Search Results (13)

Background: Anemia represents a significant complication in patients with advanced chronic kidney disease (CKD) on hemodialysis, primarily caused by reduced renal erythropoietin production. Despite erythropoiesis-stimulating agents (ESAs) being the cornerstone of treatment, hyporesponsiveness to these agents remains a clinical challenge with implications for patient outcomes. Objective: To identify and quantify risk factors associated with hyporesponsiveness to erythropoietin in patients with CKD on hemodialysis who present with anemia. Methods: This multicenter case–control study analyzed data from 784 hemodialysis patients receiving erythropoietin therapy across six dialysis centers in Ecuador between January and December 2019. Hyporesponsiveness was defined as requiring ≥ 200 IU/kg/week of erythropoietin alfa for ≥3 consecutive months to maintain target hemoglobin levels (10–12 g/dL). Demographic, clinical, and laboratory parameters were compared between hyporesponsive cases (n = 123) and responsive controls (n = 661). Bivariate and multivariate logistic regression analyses were performed to identify independent risk factors. Results: The prevalence of erythropoietin hyporesponsiveness was 15.69%. A multivariate analysis identified female sex (adjusted OR = 1.96; 95% CI: 1.20–3.20; p < 0.001), age < 50 years (adjusted OR = 4.25; 95% CI: 2.42–7.47; p < 0.001), serum albumin < 4.0 g/dL (adjusted OR = 10.53; 95% CI: 6.53–16.98; p < 0.001), ferritin ≥ 800 ng/mL (adjusted OR = 7.28; 95% CI: 4.22–12.57; p < 0.001), transferrin saturation < 20% (adjusted OR = 9.27; 95% CI: 5.47–15.69; p < 0.001), parathyroid hormone ≥ 500 pg/mL (adjusted OR = 1.89; 95% CI: 1.16–3.09; p = 0.011), and use of renin–angiotensin system blockers (adjusted OR = 2.25; 95% CI: 1.36–3.71; p = 0.002) as independent risk factors for erythropoietin hyporesponsiveness. Conclusions: Multiple demographic, clinical, and laboratory factors independently contribute to erythropoietin hyporesponsiveness in hemodialysis patients. Identification of these risk factors may guide clinicians in developing individualized treatment approaches, optimizing erythropoietin dosing, and implementing targeted interventions to improve anemia management in this vulnerable population. Full article

Background/Objectives: Inflammation may contribute to hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) and is often present in patients with chronic kidney disease (CKD). Roxadustat is approved in multiple countries for the treatment of anemia of CKD. This pooled analysis evaluated the efficacy and safety of roxadustat in patients with dialysis-dependent (DD) or non-dialysis-dependent (NDD) CKD by inflammation status. Methods: Data from five studies comparing roxadustat versus ESAs were pooled by patient populations in this analysis (NDD: DOLOMITES; DD: ROCKIES, SIERRAS, HIMALAYAS, PYRENEES). The mean change from baseline in hemoglobin levels to Weeks 28–52 and mean weekly dose of roxadustat or ESA at Week 24 were assessed by baseline inflammation levels (determined by high-sensitivity C-reactive protein [hsCRP] levels, divided into quintiles). Safety data were summarized descriptively. Results: In total, 613 patients with NDD CKD (roxadustat n = 320; ESA n = 293) and 4072 patients with DD CKD (roxadustat n = 2022; ESA n = 2050) were evaluated. Roxadustat increased hemoglobin levels in a manner similar to ESAs, independent of baseline inflammation status. In both the NDD and DD populations, roxadustat doses did not increase at Week 24 in patients with higher hsCRP levels at baseline. Patients with high baseline hsCRP levels required greater ESA doses at Week 24 compared with patients who had lower baseline hsCRP levels in both patient populations. The incidence rates of treatment-emergent adverse events were generally comparable with those of roxadustat and ESA across hsCRP quintiles in both the NDD and DD populations. Conclusions: Roxadustat addresses the multiple causes of anemia of CKD, regardless of inflammatory status, without requiring dose increases. Full article

