Erythropoiesis-stimulating Agents Dose Research Articles

Anemia: A Connection Between Heart Failure and Kidney Failure

Erythropoiesis-stimulating agents (ESAs) have improved the quality of life and reduced the need for transfusions in patients with chronic kidney disease. However, randomized trials showed no benefit but possible safety issues following high doses of ESAs given to reach normal hemoglobin levels. Iron therapy is used together with ESA; when given proactively, it may reduce the risk of mortality and cardiovascular events in hemodialysis patients. Recent trials also showed benefits of intravenous iron therapy in patients with heart failure. New drugs for correcting anemia may retain the present efficacy of ESAs as antianemic drugs and reduce cardiovascular risks.

A possible contributor to erythropoiesis-stimulating agents requirement in hemodialysis: Paraoxonase 1 activity

Background: Anemia is one of the most prevalent complications of chronic kidney disease (CKD). In CKD-related anemia, circulating erythrocytes have a decreased life span. Paraoxonase-1 (PON1) activity is one of the essential factors protecting cell membranes, e.g., erythrocytes, from lipid peroxidation under normal conditions. In this study, we investigated PON1 activity in hemodialysis (HD) patients with and without erythropoiesis-stimulating agents (ESA) therapy and the possible relationship of PON1 activity levels with the ESA dose required.
 Methods: This study is composed of patients undergoing HD with a minimum dialysis vintage of six months. We excluded cases with an active infection, cardiovascular events and malignancy, hypo- or hyperthyroidism, central venous catheters, iron deficiency, cystic kidney diseases, nephrectomy, and routine C-reactive protein (CRP) levels higher than reference range within the last six months.
 Results: Baseline characteristics, laboratory parameters, oxidative stress, and systemic inflammatory indices were similar between groups. The mean PON1 activity of the ESA+ group was significantly lower than the ESA– group (191.4 ±118.8 and 488.1±174.9,respectively; p

Institutional Usage of Ferric Pyrophosphate Citrate (FPC) Delivered Via Dialysate in Reducing Erythropoiesis Stimulating Agents (ESAs) and IV Iron Cost.

Dialysis patients are often iron deficient due to a multiple factors. Ferric pyrophosphate citrate is a complex iron salt that can be given via dialysate allowing maintenance of hemoglobin (Hgb) concentration and iron balance while reducing the need for IV iron. The purpose of this study is to perform a cost evaluation of FPC and the effect it has on lowering the dose/use of ESAs and IV iron therapy. This study reviewed the same 100 hemodialysis patient's charts before and after the use of FPC. The data points that were collected and analyzed are as follows: hemoglobin, ferritin levels, average weekly ESA dosing, and IV iron replacement therapy dose. Out of 100 patients, there was no statistical difference in the average hemoglobin, ferritin, and iron saturation levels observed in the patients before and after FPC use. The average weekly dose of darbepoetin alfa per patient was 52.74 μg before the FPC group compared to 39.27 μg in the post FPC group (P < .0001). The total dose of ferric gluconate per patient was 3290.01 mg in the before FPC group and 585.60 mg in the post FPC group (P < .0001). The average total iron sucrose dose per patient in the before FPC group was 3097.92 mg versus 1216.67 mg in the post FPC group (P < .1563). When comparing FPC's cost and implementation into both of our outpatient dialysis centers, this yielded a net savings of $296 751.49.

Long-term efficacy and safety of iron-based phosphate binders, ferric citrate hydrate and sucroferric oxyhydroxide, in hemodialysis patients.

