Anemia Of Chronic Disease Research Articles

Chemistry, Analysis, and Biological Aspects of Daprodustat, A New Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitor: A Comprehensive Review.

The National Health and Nutrition Examination Survey (NHANES) carried out a survey between 2007-10 and found that as compared to the general population, the prevalence of anemia in chronic kidney disease (CKD) patients was twice high. Daprodustat is an investigational novel drug for the treatment of renal anemia. The objective of this study is to provide a comprehensive review of chemistry, synthesis, pharmacology, pharmacokinetic, and bioanalytical methods for the analysis of Daprodustat. To improve understanding, a review was carried out by creating a database of relevant prior research from electronic sources such as ScienceDirect and PubMed. The methodology is shown in the flowchart of the literature selection process. The drug was approved in 2020 for therapeutic purposes in Japan. It is a novel drug approved for the treatment of anemia in chronic kidney disease for oral administration. It is intended for adults who have undergone dialysis for a minimum of four months and are experiencing anemia as a result of chronic kidney disease. This review examines therapeutic, pharmacological, and analytical aspects related to the novel drug Daprodustat.

Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope?

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.

Multiple roles of mitochondrial autophagy receptor FUNDC1 in mitochondrial events and kidney disease.

This article reviews the latest research progress on the role of mitochondrial autophagy receptor FUN14 domain containing 1 (FUNDC1) in mitochondrial events and kidney disease. FUNDC1 is a protein located in the outer membrane of mitochondria, which maintains the function and quality of mitochondria by regulating mitochondrial autophagy, that is, the selective degradation process of mitochondria. The structural characteristics of FUNDC1 enable it to respond to intracellular signal changes and regulate the activity of mitochondrial autophagy through phosphorylation and dephosphorylation. During phosphorylation, unc-51-like kinase 1 (ULK1) promotes the activation of mitophagy by phosphorylating Ser17 of FUNDC1. In contrast, Src and CK2 kinases inhibit the interaction between FUNDC1 and LC3 by phosphorylating Tyr18 and Ser13, thereby inhibiting mitophagy. During dephosphorylation, PGAM5 phosphatase enhances the interaction between FUNDC1 and LC3 by dephosphorylating Ser13, thereby activating mitophagy. BCL2L1 inhibits the activity of PGAM5 by interacting with PGAM5, thereby preventing the dephosphorylation of FUNDC1 and inhibiting mitophagy. FUNDC1 plays an important role in mitochondrial events, participating in mitochondrial fission, maintaining the homeostasis of iron and proteins in mitochondrial matrix, and mediating crosstalk between mitochondria, endoplasmic reticulum and lysosomes, which have important effects on cell energy metabolism and programmed death. In the aspect of kidney disease, the abnormal function of FUNDC1 is closely related to the occurrence and development of many diseases. In acute kidney injury (AKI), cardiorenal syndrome (CRS), diabetic nephropathy (DN), chronic kidney disease (CKD) ,renal fibrosis (RF) and renal anemia, FUNDC1-mediated imbalance of mitophagy may be one of the key factors in disease progression. Therefore, in-depth study of the regulatory mechanism and function of FUNDC1 is of great significance for understanding the pathogenesis of renal disease and developing new treatment strategies.

Erythropoietin levels in geriatric anemia

ABSTRACT Background: Defects in the production or action of erythropoietin (EPO) are important contributing factors in anemia. However, the exact impact of aging on levels of EPO and its role in the development of geriatric anemia is still underexplored. Moreover, the specific pattern of EPO in etiological subcategories such as nutritional anemia (NA), anemia of chronic disease (ACD), and unexplained anemia (UA) is not entirely known. Objective: The aim of the study was to determine the serum EPO levels in geriatric anemia and compare them across NA, ACD, UA, and NA with ACD. Materials and Methods: Ninety anemic geriatric patients (cases) along with 30 non-anemic geriatric controls were evaluated for serum EPO levels. A correlation between S.EPO and inflammatory markers was also done. Results: Serum EPO levels were higher in cases as compared to controls (P < 0.00). After adjusting for outliers, the reference range of EPO in controls was the same as in normal young adults (2.21–20.95 mU/mL). The majority (37/58, 63.7%) of NA patients had increased S.EPO levels (highest among all four subcategories and controls). S.EPO also correlated inversely with high-sensitivity CRP (hsCRP) and serum ferritin (SF), reinforcing that the inflammatory state suppresses S.EPO levels. Conclusion: Geriatric anemic patients have elevated S.EPO as compared to non-anemic controls (observed reference range similar to young adults). Raised EPO levels were detected more frequently in NA, while they were the lowest in UA.