Background/Objectives: Renal anemia is one of the major complications associated with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are commonly used; however, some patients exhibit resistance. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) have emerged as a novel treatment for renal anemia, enhancing erythropoiesis and iron metabolism. Methods: We retrospectively analyzed laboratory data related to erythropoiesis from 105 patients with CKD before and after treatment with HIF-PHI or ESA. The dialysis initiation and mortality rates were also assessed over a median follow-up of 614 days. Results: HIF-PHI and ESA significantly increased the hemoglobin levels within 6 months of treatment (9.5 ± 1.0 to 10.7 ± 1.1, p < 0.01, and 9.9 ± 1.5 to 10.7 ± 1.2 g/dL, p < 0.01, respectively). The HIF-PHI group demonstrated a significant decrease in red cell distribution width (14.5 ± 1.9% to 13.8 ± 1.4%, p < 0.01), suggesting improved erythropoiesis, and exhibited a lower cumulative incidence of outcomes. The aged-adjusted multivariate analysis confirmed the independent association between HIF-PHI treatment and reduced risk of cumulative outcome (p = 0.042). Conclusions: HIF-PHIs can serve as an alternative to ESA for managing renal anemia in CKD, improving both hematological parameters and long-term outcomes. Full article

Background/Objectives: Besides a multitude of consequences patients on chronic renal replacement therapy have, anemia is one of the most prominent factors making a significant number of patients dependent on erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to examine the relationship between the levels of a broad spectrum of thrombo-inflammatory and oxidative stress-related biomarkers and the presence and level of ESA hyporesponsiveness in patients undergoing regular chronic hemodialysis. Methods: This cross-sectional study included 96 patients treated with chronic hemodialysis. Levels of several thrombo-inflammatory and oxidative stress-related biomarkers, as well as demographic, clinical, and laboratory analyses, were collected and analyzed based on the calculated value of the ESA-hyporesponsiveness index (EHRI). Results: In the analyzed sample, 58 patients received ESAs. Of all the investigated parameters, only body mass index (BMI), level of plasminogen activator inhibitor-1, and level of L-type fatty acid binding protein (L-FABP) were observed as significant predictors of EHRI. A significant diagnostic potential for ESA resistance has been observed in BMI and L-FABP between ESA-resistant and ESA-non-resistant groups of patients (p = 0.004, area under the curve 0.763 and p = 0.014, area under the curve 0.712, respectively) with the cut-off values of 25.46 kg/m² and 5355.24 ng/mL, respectively. Having a BMI of 25.46 kg/m² or less and an L-FABP level higher than 5355.24 ng/mL were observed as significant predictors of ESA resistance (odds ratio 9.857 and 6.125, respectively). Conclusions: EHRI was positively predicted by low BMI and high levels of plasminogen activator inhibitor-1 and L-FABP. High levels of L-FABP and low BMI have been observed as strong predictors of ESA resistance. Full article

Traditionally, the treatment of anemia associated with chronic kidney disease (CKD) involves prescribing erythropoiesis-stimulating agents (ESAs) or iron preparations. The effectiveness and safety of ESAs and iron have been established. However, several clinical issues, such as hyporesponsiveness to ESAs or defective iron utilization for erythropoiesis, have been demonstrated. Recently, a new class of therapeutics for renal anemia known as hypoxia-inducible factor (HIF)/proline hydroxylase (PH) inhibitors has been developed. Several studies have reported that HIF-PH inhibitors have unique characteristics compared with those of ESAs. In particular, the use of HIF-PH inhibitors may maintain target Hb concentration in patients treated with a high dose of ESAs without increasing the dose. Furthermore, several recent studies have demonstrated that patients with CKD with defective iron utilization for erythropoiesis had a high risk of cardiovascular events or premature death. HIF-PH inhibitors increase iron transport and absorption from the gastrointestinal tract; thus, they may ameliorate defective iron utilization for erythropoiesis in patients with CKD. Conversely, several clinical problems, such as aggravation of thrombotic and embolic complications, diabetic retinal disease, and cancer, have been noted at the time of HIF-PH inhibitor administration. Recently, several pooled analyses of phase III trials have reported the non-inferiority of HIF-PH inhibitors regarding these clinical concerns compared with ESAs. The advantages and issues of anemia treatment by ESAs, iron preparations, and HIF-PH inhibitors must be fully understood. Moreover, patients with anemia and CKD should be treated by providing a physiological erythropoiesis environment that is similar to that of healthy individuals. Full article

