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.

Hematopoiesis and the behavior of hematopoietic stem and progenitor cells (HSPCs) are regulated by the bone marrow niche. Here, we introduce the major niche cell types in bone marrow and their response to stress condition. We highlight the hematopoietic response and bone marrow niche adaptation to inflammatory condition and non-hematopoietic diseases, which are not systematically summarized. These emerging data suggest targeting hematopoiesis and bone marrow niche may provide novel therapeutic target to precisely control the progression of the diseases.

This article profiles 27 innovative advancements in small-molecule drugs approved by the U.S. Food and Drug Administration (FDA) in 2024. These drugs target various therapeutic areas including non-small cell lung cancer, advanced or metastatic breast cancer, glioma, relapsed or refractory acute leukemia, urinary tract infection, Staphylococcus aureus bloodstream infections, nonalcoholic steatohepatitis, primary biliary cholangitis, Duchenne muscular dystrophy, hypertension, anemia due to chronic kidney disease, extravascular hemolysis, primary axillary hyperhidrosis, chronic obstructive pulmonary disease, severe alopecia areata, WHIM syndrome, Niemann-Pick disease type C, schizophrenia, supraventricular tachycardia, congenital adrenal hyperplasia, and cystic fibrosis. Among these approved small-molecule drugs, those with unique mechanisms of action and designated as breakthrough therapies by the FDA represent a significant proportion, highlighting ongoing innovation. Notably, eight of these drugs (including Rezdiffra®, Voydeya®, Iqirvo®, Voranigo®, Livdelzi®, Miplyffa®, Revuforj®, and Crenessity®) are classified as "first-in-class" and have received breakthrough therapy designation. These agents not only exhibit distinct mechanisms of action but also offer substantial improvements in efficacy for patients compared to prior therapeutic options. This article offers a comprehensive analysis of the mechanisms of action, clinical trials, drug design, and synthetic methodologies related to representative drugs, aiming to provide crucial insights for future pharmaceutical development.

Chronic kidney disease (CKD) presents a significant global health challenge, with anemia frequently manifesting in the more advanced stages. This study aimed to evaluate the global burden and cross-country inequality of CKD-related anemia from 1990 to 2021.

Data on CKD-related anemia were extracted from the Global Burden of Disease 2021 study. Trends in prevalence, years lived with disability (YLDs) and corresponding estimated annual percentage changes (EAPCs) from 1990 to 2021 were analyzed at global, regional and national levels. Health inequity analysis methodologies were employed to evaluate cross-country inequality based on sociodemographic index.

In 2021, global CKD-related anemia cases reached 63 751 624 [95% uncertainty interval (UI), 59 045 051-68 372 650], representing a 96.24% increase from 1990 (32 486 224; 95% UI 30 356 876-35 047 084). Notwithstanding this increase, global prevalence [EAPC -0.27; 95% confidence interval (CI) -0.34 to -0.21] and YLDs rates (EAPC -0.66; 95% CI -0.70 to -0.62) generally declined. Females were disproportionately affected, comprising 55.75% of prevalence cases and 65.87% of YLDs numbers in 2021. From 1990 to 2021, the burden increased in individuals with CKD-related anemia associated with type 1 diabetes. Significant cross-country inequalities in prevalence were observed and persisted [slope index of inequality: 255.04 (389.56-120.51) in 1990 to 423.30 (572.78-273.81) in 2021; health concentration index: -0.09 (-0.12 to -0.07) in 1990 to -0.14 (-0.17 to -0.11) in 2021].

Despite the global decline in prevalence and YLDs rates of CKD-related anemia, the number of cases continued to increase, and the burden disproportionately concentrated in less developed countries and territories. This investigation also revealed a gender disparity and the influence of specific causes.

Human donor kidneys release (pro)renin, erythropoietin (EPO), active vitamin D, and urodilatin during normothermic machine perfusion (NMP). However, whether the endocrine function of donor kidneys is associated with post-transplant kidney function is unclear.

We studied 28 donor kidneys, including seven from donation after brain death (DBD) donors and 21 from donation after circulatory death (DCD) donors. Prior to transplantation, we measured levels of (pro)renin, EPO, 1,25(OH)2D in the perfusate, and urodilatin in urine during NMP. Hormone release rates were compared between kidneys with and without delayed graft function (DGF), and correlations were assessed between hormone release rates and donor characteristics and transplant outcome, including DGF duration, serum creatinine levels at 1-week post-transplant, and estimated glomerular filtration rate at 1-month post-transplant.