October 2024 Critical Care Case of the Month: Respiratory Failure in a Patient with Ulcerative Colitis

No abstract available. Manuscript truncated after 150 words. History of Present Illness The patient is a 57-year-old woman with a history of ulcerative colitis (UC) complicated by toxic megacolon with subsequent colectomy. She presented to the emergency department with cough, shortness of breath and hypoxemia (87% on RA). PMH, SH • UC with history of toxic megacolon (4 years prior) with a total colectomy • History of a prior episode of respiratory failure a year earlier thought possibly medication induced (ustekinumab, Stelara®) which she was taking for her UC. She was treated with steroids at that time with good response. • Pyoderma gangrenosum of both ankles (attributed to UC). • Anemia of chronic disease. • She is a lifelong non-smoker. • No exposures to toxic dusts, birds, down, humidifiers, mold or other antigens associated with hypersensitivity pneumonitis. Physical Exam • Afebrile, Oxygen saturation 94% on 2 lpm supplemental oxygen. • Chest: crackles noted at left base. • CV regular rhythm, no murmur. Ext: scarring and erythema on …

Adaptability of clinical pharmacist led interventions in the management of anemia of chronic renal disease: optimizing care

Renal anemia is a common comorbidity in chronic kidney disease (CKD) patients, typically treated with erythropoiesis-stimulating agents (ESAs) like erythropoietin. However, both over- and under-treatment are prevalent. In 2008, the Pharmacy Council of India introduced the Pharm.D course to enhance pharmaceutical care in clinical settings. While extensive studies in other countries highlight the benefits of clinical pharmacists' interventions, Indian research on this topic is limited. This prospective randomized controlled trial included CKD patients not on dialysis, with serum creatinine levels of 2-6 mg/dL and hemoglobin (Hb) levels below 12 g/dL. Participants were divided into three subgroups based on baseline Hb levels: < 10 g/dL (Group I), 10-12 g/dL (Group II), and >12 g/dL (Group III). ESAs and iron supplements were adjusted to maintain Hb levels of 10-12 g/dL. Quality of life was assessed using the Short Form Health Survey-36 questionnaire. Out of 448 participants, those in the pharmacist intervention group showed a significant shift towards Group II by the trial's end, compared to the control group. The study demonstrated a significant improvement in quality of life and physical performance, particularly for those in Group II, indicating that maintaining Hb levels at 10-12 g/dL is optimal for Indian CKD patients. This trial exemplifies the profound impact clinical pharmacists can have on patient care, highlighting their crucial role in improving healthcare outcomes through active participation and targeted interventions in clinical settings.

CHRONIC HEART FAILURE EPIDEMIOLOGY IN KAZAKHSTAN AND OTHER COUNTRIES

The article discusses the etiologic factors contributing to chronic heart failure (CHF) development, as well as CHF main causes. Statistics on CHF prevalence and mortality in Kazakhstan over the past decades is presented in brief. Clinical guidelines of the Kazakhstan Cardiology Society describe many risk factors for CHF in detail, including both underlying and concomitant diseases. According to statistics, 4.7 % of Kazakhstan population (approximately 320,000 people) suffer from CHF. The most common causes or concomitant diseases contributing to CHF development are arterial hypertension, coronary heart disease, chronic kidney disease, atrial fibrillation, postinfarction cardiosclerosis, diabetes mellitus, obesity, malignant neoplasms, chronic obstructive pulmonary disease and chronic anemia. The highest incidence of cardiovascular diseases (CVD) is observed in Almaty – 4 %. Mortality from circulatory system diseases in the Republic of Kazakhstan decreased from 207.4 cases per 100,000 people in 2012 to 178.92 cases in 2016. Differences in approaches to CHF coding in the structure of clinical and pathological diagnosis significantly affect data accuracy on CHF prevalence and mortality. These differences are due to the fact that CHF is not an independent disease; it is rather a complication. When we speak about CHF as a disease, we usually consider it as a deuteropathy. Thus, CHF often does not have a code in the structure of the lifetime diagnosis and it is not considered as the primary cause of death in the case of fatality. As a result, we understand the significant impact of CHF on mortality, but do not have an accurate idea of the real scale of the problem.