Iron-based phosphate binders, including ferric citrate hydrate (FCH) and sucroferric oxyhydroxide (SFOH), have been used for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. However, the long-term efficacy and safety of these agents have not yet been clearly elucidated. Laboratory data of 56 hemodialysis patients who had been prescribed either FCH (n = 33) or SFOH (n = 23) were retrospectively examined. We showed that both FCH and SFOH significantly and consistently decreased serum phosphate concentrations in the patients undergoing maintenance hemodialysis during the 36-month observation period. Serum levels of calcium, intact parathyroid hormone, as well as hemoglobin levels were unaltered. No overshoot of parameters of iron metabolism, such as transferrin saturation and serum ferritin levels, was observed, and serum ferritin level remained under 300ng/mL in most patients. A trend towards decrease in the doses of erythropoiesis-stimulating agents used and frequency of intravenous iron use was observed in both treatment groups. No severe adverse drug reactions were observed in either the patients receiving FCH or SFOH. The results of the present study suggest that the iron-based phosphate binders, FCH and SFOH, decrease serum phosphate concentrations consistently and are safe to use over the long-term in maintenance hemodialysis patients.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients

Background: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. Methods: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011–2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. Results: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). Conclusions: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Effect of increased blood flow rate on renal anemia and hepcidin concentration in hemodialysis patients

BackgroundIncreasing the blood flow rate (BFR) is a useful method for increasing Kt/V and the clearance for low molecular solutes. Hemodialysis patients are often anemic due to hypoerythropoiesis and their chronic inflammatory state. Hepcidin, a hormone that regulates iron homeostasis, is considered as an indicator of iron deficiency in patients with end-stage renal disease. This study aimed to investigate the effects of an increased BFR during hemodialysis on serum hepcidin levels and anemia.MethodsBetween April 2014 and March 2016, 22 chronic dialysis patients (11 men [50.0 %]; mean [± standard deviation] age, 72 ± 12 years) undergoing maintenance hemodialysis treatment, thrice weekly, were enrolled and followed prospectively for 24 months. In April 2014, the BFR was 200 mL/min; in April 2015 this was increased to 400 mL/min, which was within acceptable limits. The dialysate flow rate remained stable at; 500mlL/min. Blood samples were collected in March 2015 and 2016. The primary endpoint was the comparison of the amounts of erythropoiesis-stimulating agent (ESA) required.ResultsThe increased BFR increased the Kt/V and contributed to significantly decreased urea nitrogen (UN) (p = 0.015) and creatinine (Cr) (p = 0.005) levels. The dialysis efficiency was improved by increasing the BFR. Ferritin (p = 0.038), hepcidin (p = 0.041) and high-sensitivity interleukin-6 (p = 0.038) levels were also significantly reduced. The ESA administered was significantly reduced (p = 0.004) and the Erythropoietin Resistant Index (ERI) significantly improved (p = 0.031). The reduction rates in UN (p < 0.001), Cr (p < 0.001), and beta-2 microglobulin (p = 0.017) levels were significantly greater post the BFR increase compared to those prior to the BFR increase. However, hepcidin was not affected by the BFR change.ConclusionsIncreasing BFR was associated with hemodialysis efficiency, and led to reduce inflammatory cytokine interleukin-6, but did not contribute to reduce C-reactive protein. This reduced hepcidin levels, ESA dosage and ERI. Hepcidin levels were significantly correlated with ferritin levels, and it remains to be seen whether reducing hepcidin leads to improve ESA and iron availability during anemia management.

Pleiotropic effect of erythropoiesis-stimulating agents on circulating endothelial progenitor cells in dialysis patients

Recent studies have suggested that erythropoiesis-stimulating agents (ESAs) may accelerate not only angiogenesis but also vasculogenesis, beyond erythropoiesis. We conducted a 12-week prospective study in 51 dialysis patients; 13 were treated with recombinant human erythropoietin (EPO, 5290.4 ± 586.9IU/week), 16 with darbepoetin (DA, 42.9 ± 4.3µg/week), 12 with epoetin β pegol (CERA, 40.5 ± 4.1µg/week) and 10 with no ESAs. Vascular mediators comprising endothelial progenitor cells (EPCs), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and high-sensitivity C-reactive protein (hs-CRP) were measured at 0 and 12weeks. EPCs were measured by flow cytometry as CD45lowCD34+CD133+ cells. The EPC count increased significantly to a greater extent in the EPO group than in the other three group, and increased significantly from 0 to 12weeks in a EPO dose-dependent manner. In both the DA and CERA groups, the EPC count did not change at 12weeks. Serum levels of VEGF, MMP-2 and hs-CRP were not affected by ESA treatment in all groups. In the CERA group, serum ferritin decreased significantly compared to the no-ESA group and correlated with CERA dose, although use of iron was permitted if required during the prospective study period of 12weeks. When patients on dialysis were treated with clinical doses of various ESAs, only EPO induced a significant increase of circulating EPCs from bone marrow, whereas, DA and CERA had no effect.