The trace element zinc is essential for diverse physiological processes in humans. Zinc deficiency can impair growth, skin reproduction, immune function, maintenance of taste, glucose metabolism, and neurological function. Patients with chronic kidney disease (CKD) are susceptible to zinc deficiency, which is associated with erythropoiesis-stimulating agent (ESA) hypo-responsive anemia, nutritional problems, and cardiovascular diseases as well as non-specific symptoms such as dermatitis, prolonged wound healing, taste disturbance, appetite loss, or cognitive decline. Thus, zinc supplementation may be useful for the treatment of its deficiency, although it often causes copper deficiency, which is characterized by several severe disorders including cytopenia and myelopathy. In this review article, we mainly discuss the significant roles of zinc and the association between zinc deficiency and the pathogenesis of complications in patients with CKD. Full article

Anemia in chronic kidney disease (CKD) has become an important clinical issue with the increased prevalence of elderly patients living with CKD progressing to kidney failure. The causes of anemia in elderly individuals tend to be multifactorial, exacerbated by the physiological effects of aging, frailty and declining kidney function. Erythropoiesis-stimulating agents (ESAs) are the conventional therapeutic option for anemia in CKD. However, ESA hyporesponsiveness is a commonly observed issue in clinical practice and an issue that is more challenging to resolve in elderly patients living with frailty, kidney disease, and multi-morbidities. Following the emergence of oral hypoxia-induced factor prolyl-hydroxylase inhibitors (HIF-PHI) in recent years, there is discussion on whether it is a solution to the conundrum of ESA hyporesponsiveness, as HIF-PHI treats anemia via an alternative physiological pathway. There remains uncertainty on the suitability of HIF-PHI use in elderly patients, given a lack of data on its safety over long-term follow-up for the elderly population. Further study is needed to provide answers, considering the clinical significance of this issue within a public-health scale. Full article

Each patient undergoing maintenance haemodialysis (MHD) has a different response to erythropoiesis-stimulating agents (ESAs). Haemodilution due to fluid overload has been shown to contribute to anaemia. Body mass index (BMI) has been shown to influence ESA response in dialysis patients; however, BMI calculation does not distinguish between fat and lean tissue. The association between lean muscle mass and erythropoietin hyporesponsiveness is still not well-known among MHD patients. We designed a cross-sectional study and used bioimpedance spectroscopy (BIS) to analyse the relationship between body composition, haemoglobin level, and erythropoietin resistance index (ERI) in MHD patients. Seventy-seven patients were enrolled in the study group. Compared with patients with haemoglobin ≥ 10 g/dL, those with haemoglobin < 10 g/dL had higher serum ferritin levels, malnutrition–inflammation scores (MIS), relative overhydration, ESA doses, and ERIs. In multivariate logistic regression, higher ferritin levels and MIS were the only predictors of lower haemoglobin levels. The ERI was significantly positively correlated with age, Kt/V, ferritin levels, and MIS and negatively correlated with albumin levels, BMI, and lean tissue index (LTI). Multivariate linear regression analysis revealed that ferritin levels, BMI, and LTI were the most important predictors of ERI. In MHD patients, using BIS to measure body composition can facilitate the development of early interventions that aim to prevent sarcopenia, support ESA responsiveness, and, consequently, improve anaemia management. Full article

Chronic kidney disease (CKD) is one of the fastest-growing major causes of death internationally. Better treatment of CKD and its complications is crucial to reverse this negative trend. Anemia is a frequent complication of CKD and is associated with unfavorable clinical outcomes. It is a devastating complication of progressive kidney disease, that negatively affects also the quality of life. The prevalence of anemia increases in parallel with CKD progression. The aim of this review is to summarize the current knowledge on therapy of renal anemia. Iron therapy, blood transfusions, and erythropoietin stimulating agents are still the mainstay of renal anemia treatment. There are several novel agents on the horizon that might provide therapeutic opportunities in CKD. The potential therapeutic options target the hepcidin–ferroportin axis, which is the master regulator of iron homeostasis, and the BMP-SMAD pathway, which regulates hepcidin expression in the liver. An inhibition of prolyl hydroxylase is a new therapeutic option becoming available for the treatment of anemia in CKD patients. This new class of drugs stimulates the synthesis of endogenous erythropoietin and increases iron availability. We also summarized the effects of prolyl hydroxylase inhibitors on iron parameters, including hepcidin, as their action on the hematological parameters. They could be of particular interest in the out-patient population with CKD and patients with ESA hyporesponsiveness. However, current knowledge is limited and still awaits clinical validation. One should be aware of the potential risks and benefits of novel, sophisticated therapies. Full article