Usage of the Anemia Control Model Is Associated with Reduced Hospitalization Risk in Hemodialysis.

The management of anemia in chronic kidney disease (CKD-An) presents significant challenges for nephrologists due to variable responsiveness to erythropoietin-stimulating agents (ESAs), hemoglobin (Hb) cycling, and multiple clinical factors affecting erythropoiesis. The Anemia Control Model (ACM) is a decision support system designed to personalize anemia treatment, which has shown improvements in achieving Hb targets, reducing ESA doses, and maintaining Hb stability. This study aimed to evaluate the association between ACM-guided anemia management with hospitalizations and survival in a large cohort of hemodialysis patients. This multi-center, retrospective cohort study evaluated adult hemodialysis patients within the European Fresenius Medical Care NephroCare network from 2014 to 2019. Patients treated according to ACM recommendations were compared to those from centers without ACM. Data on demographics, comorbidities, and dialysis treatment were used to compute a propensity score estimating the likelihood of receiving ACM-guided care. The primary endpoint was hospitalizations during follow-up; the secondary endpoint was survival. A 1:1 propensity score-matched design was used to minimize confounding bias. A total of 20,209 eligible patients were considered (reference group: 17,101; ACM adherent group: 3108). Before matching, the mean age was 65.3 ± 14.5 years, with 59.2% men. Propensity score matching resulted in two groups of 1950 patients each. Matched ACM adherent and non-ACM patients showed negligible differences in baseline characteristics. Hospitalization rates were lower in the ACM group both before matching (71.3 vs. 82.6 per 100 person-years, p < 0.001) and after matching (74.3 vs. 86.7 per 100 person-years, p < 0.001). During follow-up, 385 patients died, showing no significant survival benefit for ACM-guided care (hazard ratio = 0.93; p = 0.51). ACM-guided anemia management was associated with a significant reduction in hospitalization risk among hemodialysis patients. These results further support the utility of ACM as a decision-support tool enhancing anemia management in clinical practice.

Anemia of Chronic Disease and Chronic Periodontitis: Estimation of Hematological Status and its Correlation with Clinical Parameters

Anemia of Chronic Disease and Chronic Periodontitis: Estimation of Hematological Status and its Correlation with Clinical Parameters

Assessment of hepcidin in Egyptian patients with rheumatoid arthritis and its relation to anemia: a single-center study

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disorder characterized by synovial inflammation that leads to joint damage, bony erosions, and related deformities. Between 30 and 70% of RA patients will experience anemia. Early detection of anemia is of great importance. This study aimed to evaluate the serum level of hepcidin (HEP) in RA patients and to assess its relation to disease activity and anemia. The current cross-sectional study included 44 cases with RA in addition to 44 healthy controls. The disease activity in the RA patient was assessed by using the disease activity score (DAS) 28 score-CRP. The serum levels of HEP and ferritin were assessed in both groups using enzyme-linked immunosorbent assay (ELISA) technique.ResultsHepcidin level in the RA group was statistically significantly higher as compared to the control group (p = 0.001). The prevalence of Anemia of chronic disease (ACD) was 40.9%, and iron deficiency anemia (IDA) was 27.3% which accounted for 68.2% of the total anemia cases. The HEP level was statistically significantly higher in the RA patients with ACD than those without anemia (P = 0.028), RA patients with IDA (P < 0.001), and control group (P < 0.001). There was a statistically significant positive correlation between HEP level and serum ferritin level (p = 0.005). HEP level was significantly and inversely correlated with hemoglobin (Hb) in patients with ACD. Serum HEP level is higher in RA patients with high disease activity than those with moderate activity, low activity, and patients in remission (p = 0.380). However, the difference was not statistically significant. The best cutoff point of HEP level to identify RA patients from healthy controls was > 355.5 Pg/ml. This point showed moderate sensitivity (70.5%) with moderate specificity (63.6%) with a statistically significant value.ConclusionsWe found the anemia, and particularly ACD, is more common in RA patients. In RA patients with ACD, serum HEP levels were considerably higher. Although serum HEP showed no diagnostic significance when it came to evaluating disease activity, it could be a dependable non-invasive biomarker for the diagnosis of various forms of anemia in RA patients.