DBD kidneys secreted significantly less EPO and more active vitamin D than DCD kidneys. Kidneys with DGF exhibited significantly higher release rates of active vitamin D and lower release rates of urodilatin compared to those without DGF. In addition, EPO release rate was positively correlated with serum creatinine levels at 1-week post-transplant. Finally, urodilatin release rates were negatively correlated with DGF duration and positively correlated with urine output.

Urodilatin release in urine and EPO and active vitamin D release in perfusate during NMP may serve as potential biomarkers for predicting early post-transplant outcomes.

ClinicalTrials.gov identifier: NCT04882254.

Renal dysfunction or Chronic kidney disease (CKD) are increasingly associated with cognitive deficit and memory impairment, suggesting a crucial kidney-brain axis. This review examines spironolactone's emerging role as a neuroprotective agent in the context of renal dysfunction-induced cognitive impairment. As a selective mineralocorticoid receptor (MR) antagonist, spironolactone demonstrates multifaceted protective mechanisms beyond its well established renoprotective effects. Evidences also suggests that spironolactone attenuates neuroinflammation, mitigates oxidative stress in brain, preserve blood-brain barrier (BBB) integrity and regulates hormonal imbalances associated with renal dysfunction. This review focuses on the reported beneficial effects of spironolactone in various neurodegenerative diseases (NDDs). These mechanisms collectively protect against the neurodegeneration in memory impairment induced by renal dysfunction. The dual action of spironolactone on both renal and cerebral tissues presents a novel therapeutic advantage in addressing this complex pathophysiology. This study elucidates multiple beneficial mechanisms by which spironolactone addresses cognitive impairment associated with renal dysfunction. Spironolactone enhances BBB protection and restores BBB integrity which is often compromised with renal dysfunction. It promotes neuroplasticity (allowing for improved neural adaptation and cognitive function), additionally mediates cerebral blood flow (CBF) ensuring adequate oxygen and nutrient delivery to brain. Spironolactone's anti-inflammatory effects by inhibiting the nuclear factor-kappa B (NF-κB) pathway and modulation of neuregulin1 (NRG1)/v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 (ERBB4) signaling effectively reduce neuroinflammation that contributes to memory impairment. It also mitigates oxidative stress by targeting NADPH-oxidase (NOX), a major source of reactive oxygen species (ROS) in the central nervous system (CNS). Spironolactone also maintains hormonal balance, particularly regarding aldosterone levels, which become dysregulated in renal dysfunction and negatively impact brain function. These insights provide new possibilities for developing targeted therapies against renal dysfunction-induced memory impairment.

To address all the changes in the management of people with diabetes (DM) and chronic kidney disease (CKD), under the auspices of the Spanish Society of Nephrology (SEN), the Spanish Diabetic Nephropathy Study Group (GEENDIAB) decided to publish an updated Clinical Practice Guideline for detection and management of diabetic kidney disease (DKD). It is aimed at a wide audience of clinicians treating diabetes and CKD. The terminology of kidney disease in diabetic patients has evolved toward a more inclusive nomenclature that avoids underdiagnosis of this entity. Thus, the terms "diabetes and kidney disease" and "diabetic kidney disease" are those proposed in the latest KDIGO 2022 guidelines to designate the whole spectrum of patients who can benefit from a comprehensive therapeutic approach only differentiated according to eGFR range and albuminuria. Recommendations have been divided into five main areas of interest: Chapter 1: Screening and diagnosis of diabetic kidney disease, Chapter 2: Metabolic control in people with diabetes and CKD, Chapter 3: Blood pressure control in people with diabetic kidney disease, Chapter 4: Treatment targeting progression of CKD in people with diabetic kidney disease, and Chapter 5: Antiplatelet or anticoagulant therapy in people with diabetes and CKD. World Health Organization (WHO) recommendations for guideline development were followed to report this guideline. Systematic reviews were carried out, with outcome ratings and summaries of findings, and we reported the strength of recommendations following the "Grading of Recommendations Assessment, Development and Evaluation" GRADE evidence profiles.

Studies in patients with heart failure have indicated that sodium-glucose cotransporter 2 (SGLT2) inhibitors increase iron use and enhance erythropoiesis. In this post hoc analysis of the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we evaluated the effects of canagliflozin on iron metabolism in patients with chronic kidney disease (CKD) and whether the effects of canagliflozin on hemoglobin and cardiorenal outcomes were modified by iron deficiency.

We measured serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT) and ferritin at baseline and 12 months. The effects of canagliflozin, relative to placebo, on iron markers were assessed with analysis of covariance. Interactions between baseline iron deficiency, defined as TSAT <20%, and the effects of canagliflozin on hemoglobin and cardiorenal outcomes were evaluated with mixed effect models and Cox regression models, respectively.