Anemia is a well-known consequence of chronic kidney disease (CKD); it is mainly due to a relative insufficiency of erythropoietin synthesis by the failing kidneys. Over the years, the combination of erythropoiesis stimulating agents (ESA) and iron has become the standard of care of anemia. All ESAs effectively increase hemoglobin (Hb) levels in a substantial percentage of patients. However, in the last decade, their use has been surrounded by safety issues in increased cardiovascular risk, especially when used at high doses in inflamed and hyporesponsive patients. This has led to the definition of a more cautious Hb target. Iron deficiency is very frequent in CKD patients, with a higher frequency in non-dialysis patients. Traditionally, iron supplementation is mostly used as supportive therapy for anemia control. However, the concept is growing that intravenous iron therapy per se could be beneficial in the presence of heart failure. A new class of drugs, prolyl hydroxylase domain (PHD) inhibitors (PHD inhibitors) is becoming available for the treatment of anemia in CKD patients. Theoretically, these agents have a number of advantages, the main ones being that of stimulating the synthesis of endogenous erythropoietin and increasing iron availability. The impact of their future use in clinical practice is still to be defined. Another possible strategy could be targeting serum hepcidin and its related pathways. This possibility is fascinating from the scientific point of view, but at present its development phase is still far from clinical application. Full article

Anemia is frequently observed in the course of chronic kidney disease (CKD) and it is associated with diminishing the quality of a patient’s life. It also enhances morbidity and mortality and hastens the CKD progression rate. Patients with CKD frequently suffer from a chronic inflammatory state which is related to a vast range of underlying factors. The results of studies have demonstrated that persistent inflammation may contribute to the variability in Hb levels and hyporesponsiveness to erythropoietin stimulating agents (ESA), which are frequently observed in CKD patients. The understanding of the impact of inflammatory cytokines on erythropoietin production and hepcidin synthesis will enable one to unravel the net of interactions of multiple factors involved in the pathogenesis of the anemia of chronic disease. It seems that anti-cytokine and anti-oxidative treatment strategies may be the future of pharmacological interventions aiming at the treatment of inflammation-associated hyporesponsiveness to ESA. The discovery of new therapeutic approaches towards the treatment of anemia in CKD patients has become highly awaited. The treatment of anemia with erythropoietin (EPO) was associated with great benefits for some patients but not all. Full article

Anemia is one of the most common problems in chronic kidney disease (CKD). In several cases, despite comprehensive investigations, definite causes of anemia frequently remain unknown. We aimed to analyze the factors that possibly affect anemia in CKD patients who were referred for hematology consultation. A total of 87 patients were retrospectively included in the cohort. Forty-four cases were excluded, 30 cases with unavailable intact parathyroid hormone (iPTH) data, 11 cases with bone marrow diseases (8 Pure red cell aplasia, 3 Myelodysplastic syndrome) and 3 cases with thalassemia. Totally, 43 patients were analyzed. Patients with high iPTH had significantly lower Hemoglobin (Hb) level and required higher dose of erythropoietin stimulating agents (ESAs) compared with normal iPTH group (Hb 8.29 vs. 9.24 mg/dL, p = 0.032 and ESAs dose of 16,352.94 vs. 12,444.44 U/ week, p = 0.024). In univariate followed by stepwise multivariate analysis, serum phosphate (PO4) was significantly associated with lower Hb level (p = 0.01 and p = 0.013, respectively). Hb level was inversely correlated with iPTH and PO4 level (r = −0.54, p < 0.001 and r = −0.47, p = 0.05; respectively). Mineral disequilibrium is an important factor associated with anemia in ESA hyporesponsive CKD. Hyperphosphatemia and secondary hyperparathyroidism are significantly correlated with low Hb. Therefore, we strongly suggest correction of these mineral disequilibrium factors prior to performing bone marrow study. Full article

Background: In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). Methods: Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL). Results: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. Conclusions: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels. Full article