Ferric carboxymaltose vs. ferrous sulfate for the treatment of anemia in advanced chronic kidney disease: an observational retrospective study and cost analysis

In non-dialysis-dependent chronic kidney disease (NDD-CKD), erythropoiesis-stimulating agents (ESAs) and iron supplementation are essential for anemia management. Ferric carboxymaltose (FCM) is a relatively novel intravenous iron formulation used in different clinical settings, although scarce data exist in NDD-CKD patients. Primary objective of this study was to retrospectively evaluate the efficacy of FCM compared with oral ferrous sulfate for the treatment of iron-deficiency anemia in a cohort of NDD-CKD patients, considering also the treatment costs. This was a monocentric, retrospective observational study reviewing 349 NDD-CKD patients attending an outpatient clinic between June 2013 and December 2016. Patients were treated by either FCM intravenous infusion or oral ferrous sulfate. We collected serum values of hemoglobin, ferritin and transferrin saturation (TSAT) and ESAs doses at 12 and 18 months. The costs related to both treatments were also analysed. 239 patients were treated with FCM intravenous infusion and 110 patients with oral ferrous sulfate. The two groups were not statistically different for age, BMI and eGFR values. At 18 months, hemoglobin, serum ferritin and TSAT values increased significantly from baseline in the FCM group, compared with the ferrous sulfate group. ESAs dose and rate of infusion decreased only in the FCM group. At 18 months, the treatment costs, analysed per week, was higher in the ferrous sulfate group, compared with the FCM group, and this was mostly due to a reduction in ESAs prescription in the FCM group. Routine intravenous FCM treatment in an outpatient clinic of NDD-CKD patients results in better correction of iron-deficiency anemia when compared to ferrous sulfate. In addition to this, treating NDD-CKD patients with FCM leads to a significant reduction of the treatment costs by reducing ESAs use.

POS-281 Prognostic Significance of Erythropoiesis-Stimulating Agent Dose Requirements in PIVOTAL and its Implications for the Potential Mechanisms of IV Iron Benefit in Maintenance Haemodialysis Patients

POS-281 Prognostic Significance of Erythropoiesis-Stimulating Agent Dose Requirements in PIVOTAL and its Implications for the Potential Mechanisms of IV Iron Benefit in Maintenance Haemodialysis Patients

Erythropoietin Resistance Index and the Affecting Factors in Children with Peritoneal Dialysis

Background: Erythropoiesis-stimulating agents (ESAs) are used to treat anemia in CKD. Erythropoietin resistance index (ERI) is a useful tool used to evaluate the response to ESAs. In this study, we aimed to evaluate the causes of high ERI in children undergoing peritoneal dialysis (PD). Method: Patients who had been on PD for at least 1 year were included in this retrospective study. Demographic characteristics, residual kidney function (RKF), adequacy of dialysis, peritoneal glucose exposure, the number and reason for hospitalization, and medications were recorded. Anemia and laboratory parameters that may affect anemia were noted by taking the average of laboratory values in the last follow-up year (time-averaged). The weekly ESA dose was proportioned to the annual average hemoglobin value and body weight to calculate the ERI in terms of U/kg/week/g/dL. Results: A total of 100 patients were included in the study. The mean ESA dose and ERI value were 119.8 ± 66.22 U/kg/week and 13.01 ± 7.52 U/kg/week/g/dL, respectively. It was determined that the patients <5 years of age have very high ERI value, and these patients need 2 times more ESA than those >10 years of age. Absence of RKF, large number of hospitalization, and ACEI use were also found to affect the ERI value negatively. Conclusion: We demonstrate that the most important factor affecting ERI value is young age. We also reveal that absence of RKF, large number of hospitalization, and ACEI use are also important variables affecting the ERI value.