Of 4401 participants randomized in CREDENCE, 2416 (54.9%) had iron markers measured at baseline, of whom 924 (38.2%) were iron deficient. Canagliflozin, compared with placebo, increased TIBC by 2.1% [95% confidence interval (CI) 0.4, 3.8; P = .014] and decreased ferritin by 11.5% (95% CI 7.1, 15.7; P < .001) with no clear effect on serum iron or TSAT. Canagliflozin increased hemoglobin over the trial duration by 7.3 g/L (95% CI 6.2, 8.5; P < .001) and 6.7 g/L (95% CI 5.2, 8.2; P < .001) in patients with and without iron deficiency, respectively (P for interaction = .38). The relative effect of canagliflozin on the primary outcome of doubling of serum creatinine, kidney failure or death due to cardiovascular disease or kidney failure (hazard ratio 0.70, 95% CI 0.56, 0.87) was consistent regardless of iron deficiency (P for interaction = .83), as were effects on other cardiovascular and mortality outcomes (all P for interactions ≥0.10).

Iron deficiency is highly prevalent in patients with type 2 diabetes and CKD. Canagliflozin increased TIBC and decreased ferritin in patients with type 2 diabetes and CKD, suggesting increased iron utilization, and improved hemoglobin levels and clinical outcomes regardless of iron deficiency.

This planned interim analysis of a mandatory post-marketing surveillance study in Japan evaluated the safety and effectiveness of roxadustat, the first approved hypoxia-inducible factor prolyl hydroxylase inhibitor in the world, in real-world clinical use.

This prospective observational study has a planned 104-week observation period. We report data obtained through 16 December 2023, as a planned interim analysis. Adverse drug reactions (ADRs), mean hemoglobin level change from baseline to 12 weeks of roxadustat treatment, and subgroup analyses stratified by either baseline C-reactive protein or albumin levels were reported.

Overall, 2084 patients were treated with roxadustat (total patient-years of exposure: 1579.2). In the non-dialysis-dependent (NDD) group (n = 1075), ADRs and serious ADRs occurred in 209 (19.4%) and 109 (10.1%) patients, respectively. In patients receiving hemodialysis (HD; n = 856), ADRs and serious ADRs occurred in 224 (26.2%) and 142 (16.6%) patients, respectively. In patients receiving peritoneal dialysis (PD; n = 146), ADRs and serious ADRs occurred in 46 (31.5%) and 26 (17.8%) patients, respectively. Mean hemoglobin levels reached target levels at 12 weeks in most patients (NDD: 54.6%; HD: 56.3%; PD: 45.4%).

Roxadustat safety was demonstrated in real-world clinical settings. No new safety concerns were identified.Trial Registration: NCT04408820.

Pre-transplantation red blood cell transfusion (RBCT) is a well-recognized cause of allosensitization. However, the effects of RBCT after kidney transplantation remain controversial. This study evaluates the impacts of RBCT within the first 30 days post-transplantation (early RBCT) with regard to long-term patient and graft outcomes. We retrospectively analyzed 785 patients who underwent HLA- and ABO-compatible kidney transplantation between 2014 and 2020. Patients were categorized based on whether they received early RBCT. Overall, 18.9% of patients received early RBCT. On multivariable analysis, early RBCT was independently associated with increased risks of all-cause mortality (hazard ratio, 2.264; 95% CI 1.186-4.324; P = 0.013) and death-censored graft loss (hazard ratio, 1.995; 95% CI 1.045-3.810; P = 0.036). Cumulative incidence of antibody-mediated rejection was significantly higher in the early RBCT group (P = 0.024). In the sensitivity analysis, the early RBCT significantly increased the risk of patient mortality (P = 0.017), death-censored graft loss (P = 0.018) and antibody-mediated rejection (P = 0.05), regardless of the donor profile. Early post-transplantation RBCT was associated with increased risks of all-cause mortality, graft loss, and antibody-mediated rejection, highlighting the need for reconsideration of transfusion practices following kidney transplantation.

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).

