemia among patients with CKD undergoing HD.

A thorough search was performed across eight databases, including PubMed, Web of Science, Cochrane Library, Embase, Wan Fang, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQ VIP), and SinoMed to identify randomized clinical trials (RCTs) examining the effectiveness and safety of roxadustat in managing anemia among individuals suffering from CKD and undergoing HD. This search included studies from the inception of these databases to April 2023.

Two phase II, one phase III, and 16 post-marketing studies with 1688 participants were included. Serum iron (SI), transferrin, and total iron-binding capacity (TIBC) levels changed from baseline (∆SI, ∆transferrin, and ∆TIBC) and were significantly more increased for roxadustat than for erythropoiesis-stimulating agents (ESAs): MD 2.55, (95% CI 1.51 to 3.60), p < 0.00001; MD 0.55, (95% CI 0.41 to 0.69), p < 0.00001; and MD 6.54, (95% CI 4.50 to 8.59), p < 0.00001, respectively. Roxadustat was not inferior to ESAs with regard to increasing Hb (∆Hb) levels [MD 1.17 (95% CI 0.71 to 1.63), p < 0.00001] (g/dL). No statistically significant distinctions of the ∆ferritin, ∆hepcidin, and transferrin saturation (TSAT) from baseline (∆TSAT) level were identified between roxadustat and ESAs. C-reactive protein (CRP) levels changed from baseline (∆CRP) and were significantly more reduced for roxadustat than for ESAs. As for safety, the analysis indicated no notable difference in the occurrence of adverse events (AEs) and serious adverse events (SAEs) between roxadustat and ESAs.

This meta-analysis demonstrated that roxadustat outperformed ESAs in enhancing SI, transferrin, and TIBC levels while also decreasing CRP levels. Roxadustat was not inferior to ESAs in terms of improving Hb levels and safety. These findings suggest that roxadustat was well tolerated and a potent alternative to ESAs in managing anemia among patients suffering from CKD and undergoing HD.

Artificial intelligence (AI)-based multi-modal fusion algorithms are pivotal in emulating clinical practice by integrating data from diverse sources. However, most of the existing multi-modal models focus on designing new modal fusion methods, ignoring critical role of feature representation. Enhancing feature representativeness can address the noise caused by modal heterogeneity at the source, enabling high performance even with small datasets and simple architectures. Here, we introduce DeepOmix-FLEX (Fusion with Learning Enhanced feature representation for X-modal or FLEX in short), a multi-modal fusion model that integrates clinical data, proteomic data, metabolomic data, and pathology images across different scales and modalities, with a focus on advanced feature learning and representation. FLEX contains a Feature Encoding Trainer structure that can train feature encoding, thus achieving fusion of inter-feature and inter-modal. FLEX achieves a mean AUC of 0.887 for prediction of chronic kidney disease progression on an internal dataset, exceeding the mean AUC of 0.727 using conventional clinical variables. Following external validation and interpretability analyses, our model demonstrated favorable generalizability and validity, as well as the ability to exploit markers. In summary, FLEX highlights the potential of AI algorithms to integrate multi-modal data and optimize the allocation of healthcare resources through accurate prediction.

Anemia management in chronic kidney disease (CKD) is a significant challenge for healthcare professionals worldwide. The extensive management of CKD and its complications is directly linked with a substantial treatment burden, which impacts quality of life (QoL). This study aimed to assess the prevalence and management of anemia and to evaluate the treatment burden and its impact on the QoL of CKD and dialysis patients in Pakistan.

A multicenter prospective observational study was conducted in three hospitals. A total of 170 patients were enrolled, with 156 available for follow-up after six months. Their prior consent was obtained. Each participant was interviewed in person and received a data collection form.

At baseline, the prevalence of anemia among CKD (stage 3-5) and dialysis patients was 78.7% and 94.7%, respectively. Patients on dialysis used more erythropoietin stimulating agents (ESAs), with 38.6% at baseline and 40.8% by month six, compared to non-dialysis CKD patients. Oral iron was used by 6.2% of stage 3, 25% of stage 4, 20% of stage 5 patients, and 6.6% of dialysis patients at baseline. At the six-month follow-up, 42.8% of CKD and 33.8% of dialysis patients achieved the target hemoglobin level. Dialysis patients had a higher treatment burden compared to CKD at baseline (77.4±10.6 vs 59.3±13.3) and at six-month visit (79.3±11.1 vs 59.1±14.5). The multiple regression analysis showed that treatment burden had a significant association with age, disease duration, and comorbidity at baseline. There was a significant negative correlation between overall treatment burden and QoL, indicating that QoL decreases as treatment burden increases.