Hyporesponsiveness to long-acting erythropoiesis-stimulating agent is related to the risk of cardiovascular disease and death in Japanese patients on chronic hemodialysis: observational cohort study

BackgroundResponsiveness to erythropoiesis-stimulating agents (ESAs) is thought to be related to prognosis in patients on hemodialysis. A multi-center, prospective cohort study was conducted to investigate the effects of hyporesponsiveness to long-acting ESAs on cardiovascular events and mortality in Japanese patients on chronic hemodialysis.MethodsA total of 127 chronic hemodialysis patients treated with long-acting ESAs were followed-up prospectively. Responsiveness to ESA was evaluated using an erythropoietin resistance index (ERI) calculated by dividing the weekly body-weight-adjusted ESA dose by the hemoglobin concentration. The primary endpoint of this survey was defined as a combination of cardiovascular events and all-cause deaths. The association between hyporesponsiveness to ESAs evaluated by the highest quartile of the ERI and the primary endpoint was investigated.ResultsDuring the follow-up period (median 4.6 years), 32 patients reached the primary end point. Kaplan-Meier curve analysis showed that patients with ESA hyporesponsiveness belonging to the highest quartile of the ERI reached the primary end point more frequently than those without (P = 0.031). Cox regression analysis showed that an ERI in the highest quartile was an independent predictor of the primary end point, even after adjustment using a propensity score (hazard ratio 2.76, 95% confidence interval 1.19–6.40).ConclusionsESA hyporesponsiveness in hemodialysis patients treated with long-acting ESAs is related to cardiovascular events and death.

Effect of L-carnitine supplementation on renal anemia in patients on hemodialysis: a meta-analysis.

L-carnitine is an amino acid derivative that is thought to be helpful for treating renal anemia in hemodialysis patients. However, the mechanism remains to be fully elucidated. A literature search was performed on PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) and conduct a meta-analysis for investigating the effect of L-carnitine in the treatment of renal anemia in participants receiving hemodialysis. A total of 18 eligible trials with 1090 participants were included in this study. L-carnitine can significantly increase plasma free L-carnitine levels (mean difference [MD]: 140.53, 95% confidence interval [CI] 102.22-178.85; P < 0.00001), decrease the erythropoietin responsiveness index (ERI; MD: -2.72, 95% CI -3.20 to -2.24; P < 0.00001) and the required erythropoiesis-stimulating agent (ESA) doses (MD: -1.70, 95% CI -2.04 to -1.36; P < 0.00001). However, the use of L-carnitine was not associated with a higher hemoglobin level (MD: 0.18, 95% CI -0.20 to 0.55; P = 0.35) and hematocrit level (MD: 1.07, 95% CI -0.73 to 2.87; P = 0.24). In subgroup analyses, the effects of L-carnitine supplementation on renal anemia in patients on hemodialysis were independent of the treatment duration and intervention routes. The present meta-analysis indicated that L-carnitine therapy significantly increased plasma L-carnitine concentrations, improved the response to ESA, decreased the required ESA doses in patients receiving hemodialysis, and maintained hemoglobin and hematocrit levels. L-carnitine supplementation should be supported in hemodialysis patients. However, the relationship between L-carnitine treatment and long-term outcomes is still unclear. Further high-quality RCTs are needed to verify our findings.