Anemia is a prevalent complication of chronic kidney disease (CKD) and is associated with increased mortality and reduced health-related quality of life. The iron-rich protein hemoglobin, which the body utilizes to carry oxygen, deteriorates in anemia. Because hemoglobin is a protein that contains iron, disturbances in iron homeostasis can lead to iron-deficiency anemia (IDA). CKD frequently results in anemia, which is linked to a poor prognosis. Nevertheless, whether anemia per se or other comorbidities are the reason for this connection remains unclear. Uncertainty surrounds whether distinct forms of IDA can forecast CKD outcomes. Physicians, nurse practitioners, physician assistants, and registered nurses work as a team to manage anemia in patients with CKD. Individuals with CKD can benefit from the involvement of different specialties along the treatment continuum, and dietitians/nutritionists can play a significant role in enhancing management through multidisciplinary care. This literature review aims to deliver a comprehensive overview of IDA in CKD, concentrating on its diagnosis. It addresses the pathophysiology, complications associated with iron deficiency, and the available diagnostic tests for IDA in CKD. Furthermore, we analyze the literature that has contributed to developing current practice guidelines for treating IDA in CKD and encouraging multidisciplinary team collaboration in managing IDA in CKD.

Chronic kidney disease (CKD) is a complex medical condition that extends beyond the progressive decline in renal function. It is associated with mineral and bone disorders, notably secondary hyperparathyroidism due to dysregulated calcium and phosphate metabolism. However, distinguishing between secondary and primary hyperparathyroidism can be challenging. We report the case of a 74-year-old male with CKD, who presented with elevated serum levels of parathyroid hormone (PTH), CKD, and unexplained hypercalcemia, despite management for secondary hyperparathyroidism. Advanced imaging techniques revealed a primary parathyroid adenoma, subsequently confirmed by histopathology. The successful surgical resection of the adenoma resulted in the calcium and PTH levels falling into a normal range, highlighting the need for a careful differential diagnosis in CKD patients.

Background/Objectives: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved to treat anemia of chronic kidney disease (CKD). The efficacy and safety of roxadustat compared with parenteral erythropoiesis-stimulating agents (ESAs) were evaluated in patients with anemia of CKD receiving peritoneal dialysis (PD). Methods: This analysis pooled data from four phase 3, multicenter, randomized, open-label, active-comparator studies (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES). The primary endpoints evaluated were hemoglobin change from baseline (CFB) to Weeks 28-36 without rescue therapy and hemoglobin CFB to Weeks 28-52 regardless of rescue therapy use. Safety data were reported. Results: This analysis included 422 patients (215 roxadustat, 207 ESA). Hemoglobin CFB to Weeks 28-36 without rescue therapy and hemoglobin CFB to Weeks 28-52 regardless of rescue therapy achieved non-inferiority for roxadustat vs. ESAs. The mean weekly dose of roxadustat was maintained over time (Weeks 1-4, 3.86 mg/kg/week; Weeks 101-104, 3.27 mg/kg/week), whereas the mean weekly ESA dose increased by 24% (Weeks 1-4, 115.70 IU/kg/week; Weeks 101-104, 143.40 IU/kg/week). Fewer patients treated with roxadustat received intravenous iron supplementation and rescue therapy, and patients treated with an ESA required blood transfusions sooner. Roxadustat-treated patients experienced a greater decrease in low-density lipoprotein cholesterol levels relative to baseline vs. ESA-treated patients. Treatment-emergent adverse events were similar in both treatment groups. Major adverse cardiovascular event (MACE), MACE plus unstable angina or congestive heart failure, and all-cause mortality hazard ratios were <1; the lower limit of the 95% CIs was <0.6, and the upper limit was >1.3. Conclusions: Roxadustat was non-inferior to ESAs in correcting and maintaining hemoglobin levels, with stable dosing and a comparable safety profile, in anemic patients receiving PD.

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.

Cardiovascular diseases are common complications in chronic kidney disease (CKD). Oxidative stress associated with renal and metabolic dysfunctions is one of the cardiovascular complications (CVC) in haemodialysis patients. The aim of the present study is to analyse the oxidative stress markers in CDK patients supplemented with antioxidants and vitamin E, with monitoring of CVC.

This was a cross-sectional study conducted on 99 subjects. CKD patients received oral supplementation of vitamin E (300 mg/day) for 2 years. Oxidative stress markers, nitric oxide (NO); myeloperoxidase (MPO); oxidized low-density lipoprotein (LDLox); malondialdehyde (MDA) and glutathione were measured before and after the vitamin treatment.

NO (62.62 ±2.80 μmol/l), LDLox (10.55 ±4.62 μmol/l), MDA (6.11 ±2.83 μmol/l) and MPO (53.35 ±3.82 UI/ml) were overconcentrated, while glutathione (62.09 ±4.15 UI/ml) was less concentrated in CKD patients with cardiovascular complications, compared to those without cardiovascular complications (67.08 ±1.90 μmol/l, 31.18 ±5.25 μmol/l, 16 ±6.47 μmol/l, 57.00 ±7.24 UI/ml, 43.09 ±3.33 UI/ml, respectively). After 2 years of vitamin E treatment, the overall cardiovascular complications were not significantly decreased.