Anemia was prevalent, and its management was suboptimal in this study. The overall treatment burden score was high in dialysis patients, negatively affecting the QoL.

Urothelial carcinoma (UC) predominantly arises in the bladder, but upper tract urothelial carcinomas (UTUCs) comprise 5-10% of cases. Patients with end-stage renal disease (ESRD) are at increased risk for UC, and erythropoiesis-stimulating agents (ESAs) are frequently used to manage anemia in ESRD. However, ESA use in cancer patients raises concerns about tumor progression and survival outcomes. This study aimed to assess the impact of ESA use on tumor recurrence, cancer-specific survival (CSS), and overall survival (OS) in patients with ESRD and early-stage UC. We analyzed data from the Chang-Gung Research Database (CGRD) in Taiwan, including 850 patients with ESRD and non-muscle-invasive bladder cancer (NMIBC) and 492 patients with ESRD and localized UTUC. The ESA group was compared to a non-ESA cohort, and inverse probability of treatment weighting (IPTW) was applied to minimize selection bias. Kaplan-Meier curves and log-rank tests were used to evaluate bladder recurrence-free survival, CSS, and OS. In NMIBC patients, ESA use did not significantly affect bladder recurrence-free survival, CSS, or OS. Similarly, ESA use in localized UTUC patients did not increase the risk of bladder recurrence or negatively impact CSS and OS. However, UTUC patients treated with ESA demonstrated a significantly increased risk of contralateral recurrence (P < 0.001). The use of ESA in patients with ESRD and early-stage UC appears safe regarding bladder recurrence, CSS, and OS, but clinicians should remain vigilant for contralateral recurrence in localized UTUC. These findings provide valuable insights into the complex management of anemia in patients with concurrent ESRD and UC, emphasizing the need for tailored clinical monitoring in this high-risk population.

This study tested whether combined dapagliflozin (DAPA) and roxadustat (ROX) therapy was superior to a singular therapy in protecting heart and kidney functions in rats with cardiorenal syndrome (CRS).

An in vitro study demonstrated that the cell survival (PI3K/Akt/mTOR)/cell stress (ERK1/2, JNK/p-38) signaling was significantly activated by combination therapy with ROX-DAPA (all p<0.001). Additionally, these two signaling pathways further significantly upregulated the hypoxia-induced factor (HIF)-1α which, in turn, significantly upregulated Nrf2/ARE (HO-1/NQO-1) and angiogenesis/cell-growth factors (EPO/SDF-1α/VEGF/FGF/IGF-2) and downregulated hypoxia-inducible factor prolyl-4-hydroxylase-1 (all p<0.001). Adult-male SD rats were categorized into Groups 1 (sham-operated control)/2 (CRS)/3 (CRS+ROX)/4 (CRS+DAPA)/5 (CRS+ROX+DAPA). By Day 60 after rodent CRS induction, the levels of BUN/creatinine and the ratio of urine protein to creatinine were lowest in Group 1, highest in Group 2, and significantly lower in Group 5 than in Groups 3 and 4; however, they were similar in the latter two groups, whereas the left-ventricular-ejection-fraction exhibited the opposite trend of creatinine among the groups (all p<0.0001). The protein expression levels of cell-survival (p-PI3K/p-Akt-p-mTOR)/cell-stress (p-JNK/p-p38/p-ERK1/2)/Nrf2-ARE (HO-1/NQO-1/SIRT1/SIRT3) signaling factors and angiogenesis factors (HIF-1α/VEGF/SDF-1α/FGF/IGF-2/EPO) significantly and progressively increased from Groups 1-5 (all p<0.0001).

Combined DAPA-ROX therapy has a synergistic effect on protecting heart and kidney functions against CRS-induced damage in rodents.

Five hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been approved for marketing in Japan. However, marked differences exist in terms of drug potency, dose requirement, and pharmacokinetics.