Expanded Hemodialysis and Its Effects on Hospitalizations and Medication Usage: A Cohort Study

Introduction: Expanded hemodialysis (HDx) effectively removes large middle molecular uremic toxins (>25 kDa) while still retaining albumin, potentially reducing their adverse effects. We compare the clinical laboratory parameters, hospitalization rates, and medication use in a cohort of patients switched from high-flux HD to HDx. Methods: This is a multicenter, observational cohort study of 81 adult patients, across 3 clinics, with end-stage kidney disease (ESKD) on chronic hemodialysis (HD). Patients received high-flux HD for at least 1 year and then switched to HDx and were followed up for 1 year. Patients were excluded if they discontinued therapy, changed provider, underwent kidney transplant, recovered kidney function, or changed to peritoneal dialysis, another dialyzer, or renal clinic. Results: Twelve months after switching to HDx, the rate of hospitalization events per patient-year decreased from 0.77 (95% CI: 0.60–0.98, 61 events) to 0.71 (95% CI: 0.55–0.92, 57 events) (p = 0.6987). The hospital day rate per patient-year was significantly reduced from 5.94 days in the year prior to switching compared with 4.41 days after switching (p = 0.0001). The mean dose of erythropoiesis-stimulating agent (SC epoetin-α) and intravenous iron also significantly decreased (p = 0.0361 and p = 0.0003, respectively). Conclusion: Switching to HDx was associated with reductions in hospital day rate and medication use, suggesting HDx has the potential to reduce the burden of ESKD on patients and healthcare systems.

Management of iron deficiency anemia in hemodialysis patients based on mean corpuscular volume

BackgroundTo manage the anemic status in hemodialysis (HD) patients, a well-balanced combination therapy based on the use of erythropoiesis-stimulating agents (ESAs) and iron supplementation is essential. Serum ferritin level and transferrin saturation rate (TSAT) are the current standard tests for screening iron deficiency status. However, these are not included in frequently checked regular blood measurements in many HD centers. Other parameters that could predict a hemoglobin (Hb) increase response from iron supplementation have yet to be established. To determine a frequently checked and regularly measured biomarker for predicting iron deficiency status, this study investigated the value of mean corpuscular volume (MCV) as a clinical parameter for HD patients receiving intravenous iron supplementation (Fe-IV) therapy.Methods and resultsOne hundred thirty four HD patients, 88 non-HD patients with anemia, and 50 HD patients on Fe-IV therapy from the Nozatomon clinic were assessed. Comparison of MCV values of anemic HD patients and anemic non-chronic kidney disease (CKD) patients showed that anemic HD patients had significantly higher MCV values (93.9 ± 7.3 fL) compared with anemic non-CKD patients (82.8 ± 8.8fL). Fifty HD patients, who received Fe-IV therapy at ten consecutive HD sessions (inclusion criteria: Hb ≤ 12.0 g/dL, TSAT < 20%, and serum ferritin < 100 ng/mL) showed a rapid increase during the Fe-IV period in MCV, Hb, and TSAT levels. After the completion of the Fe-IV therapy, MCV persisted at the increased levels, whereas Hb levels further increased and peaked at 1 month with a gradual decline after, largely influenced by ESA dosage reductions. The 50 patients were divided into three groups according to the MCV levels obtained immediately prior to the Fe-IV therapy (MCV ≤ 85 fL, 85 fL < MCV ≤ 90 fL, MCV > 90 fL), and Hb changes at 50 days after the initiation of the Fe-IV therapy were compared. All the patients in the MCV ≤ 85 fL group and most of the patients in the 85 fL < MCV ≤ 90 fL group showed linear and consistent Hb increase during the 50-day period. In marked contrast, patients in the MCV > 90 fL group showed dispersed trends in their Hb increase. The present study also revealed that successful ESA dosage reduction could be achieved after the Fe-IV therapy in both the MCV ≤ 85 fL and 85 fL < MCV ≤ 90 fL groups.ConclusionsThe present study underscored the value of MCV in perceiving iron deficiency status as well as predicting iron-based therapeutic response in HD patients.