These results showed that oral complementation with vitamin E did not affect the occurrence of cardiovascular complications associated with CKD. These findings may pave the way for future innovative strategies for antioxidant supplementation in CKD patients.

Background/Objectives: Phosphate is a macro-element involved in all cellular energetic processes. As about 90% of the phosphate filtered by the glomerulus is excreted by kidneys, the impairment of renal function and the consequent over-secretion of parathyroid hormone and fibroblast growth factor 23 results in the increase in the serum phosphate levels. The association between phosphate and hemoglobin is controversial, as both direct and indirect relationships have been reported. The present study aims to investigate the relationship between phosphate and hemoglobin in a large prospective, longitudinal cohort including dialysis patients from the Sicilian Registry of Nephrology, Dialysis, and Transplantation. Methods: In this prospective cohort study, we included 6263 hemodialysis patients to achieve a total of 120,462 repeated measurements of serum phosphate and hemoglobin over time. The longitudinal association between phosphate and hemoglobin was analyzed by univariate and multivariate Linear Mixed Models. Results: The mean age was 66 ± 16 years and the median dialysis vintage was 5 months [IQR: 2-16]. Mean and median values of hemoglobin and phosphate were 10.7 g/dL (SD 1.3 g/dL) and 4.6 mg/dL [IQR 3.9-5.5 mg/dL], respectively. The multivariate model, adjusted for potential confounders, confirmed the positive association between serum phosphate and hemoglobin [adjβ = 0.13, 95%CI 0.03-0.23, p = 0.01)]. These results were confirmed in analyses stratified for the use of phosphate binders. Conclusions: In our large cohort of dialysis patients, we found a linear, direct relationship between phosphate and hemoglobin levels. As a reduction in phosphate is associated with a parallel reduction in hemoglobin levels, hypophosphatemia can accentuate anemia in dialysis patients. Our results generate the hypothesis that monitoring serum phosphate in clinical practice might provide a better management of anemia.

The aim of this study was to investigate iron status and iron deficiency in incident continuous ambulatory peritoneal dialysis (CAPD) patients and identify influencing factors.

Patients with end-stage renal disease were enrolled. Clinical data of iron metabolism and biochemical and dialysis parameters during the first peritoneal dialysis evaluation were collected. Serum ferritin (SF) and transferrin saturation (TSAT) levels were evaluated, and independent influencing factors were identified by correlation and regression analyses.

Of 1,128 adult CAPD patients, 41.2% had iron deficiency (ID), 15.7% had absolute iron deficiency, and 8.2% had functional iron deficiency. The average SF level was (276.8 ± 277.9) μg/L, and iron saturation was (29.8 ± 12.7)%. Additionally, 50.2 and 69.3% of patients reached targets in SF level and iron saturation recommended by the Chinese Society of Nephrology. SF level and TSAT were not correlated with estimated glomerular filtration rate, whereas negatively correlated with platelet count and inflammatory factors. Low platelet count, presence of diabetes mellitus and high interleukin 6 levels were independent factors of lower TSAT.

ID is common in patients with CAPD. Women and those with thrombocytopenia, diabetes, and inflammation are at higher risk for iron storage or reduced iron utilization. In the initial CAPD stage, a reasonable iron supplement strategy may be established for CAPD patients with high-risk factors.

Purpose: While intravenous (IV) iron repletion is an effective tool to treat anemia and improve outcomes in chronic kidney disease (CKD), guideline laboratory definitions of iron deficiency differ, resulting in variability in screening and repletion strategies. This study sought to describe current practices surrounding identification and treatment of iron deficiency in CKD and then implement a pharmacist-led protocol to optimize care at a tertiary medical center. Methods: This single center, retrospective, pre- and post-protocol implementation study of adults with CKD admitted to the inpatient setting first analyzed historic practices for iron deficiency screening and treatment, followed by deployment of a pharmacist-driven protocol for iron deficiency screening and treatment. Iron deficiency was defined as transferrin saturation of ≤30% and ferritin of ≤500 ng/mL. Improvement in screening and repletion rates was analyzed. Results: Historic pre-protocol practices were reviewed in 7155 admissions of which 2559 (35.8%) included screening for iron deficiency. Over the 2 months intervention (post-protocol) period, 315 admissions were included. The average age of patients in the post-protocol cohort was 64.1 years, 53.7% were female, and 26.4% were dialysis dependent. Compared to pre-protocol, patients were 2.33 (95% CI 2.20-2.47) times more likely to be screened and deficient patients were 2.05 (95% CI 1.46-2.86) times more likely to be treated, with most receiving IV iron therapy (85.4%), in the post-protocol cohort. Patients were 3.58 times (95% CI 1.97-6.48) more likely to receive IV iron versus oral alone in the post-protocol cohort compared to pre-protocol. Conclusion: The frequency of patients with CKD screened and treated with iron increased after implementation of a pharmacist-driven protocol. This study underscores the need for a systematic approach to identification/treatment of iron deficiency in this population.