Inflammatory indexes and anemia in chronic kidney disease: correlation and survival analysis of the National Health and Nutrition Examination Survey 2005–2018

Background There is currently no research on the correlation between novel inflammatory indexes systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the risk of anemia in chronic kidney disease (CKD) population, as well as survival analysis in CKD with anemia. Methods This investigation encompassed 4444 adult subjects out of the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The study utilized multi-variable logistic regression to assess the relationship between SII, NLR, PLR, and anemia risk occurrence in CKD population. Survival differences in CKD patients with anemia, based on varying levels of SII, NLR, and PLR were evaluated employing Kaplan–Meier and Cox proportional hazards models. Results The adjusted logistic regression model demonstrates that SII, NLR, and PLR are associated with the risk of anemia occurrence in CKD population. Kaplan–Meier’s analysis reveals significant differences in survival rates among CKD patients with anemia stratified by NLR levels. The adjusted Cox proportional hazards model shows that the higher NLR group has a 30% elevated risk of all-cause mortality contrasted with lower group (hazard ratio, HR: 1.30, confidence interval (CI) [1.01, 1.66], p value <.04). Restricted cubic spline (RCS) demonstrates no nonlinear relationship between NLR and all-cause mortality. Lastly, sub-cohort analysis indicates that in populations with diabetes, hypertension, and hyperuricemia, NLR levels have a greater impact on all-cause mortality. Conclusions Controlling inflammation may reduce the occurrence of anemia in CKD populations, with NLR serving to be a potential prognostic indicator for survival results within CKD patients suffering from co-morbid anemia.

Successful Management of Miliary Tuberculosis with Concomitant Anemia: A Case Report

Background: Miliary tuberculosis (TB) is a disseminated and potentially fatal form of TB characterized by the hematogenous spread of Mycobacterium tuberculosis, often complicated by anemia of chronic disease. The diagnosis and management of miliary TB, particularly in conjunction with anemia, can be challenging, especially in resource-limited settings. Case presentation: We report the case of a 20-year-old male from a remote region in Eastern Halmahera, Indonesia, who presented with progressive shortness of breath, productive cough, night sweats, unintentional weight loss, and generalized weakness. Clinical examination revealed signs of anemia and respiratory distress. Laboratory investigations confirmed microcytic hypochromic anemia and a positive GeneXpert MTB/RIF test. Chest radiography demonstrated diffuse miliary nodules, consolidation, and cavitation, establishing the diagnosis of miliary TB with concomitant anemia. The patient received a standard six-month anti-tuberculosis therapy regimen, along with supportive care and targeted treatment for anemia and associated symptoms. The patient demonstrated significant clinical and hematological improvement, leading to discharge after 11 days of hospitalization. Follow-up assessments confirmed continued progress and the absence of complications. Conclusion: This case underscores the critical importance of maintaining a high index of suspicion for miliary TB in patients presenting with respiratory and constitutional symptoms, even in the absence of traditional risk factors. The presence of anemia can further complicate the clinical picture. Prompt diagnosis through a combination of clinical assessment, laboratory investigations, and imaging studies, followed by the immediate initiation of appropriate treatment, including the management of anemia, is paramount for achieving favorable outcomes in patients with miliary TB. The case also emphasizes the necessity for comprehensive care and follow-up to ensure sustained recovery and prevent relapse.

Risk assessment tool for anemia of chronic disease in systemic lupus erythematosus: a prediction model.

This study aims to develop a predictive model for estimating the likelihood of anemia of chronic disease (ACD) in patients with systemic lupus erythematosus (SLE) and to elucidate the relationship between various factors and ACD METHODS: Individuals diagnosed with SLE for at least one year were enrolled and categorized into two groups: those with ACD and those without anemia symptoms. Patients were randomly assigned to training and test sets at an 8:2 ratio. The least absolute shrinkage and selection operator (LASSO) method was used to select predictors, followed by logistic regression for modeling. Model performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) for both training and test sets. The study included a total of 216 patients, with 172 in the training set and 44 in the test set. LASSO identified 6 variables for constructing the predictive model, resulting in an area under the curve (AUC) of 0.833 (95% CI, 0.773-0.892) in the training set and 0.861 (95% CI, 0.750-0.972) in the test set. Calibration curves indicated consistency between expected and observed probabilities. DCA indicated that the model yielded a net benefit with threshold probabilities ranging from 20% to 90% in the training set and from 10% to 80% in the test set. This study presents a predictive model for assessing the risk of ACD in SLE patients. The model effectively captures the underlying mechanism of ACD in SLE and empowers clinicians to make well-informed treatment adjustments. Key Points • Development of a New Predictive Model: This study introduces a new predictive model to evaluate the likelihood of anemia of chronic disease (ACD) in patients with systemic lupus erythematosus (SLE). The model utilizes routine laboratory parameters to identify high-risk individuals, addressing a significant gap in current clinical practice. • Reflection of Potential Mechanisms for ACD Development: By incorporating the factors needed to construct the predictive model, this study also sheds light on the potential mechanisms of ACD development in SLE patients.

Evaluating iron replacement therapies in pediatric CKD: A comparative analysis of oral liposomal iron, iron supported lactoferrin and IV iron Dextran

CKD is defined as longstanding kidney damage and reduction in renal function. The global burden of CKD in the pediatric population is 15 per million, with congenital renal anomalies and hereditary disorders being the primary causes. Of these, 10% of patients require RRT. The development of anemia in chronic disease is a significant concern as the disease progresses. This condition exacerbates the pathological state by increasing the risk of infection, inevitably resulting in mortality. The study aims to establish the comparative analysis of three types of iron replacement therapies including oral liposomal iron, iron supported lactoferrin and IV iron dextran by evaluating their safety and efficacy corresponding to the different stages of CKD in pediatric population. A comparison between all three variants of iron replacement therapy shows oral liposomal iron provides higher bioavailability and tolerance but effective only in lower CKD stages. In IV iron dextran, rapid iron store replenishment has been observed, but with significant side effects, including the risk of severe hypersensitivity reaction. Conversely, oral iron-supported lactoferrin has demonstrated a maximal iron recovery response after six months of therapy, but with frequent gastrointestinal side effects.

Renoprotective Effects of Daprodustat in Patients with Chronic Kidney Disease and Renal Anemia.

Many large-scale studies revealed that exogenous erythropoietin, erythropoiesis-stimulating agents, have no renoprotective effects. We reported the renoprotective effects of endogenous erythropoietin production on renal function in ischemic reperfusion injury (IRI) of the kidney using the prolyl hydroxylase domain (PHD) inhibitor, Roxadustat. The purpose of this study was to investigate the effects of daprodustat on the progression of chronic renal failure. We retrospectively investigated the effects of daprodustat on the progression of chronic renal failure and renal anemia in patients with stages 3a-5 chronic kidney diseases (estimated glomerular filtration rate, eGFR < 60 mL/min/1.73 m2). The results show that daprodustat largely slowed the reduction in eGFR. The recovery of renal function was observed in some patients. Daprodustat is useful not only for renal anemia but also for the preservation of renal function. The renoprotective effect of daprodustat was small in patients with serum creatinine larger than 3-4 mg/dL because of low residual renal function. The appearance of renal anemia would be a sign of the time to start using daprodustat.

RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease

The persistent production of inflammatory cytokines causes anemia of chronic disease (ACD). Playing a central role in the pathophysiology of ACD is hepcidin, a key regulator of iron metabolism. The regulation of hepcidin expression is a complex process intricately controlled by multiple pathways. These include the BMP/SMAD, the HFE–TFR2, and the IL-6/STAT3 pathway, each playing a significant role in this regulation. We detail the critical role of the repulsive guidance molecule (RGM) family, especially hemojuvelin (HJV/RGMc), in regulating hepcidin expression in ACD. HJV functions as a co-receptor for BMPs and positively regulates hepcidin expression. RGMa and RGMb may also regulate hepcidin expression and inflammatory responses. RGM family proteins play essential roles in the interplay between inflammation, iron metabolism, and the immune system, and elucidating them could lead to a better understanding of the pathophysiology of ACD and the development of new therapeutic strategies.

Profile of anemia in children with juvenile idiopathic arthritis

Background: Anemia is one of the commonest extra-articular manifestations or complications associated with juvenile idiopathic arthritis (JIA) and is generally seen to corelate with disease-duration and disease-activity. Aim of the study was to find out the prevalence of anemia, its etiological spectrum and severity in children suffering from JIA, to determine its correlation with disease-activity and disease-duration and assess the change in the status of anemia after initiating cause- specific treatment in addition to disease-specific treatment in a follow-up period of 3 months. Methods: This prospective longitudinal observational study was conducted in a tertiary care teaching hospital from July to December 2022. Patients of JIA were recruited through purposive sampling stratified by disease activity based on juvenile arthritis disease activity score (JADAS) 27 score and anemia categorized by World Health Organization (WHO) criteria. Results: A total of 64 children were included in the final analysis. Mean age of patients was 8.19 years (SD 2.34 years), male: female ratio being 1.2:1. 78.12% were anemic, with 59.37% being moderately anemic. Overall, anemia-of-chronic-disease (ACD) was the most (48%) prevalent type of anemia, followed by iron-deficiency-anemia (IDA) at 28%, followed by a combination of both IDA and ACD (12%). Remaining 12% was attributed to other causes of anemia. Mean-hemoglobin at 1st visit was found to decrease with increase in disease duration. Significant moderate linear negative correlation was found (r=-0.54) (p&lt;0.001) between mean-hemoglobin-at-1st-visit and mean-disease-activity-at-1st-visit. Significant rise in hemoglobin level after initiation of cause-specific treatment with disease-specific treatment was also observed in this study. Conclusions: Anemia associated with pediatric rheumatological conditions has significant negative impact on the disease process. Prompt diagnosis of anemia, denoting its type and severity, and thereby treating anemia alongside disease-specific treatment, significantly improves the patient outcome.

Serum hepcidin evaluation as a promising biomarker in juvenile idiopathic arthritis.

An important area of research in juvenile idiopathic arthritis (JIA) aims to identify sensitive and reliable biomarkers of disease activity. The key iron-regulatory hormone hepcidin-25 (HEP) has been advocated as a potential biomarker to assess anaemia of chronic disease and iron deficiency in adults with rheumatoid arthritis. We performed a cross-sectional study evaluating the utility of serum HEP in 79 non-systemic onset JIA patients (14 males, 65 females), with/without anaemia, determining its correlations with disease activity, assessed by the JIA Disease Activity Score (JADAS)-27, anaemia parameters, and iron status indices. Significant positive correlations for serum HEP levels were found with the JADAS-27 score (r=0.8988, p<0.0001), and significant differences were found in HEP serum levels between active and inactive patients (8.6 IQR 10.0 ng/mL vs. 2.9 IQR 1.9 ng/mL; p<0.0001). Mean serum HEP concentrations were significantly greater in high disease activity group than in others (p<0.0001). At the ROC curve, an HEP level >4.35 ng/mL discriminated subjects with active disease with a sensitivity of 91.8% and a specificity of 80.0% (AUC: 0.93; 95% CI: 0.88-0.98). Moreover, HEP levels were significantly higher in anaemic, iron repleted and active disease patients. HEP is associated with JIA disease activity, and it could be useful in early detection and monitoring of disease exacerbations. These findings highlight that inflammation plays a major role in HEP induction and point out that HEP could be directly implicated in the JIA inflammatory cascade.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in Kidney Disease

BackgroundHypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). In this systematic review and meta-analysis, we assessed long-term safety of HIF prolyl hydroxylase inhibitors.MethodsWe searched MEDLINE, Embase, and Cochrane databases for randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with greater than or equal to 48 weeks of follow-up. The primary outcome was major adverse cardiovascular event (MACE), defined as a composite of all-cause death, myocardial infarction, or stroke. Treatment effects were pooled using random-effects models.ResultsTwenty-five trials involving 26,478 participants were included. Of these, 13 trials enrolled 13,230 participants with dialysis-dependent CKD, and 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (risk ratio, 0.99; 95% confidence interval [CI], 0.92 to 1.08) or people with nondialysis-dependent CKD (risk ratio, 1.08; 95% CI, 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (risk ratio, 1.10; 95% CI, 0.96 to 1.27) in people with nondialysis-dependent CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE and cardiovascular death. Safety of HIF prolyl hydroxylase inhibitors for other outcomes was comparable with ESA in dialysis-dependent CKD. In nondialysis-dependent CKD, dialysis access thrombosis, venous thromboembolism, infections, and hyperkalemia occurred more frequently with HIF prolyl hydroxylase inhibitors in placebo-controlled trials but not in ESA-controlled trials.ConclusionsThere was no evidence of a difference in the long-term cardiovascular safety profile of HIF prolyl hydroxylase inhibitors and ESA in adults with dialysis-dependent CKD and adults with nondialysis-dependent CKD. (PROSPERO registration number, CRD42021278011.)

Inside ANEMIA of CKD: Projecting the Future Burden of Anemia of Chronic Kidney Disease and Benefits of Proactive Management: A Microsimulation Model of the Chinese Population.

Anemia is a common comorbidity of chronic kidney disease (CKD) that has been associated with increased risk of complications, healthcare expenditure, and reduced quality of life. In China, the treatment of anemia of CKD has been reported to be suboptimal in part because of a lack of awareness of the condition and its management. It is therefore important to raise awareness of the condition by estimating the future health and economic burden of anemia of CKD and also to understand how it may be addressed through proactive policies. This study aims to project the health and economic burden of anemia of CKD, in China, from 2023 to 2027 and to estimate the impact of a hypothetical intervention on related clinical and cost outcomes. A virtual Chinese population was simulated using demographic, clinical, and economic statistics within a validated CKD microsimulation model. Each individual was assigned a CKD stage, anemia stage, comorbidity status (type2 diabetes, hypertension), complication status (stroke, heart failure, and/or myocardial infarction), and a probability of receiving treatments and therapies. Annual direct healthcare costs were assigned and based on these factors. The hypothetical intervention reduced the prevalence of moderate and severe anemia by 5% annually. This hypothetical scenario was chosen to highlight the impact of implementing policies that could reduce anemia of CKD, and is aligned with the Healthy China 2030 policy, which aims to reduce mortality from noncommunicable diseases by 30%. Interventions could consist of early screening and intervention to reduce the escalation of anemia from mild to moderate or severe. Results were compared with a baseline "no change" scenario which reflects current trends. The number of patients with moderate/severe anemia of CKD was projected to increase from 3.0 to 3.2million patients, with associated costs increasing from ¥22.0 billion (B) to ¥24.4B between 2023 and 2027, respectively. Compared with the no change scenario, the hypothetical intervention reduced the prevalence of moderate and severe anemia of CKD, saving ¥3.9B in healthcare costs in 2027 (¥24.4B vs ¥20.6B, respectively). Consistent with trends in CKD burden in China, the prevalence of anemia of CKD is projected to increase, leading to greater related healthcare costs. The introduction of healthcare interventions designed to screen for and treat anemia more effectively could therefore reduce its future burden and related costs.