Daprodustat Compared with Epoetin Beta Pegol for Anemia in Japanese Patients Not on Dialysis: A 52-Week Randomized Open-Label Phase 3 Trial

Background: Daprodustat is an oral agent that stimulates erythropoiesis by inhibiting the prolyl hydroxylases which mark hypoxia-inducible factor for degradation through hydroxylation. Its safety and efficacy (noninferiority) were assessed in this 52-week, open-label study. Methods: Japanese patients not on dialysis (ND) (N = 299) with anemia of CKD (stages G3, G4, and G5) with iron parameters of ferritin >100 ng/mL or transferrin saturation >20% at screening were randomized to daprodustat or epoetin beta pegol (continuous erythropoietin receptor activator [CERA], also known as methoxy polyethylene glycol-epoetin beta). After initiation of the study, the daprodustat starting dose for erythropoiesis-stimulating agent (ESA)-naïve participants was revised, and daprodustat was started at 2 or 4 mg once daily depending on baseline hemoglobin. ESA users switched to daprodustat 4 mg once daily. CERA was started at 25 μg every 2 weeks for ESA-naïve patients and 25–250 μg every 4 weeks for ESA users based on previous ESA dose. In both treatment groups, dose was adjusted every 4 weeks based on hemoglobin level and changed according to a prespecified algorithm. The primary endpoint was mean hemoglobin level during weeks 40–52 in the intention-to-treat (ITT) population. ESA-naïve patients who entered before the protocol amendment revising the daprodustat starting dose were excluded from the ITT population. Results: Mean hemoglobin levels during weeks 40–52 were 12.0 g/dL in the daprodustat group (n = 108; 95% confidence interval [CI], 11.8–12.1) and 11.9 g/dL for CERA (n = 109; 95% CI 11.7–12.0); the difference between the groups was 0.1 g/dL (95% CI −0.1 to 0.3 g/dL). The lower limit of the 95% CI of the difference was greater than the prespecified margin of −1.0 g/dL. The mean hemoglobin level was within the target range (11.0–13.0 g/dL) during weeks 40–52 for 92% of participants in both groups. There was no meaningful difference in the frequencies of adverse events. Conclusions: Oral daprodustat was noninferior to CERA in achieving and maintaining target hemoglobin levels in Japanese ND patients. Daprodustat was well tolerated, with no new safety concerns identified.

Anemia in Chronic Kidney Disease : Role of Hypoxia Inducible Factor Stabilizer

A B S T R A C TAnemia contributes to increased morbidity and mortality in chronic kidney diseasepatients. The pathogenesis of anemia in these patients is multifactorial, but thecontribution of erythropoietin deficiency becomes greater as glomerular filtrationrate declines which related to decreased nephron mass. The current standard ofcare includes supplemental iron, erythropoiesis-stimulating agents (ESA), and redblood cell transfusions, although each has drawbacks. Lately, concern has arisenfollowing randomized clinical trials showing that higher hemoglobin targets and/orhigh ESA doses may cause significant harm including increasing cardiovascular andthrombotic events, and even death. Recent experimental and clinical studies showthe promising efficacy of hypoxia inducible factor (HIF) stabilizer which stimulatesendogenous erythropoietin production and enhance iron availability.

Anemia in Chronic Kidney Disease : Role of Hypoxia Inducible Factor Stabilizer

Anemia contributes to increased morbidity and mortality in chronic kidney disease patients. The pathogenesis of anemia in these patients is multifactorial, but the contribution of erythropoietin deficiency becomes greater as glomerular filtration rate declines which related to decreased nephron mass. The current standard of care includes supplemental iron, erythropoiesis-stimulating agents (ESA), and red blood cell transfusions, although each has drawbacks. Lately, concern has arisen following randomized clinical trials showing that higher hemoglobin targets and/or high ESA doses may cause significant harm including increasing cardiovascular and thrombotic events, and even death. Recent experimental and clinical studies show the promising efficacy of hypoxia inducible factor (HIF) stabilizer which stimulates endogenous erythropoietin production and enhance iron availability.

Factors associated with hepcidin-25 levels in maintenance hemodialysis patients.