Several treatment options are available for anemia associated with chronic kidney disease (CKD); however, there remains a lack of awareness of physician and patient preferences regarding these treatments. We aimed to explore physicians' and patients' perceptions and preferences regarding the management of anemia of CKD in Japan.

A web-based survey, including best-worst scaling (BWS), was conducted with physicians who had treated ≥1 patient with anemia of CKD in the preceding year, and with patients with CKD who self-reported a clinical diagnosis of anemia of CKD or low hemoglobin levels. A three-step approach was used comprising cognitive interviews, a pilot survey, and a main survey. The BWS survey results were analyzed using multinomial logit and hierarchical Bayesian models.

The survey was completed by 906 participants: 103 patients (average age 60.6 years; 77.7% male) and 803 physicians (166 nephrologists, 214 cardiologists, 137 diabetologists, and 286 general internists). Almost all (96.0%) physicians surveyed considered anemia of CKD to be an important condition to treat. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors had the highest treatment satisfaction among physicians, whereas patients had the highest satisfaction with both erythropoietin-stimulating agent therapy and HIF-PH inhibitors. Approximately one-third (35.9%) of patients surveyed indicated that they were receiving treatment. When comparing the relative importance of attributes and levels, physicians favored efficacy (particularly improvement in hemoglobin levels), whereas patients favored safety (particularly a lower rate of severe adverse events).

Although a majority of physicians consider treatment of CKD-related anemia important, differences in the perceptions and usage of medications exist between medical specialties. Preferences for the management of anemia of CKD vary between physicians and patients; therefore, patient involvement in treatment decisions may help optimize outcomes.

Chronic kidney disease (CKD) is a progressive and incurable condition that imposes a significant burden on an aging society. Although the exact prevalence of this disease is unknown, it is estimated to affect at least 800 million people worldwide. Patients with diabetes or hypertension are at a higher risk of developing chronic kidney damage. As the kidneys play a crucial role in vital physiological processes, damage to these organs can disrupt the balance of water and electrolytes, regulation of blood pressure, elimination of toxins, and metabolism of vitamin D. Early diagnosis is paramount to prevent potential complications. Treatment options such as dietary modifications and medications can help slow disease progression. In our narrative review, we have summarized the available therapeutic options to slow the progression of chronic kidney disease. Many new drug treatments have recently become available, offering a beacon of hope and optimism in CKD management. Nonetheless, disease prevention remains the most critical step in disease management. Given the significant impact of CKD on public health, there is a pressing need for further research. With the development of new technologies and advancements in medical knowledge, we hope to find more effective diagnostic tools and treatments for CKD patients.

Molidustat is a novel agent investigated for the treatment of anemia in both dialysisdependent (DD) and non-dialysis-dependent (NDD) patients. Its efficacy and safety are still unclear.

We searched five databases to identify randomized controlled trials comparing molidustat to erythropoiesis-stimulating agents (ESAs) or placebo in patients with anemia.

Six studies containing 2025 eligible participants were identified. For NDD patients, the change in Hb levels from baseline (ΔHb) was significantly higher for molidustat than for placebo [mean difference (MD) = 1.47 (95 % CI: 1.18 to 1.75), P < 0.00001] and ΔHb was also significantly higher for molidustat than for ESAs [MD = 0.25 (95 % CI 0.09 to 0.40), P = 0.002]. For NDD patients, Δhepcidin was significantly lower for molidustat than for placebo [MD = -20.66 (95 % CI: -31.67 to -9.66), P = 0.0002] and Δhepcidin was also significantly lower for molidustat than for ESAs [MD = -24.51 (95 % CI: -29.12 to -19.90), P < 0.00001]. For NDD patients, Δiron was significantly lower for molidustat than for ESAs [MD = -11.85 (95 % CI: -15.52 to -8.18), P < 0.00001], and ΔTSAT was also significantly lower for molidustat than for ESAs [MD = -5.29 (95 % CI: -6.81 to -3.78), P < 0.00001]. For NDD patients, Δferritin was significantly lower for molidustat than for placebo [MD = -90.01 (95 % CI: -134.77 to -45.25), P < 0.00001]. However, for DD-CKD patients, molidustat showed an effect similar to that of ESAs on increasing the Hb level [MD = -0.18 (95 % CI: -0.47 to 0.11), P = 0.23], Δiron level [MD = 3.78 (95 % CI: -7.21 to 14.76), P = 0.5], Δferritin level [MD = 25.03 (95 % CI: -34.69 to 84.75), P = 0.41], and Δhepcidin level [MD = 1.20 (95 % CI: -4.36 to 6.76), P = 0.67]. For DD-CKD patients, compared with the placebo or ESA group, molidustat showed a significantly higher level on ΔTSAT[MD = 3.88 (95 % CI: 2.10 to 5.65), P < 0.0001] and a slightly increased level on ΔTIBC level [MD = 1.08 (95 % CI: -0.07 to 2.23), P = 0.07]. There was no significant difference in the incidence of severe adverse events (SAEs), death, and cardio-related adverse events between molidustat and the ESAs groups.