This study aimed to investigate the factors that are independently associated with hepcidin-25 and its relationship with doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron in stable maintenance hemodialysis patients (smHD) stratified by ESAs administration. In 103 adult smHD (ESAs therapy (N=64) and ESAs-free (N=39)), median values of biologically active hepcidin-25 (chemiluminescent direct ELISA assay) and ferritin levels were significantly higher whereas red blood cell count, hemoglobin, and hematocrit values were lower in ESAs therapy compared to ESAs-free group (P < .001, for all). Our results suggest that ESAs-independent smHD exhibit supposedly normal hepcidin-25 levels and preserved iron homeostasis, with a lower degree of anemia. The results of our multivariable model indicate that hepcidin-25 levels are independently and positively associated with iron stores and inflammation, and inversely with active erythropoiesis, regardless of ESAs administration. Maintenance ESAs and the intravenous iron dose were not related to hepcidin-25 levels.

Plasma erythropoietin level and heart failure in patients undergoing peritoneal dialysis: a cross-sectional study

BackgroundRenal anemia is the important complication in patients undergoing peritoneal dialysis (PD), and heart failure (HF) is the important complication in patients on dialysis. Decreasing endogenous erythropoietin (EPO) in patients with chronic kidney disease is a major cause of renal anemia. On the other hand, high levels of EPO have been associated with the prognosis of patients with chronic HF. The association between plasma EPO and HF in patients on PD remains unclear. This study was designed to test our hypothesis that the plasma EPO level in patients on PD was associated with the markers of HF.MethodsWe investigated 39 patients undergoing PD at our hospital. We measured plasma EPO before erythropoiesis-stimulating agent (ESA) administration at the regular outpatient visits and then at 2 weeks after the final dose of ESA was administered and investigated the clinical factors. We estimated the correlations between the plasma EPO and the other parameters, and constructed univariate and multivariate logistic regression models for the risk for HF to estimate the effectiveness of plasma EPO and other factors on HF treatment in patients undergoing PD.ResultsThe plasma EPO concentration was positively correlated with the ESA dose and negatively correlated with serum ferrum, transferrin saturation, and body mass index and showed no correlation with other factors, such as the New York Heart Association (NYHA) classification and ferritin level. In univariate analysis, the factors significantly associated with HF risk were N-terminal pro-brain natriuretic peptide (NT-pro BNP), cardiothoracic ratio (CTR), serum creatinine (Cr), serum beta 2 microglobulin, dialysate dose, left ventricular mass index, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and weekly Kt/V. We performed a multivariate analysis with NT-pro BNP, Cr, and CTR, and all three factors were significant in the analysis.ConclusionThe plasma EPO level in patients undergoing PD was positively correlated with the monthly ESA dose and was not significant as a marker of HF, as judged with the NYHA classification. Therefore, the plasma EPO level may not be a useful marker for HF in patients undergoing PD.

Iron Therapy in Chronic Kidney Disease: Days of Future Past.

Anemia affects millions of patients with chronic kidney disease (CKD) and prompt iron supplementation can lead to reductions in the required dose of erythropoiesis-stimulating agents, thereby reducing medical costs. Oral and intravenous (IV) traditional iron preparations are considered far from ideal, primarily due to gastrointestinal intolerability and the potential risk of infusion reactions, respectively. Fortunately, the emergence of novel iron replacement therapies has engendered a paradigm shift in the treatment of iron deficiency anemia in patients with CKD. For example, oral ferric citrate is an efficacious and safe phosphate binder that increases iron stores to maintain hemoglobin levels. Additional benefits include reductions in fibroblast growth factor 23 levels and the activation of 1,25 dihydroxyvitamin D. The new-generation IV iron preparations ferumoxytol, iron isomaltoside 1000, and ferric carboxymaltose are characterized by a reduced risk of infusion reactions and are clinically well tolerated as a rapid high-dose infusion. In patients undergoing hemodialysis (HD), ferric pyrophosphate citrate (FPC) administered through dialysate enables the replacement of ongoing uremic and HD-related iron loss. FPC transports iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Moreover, this paper summarizes recent advancements of hypoxia-inducible factor prolyl hydroxylase inhibitors and future perspectives in renal anemia management.