Moricizine can effectively improves Hb levels in NDD patients and corrects anemia in DD patients without increasing adverse event incidence.

Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD).

In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [Tsat] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks.

A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: -0.76; 95% confidence interval [CI]: -1.291 to - 0.2383). The improvement in Hb was higher in women than in men (P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone (P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate (P = 0.14) and a non-significant increase in C-reactive protein (P = 0.54) level.

Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.

Iron metabolism disorders and anemia are one of the main complications of end-stage renal disease that may affect the evaluation process for kidney transplantation. The study aimed to assess the iron metabolism in hemodialysis patients in relation to waiting list status.

The study included 5068 hemodialysis patients, including those on the active waiting list (N = 449) and those who were not eligible for the waitlist (N = 4619). Demographic and biochemical data, Charlson's comorbidity index, duration of hemodialysis therapy and, respectively, hemoglobin, ferritin, and transferrin saturation levels were compared in both groups of patients.

Patients on the active waiting list were significantly younger -53.2 vs 67.2 years (P < .001), with a lower Charlson comorbidity index score: 3.33 vs 4.42 (P < .001). The duration of hemodialysis therapy was similar: 66.0 vs 63.2 months (P = .416), the incidence of anemia according to World Health Organization (90.6%, vs 91.2%) and KDIGO (72.4% vs 70.4%). The degree of anemia correction in terms of hemoglobin concentration and transferrin saturation was comparable in both groups and amounted to an average of 10.9 g/dL (P = .349) for hemoglobin concentration and 32.7% vs 33.4% (P = .513) for transferrin saturation. However, there was a statistically significant difference in ferritin concentration: 554 ug/L vs 733 ug/L (P = .001).

Patients on the active list have significantly lower ferritin levels despite similar duration of hemodialysis treatment and comparable hemoglobin values. This may be due to lower inflammation, and less frequent blood transfusions, and lead to a lower risk of immunization and an increased chance of potential kidney transplantation.

To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD).

Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis.

Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes.

A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.

The Anemia Control Model (ACM) is a certified medical device suggesting the optimal ESA and iron dosage for patients on hemodialysis. We sought to assess the effectiveness and safety of ACM in a large cohort of hemodialysis patients.

This is a retrospective study of dialysis patients treated in NephroCare centers between June 1, 2013 and December 31, 2019. We compared patients treated according to ACM suggestions and patients treated in clinics where ACM was not activated. We stratified patients belonging to the reference group by historical target achievement rates in their referral centers (tier 1: <70%; tier 2: 70-80%; tier 3: >80%). Groups were matched by propensity score.

After matching, we obtained four groups with 85,512 patient-months each. ACM had 18% higher target achievement rate, 63% smaller inappropriate ESA administration rate, and 59% smaller severe anemia risk compared to Tier 1 centers (all p < 0.01). The corresponding risk ratios for ACM compared to Tier 2 centers were 1.08 (95% CI: 1.08-1.09), 0.49 (95% CI: 0.47-0.51), and 0.64 (95% CI: 0.61-0.68); for ACM compared to Tier 3 centers, 1.01 (95% CI: 1.01-1.02), 0.66 (95% CI: 0.63-0.69), and 0.94 (95% CI: 0.88-1.00), respectively. ACM was associated with statistically significant reductions in ESA dose administration.

ACM was associated with increased hemoglobin target achievement rate, decreased inappropriate ESA usage and a decreased incidence of severe anemia among patients treated according to ACM suggestion.

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.

Erythropoiesis-stimulating agents (ESAs) have been a common treatment for anemia associated with chronic kidney disease (CKD), while 10-20 % of patients continue to suffer from persistent anemia despite receiving ESA treatments. Our previous findings suggested that intensive ESA usage can cause resistance by depleting the erythroid precursor cells. Here, we used a mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model of ESAs and conducted simulations to evaluate the influence of dose regimens and other factors (such as administration route, individual PK/PD parameters, types of ESAs, and disease status) on ESA resistance with instantaneous dose adaptations in healthy populations and anemic patients. The simulated results show that instantaneous dose-adaptation can reduce ESA resistance, but up to 30 % of subjects still ended up developing ESA resistance in healthy populations. The Smax is markedly higher in hypo-responders than in normal-responders, while hypo-responders possess fewer precursors and experience a faster decline compared to normal-responders. There is a ceiling effect of increasing ESA dosage to improve HGB responses and reduce ESA resistance, and the limit is lower in anemic patients compared to healthy populations. Subcutaneous administrations and ESAs with longer half-lives lead to stronger HGB responses and less resistance at equivalent doses. Taken together, this study indicates that precursor depletion contributes to ESA resistance and dose regimens can greatly influence the occurrence of ESA resistance. Furthermore, ESA treatment for patients showing ESA resistance should avoid continuously increasing doses and instead consider stimulating the renewal of precursors.

Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs).

This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60-100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency.

Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, - 20.09 ng/mL; 95% CI, - 30.26 to - 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, - 7.87 nmol/L; 95% CI, - 12.11 to - 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study.

Compared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients.

This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231).

The global prevalence of chronic kidney disease (CKD) in the general population is relatively clear. Our previous study showed that elderly individuals who are physically disabled are more likely to experience kidney function impairment, and the main purpose of this study was to determine the prevalence and risk factors associated with CKD in elderly patients with physical disabilities.

A total of 2679 elderly individuals with physical disabilities from the 2018 Shanghai Disability Health Survey were screened to calculate the prevalence of CKD. Multiple logistic regression was performed to identify the factors associated with CKD. Detailed subgroup analyses of disability level were also conducted.

We confirmed CKD in 287 of 2679 (10.7%) participants. Female sex, age, history of hypertension, red blood cell count, albumin, urea, and uric acid (UA) were independently correlated with CKD. Age and UA abnormalities were common risk factors for different levels of disabilities.

The prevalence of CKD is higher in the mild level of older physically handicapped individuals. Age and the level of UA should also be considered in this population. The preventive strategies for patients with two levels of elderly disability should have different focuses.

The function of the kidney is tightly linked to the function of the heart. Dysfunction/disease of the kidney may initiate, accentuate, or precipitate of the cardiac dysfunction/disease and vice versa, contributing to a negative spiral. Further, the reciprocal association between the heart and the kidney may occur on top of other entities, usually diabetes, hypertension, and atherosclerosis, simultaneously affecting the two organs. Chronic kidney disease (CKD) can influence cardiac function through altered hemodynamics and salt and water retention, leading to venous congestion and therefore, not surprisingly, to heart failure (HF). Management of HF in CKD is challenging due to several factors, including complex interplays between these two conditions, the effect of kidney dysfunction on the metabolism of HF medications, the effect of HF medications on kidney function, and the high risk for anemia and hyperkalemia. As a result, in most HF trials, patients with severe renal impairment (i.e., eGFR 30 mL/min/1.73 m2 or less) are excluded. The present review discusses the epidemiology, pathophysiology, and current medical management in patients with HF developing in the context of CKD.

Renal anemia, a common complication and threat factor of chronic kidney disease (CKD), has long been treated with injectable erythropoietin-stimulating agents (ESAs). As concerns regarding cardiovascular safety and erythropoietin resistance to ESAs have emerged, alternative therapies are urgently needed. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an oral agent, has been proven to be effective in improving renal anemia. However, the effects of HIF-PHIs on nondialysis-dependent CKD (NDD-CKD) have yet to be supported by updated meta-analyses.

A meta-analysis of clinical randomized controlled trials (RCTs) on HIF-PHI treatment of NDD-CKD patients based on PubMed, EMBASE, and Cochrane databases as of July 16th, 2023, was conducted. The primary outcomes were the level of hemoglobin (Hb) postintervention and the ratio of Hb responses. Most of the analysis was conducted via RevMan 5.3 software using a random-effects model. Stata (version 15.0) was used to analyze the publication bias.

Twenty-two studies with a total of 7178 subjects in the HIF-PHI group, 3501 subjects in the ESA group and 2533 subjects in the placebo group were enrolled. HIF-PHIs increased the level of Hb and improved iron metabolism but were not inferior to ESAs in terms of safety.

HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia.

Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.

Chronic kidney disease (CKD) is classified into five stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called 'uremic toxins', and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure, occurs early in CKD and reaches a prevalence of 70-80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter-2 inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored.