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1.
The association of erythropoietin-stimulating agents and increased risk for AV-fistula dysfunction in hemodialysis patients. A retrospective analysis.
Wärme, A, Hadimeri, H, Nasic, S, Stegmayr, B
BMC nephrology. 2021;(1):30
Abstract
BACKGROUND Patients in maintenance hemodialysis (HD) need a patent vascular access for optimal treatment. The recommended first choice is a native arteriovenous fistula (AVF). Complications of AVF are frequent and include thrombosis, stenosis and infections leading to worsening of dialysis efficacy. Some known risk factors are age, gender and the presence of diabetes mellitus. The aim was to investigate if further risk variables are associated with dysfunctional AVF. METHODS This retrospective observational study included 153 chronic HD patients (Cases) referred to a total of 473 radiological investigations due to clinically suspected complications of their native AVF. Another group of chronic HD patients (n = 52) who had a native AVF but were without history of previous complications for at least 2 years were controls. Statistical analyses included ANOVA, logistic regression, parametric and non-parametric methods such as Student's T-test and Mann-Whitney test. RESULTS Among Cases, at least one significant stenosis (> 50% of the lumen) was detected in 348 occasions. Subsequent PTA was performed in 248 (71%). Median erythropoiesis-stimulating agent (ESA) weekly doses were higher in Cases than in Controls (8000 vs 5000 IU, p < 0.001). Cases received higher doses of intravenous iron/week than the Controls before the investigation (median 50 mg vs 25 mg, p = 0.004) and low molecular weight heparin (LMWH, p = 0.028). Compared to Controls, Cases had a lower level of parathyroid hormone (median 25 vs 20 ρmol/L, p = 0.009). In patients with diabetes mellitus, HbA1c was higher among Cases than Controls (50 vs 38 mmol/mol, p < 0.001). Multiple regression analysis revealed significant associations between Cases and female gender, prescription of doxazocin, and doses of ESA and LMWH. There was no difference between the groups regarding hemoglobin, CRP or ferritin. CONCLUSION In conclusion, the present study indicated that the factors associated with AVF problems were high doses of ESA, iron administration, and tendency of thromboembolism (indicated by high LMWH doses); the use of doxazocin prescription, however, requires further investigation.
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2.
Factors associated with hepcidin-25 levels in maintenance hemodialysis patients.
Savković, M, Simić-Ogrizović, S, Dopsaj, V
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2021;(5):565-574
Abstract
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.
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3.
In Search of Predictors of Switching Between Erythropoiesis-Stimulating Agents in Clinical Practice: A Multi-Regional Cohort Study.
Ingrasciotta, Y, Belleudi, V, Trotta, F, Addis, A, Fontana, A, Chinellato, A, Ientile, V, Tari, DU, Roberto, G, Pastorello, M, et al
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. 2020;(1):55-64
Abstract
BACKGROUND AND OBJECTIVES Switching between different erythropoiesis-stimulating agents (ESAs) during the first year of therapy is frequent (15-20%), much more so toward reference products than biosimilars. The objectives of this study were to investigate the frequency and identify the potential predictors of switching between biosimilar and originator ESAs during the first year of treatment in patients with chronic kidney disease (CKD), or chemotherapy-related anemia from six large Italian geographic areas in the years 2009-2015. METHODS A retrospective cohort study was conducted using six Italian regional claims databases (≥ 13 million inhabitants) during 2009-2015. Among incident epoetin users, the frequency of single, multiple, and backward switch during the first year of treatment was evaluated. Using frailty Cox models, potential predictors of first switch were identified. All analyses were stratified by the main indications for use. RESULTS Among 102,240 incident epoetin users, 15,853 (15.5%) switched to another epoetin during the first year of therapy; only 18% of these switched to biosimilars. Single switch was more common (62.2% of the switchers) than multiple (23.5%) or backward switch (14.3%). In cancer, the cumulative number of transfusions and iron preparations dispensed, as well as hyperparathyroidism, were predictors of switching. In CKD, the cumulative number of transfusions, number of vitamin A/D preparations dispensed, and CKD severity increased the probability of switching. CONCLUSIONS Switching between ESAs was frequent in both CKD and cancer patients. The number of cumulative transfusions and severity of disease seemed to affect the switch.
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4.
Anemia management in non-menopausal women in a primary care setting: a prospective evaluation of clinical practice.
Bayen, S, Le Grand, C, Bayen, M, Richard, F, Messaadi, N
BMC family practice. 2020;(1):13
Abstract
BACKGROUND The study aimed to analyze anemia management in non-pregnant, and non-menopausal women aged from 18 to 50 years old, in a French primary care setting. METHODS An observational descriptive prospective study was conducted between November 2018 and February 2019. Inclusion criteria were as followed: anemia diagnosed in women aged from 18 to 50, not pregnant and not menopausal. Quantitative and qualitative data were anonymized and collected through an electronic survey. Investigating general practitioners completed the questionnaire for each newly diagnosed woman. Mean values and medians were calculated for the quantitative data. Answers to the open questions were encoded manually and proportions of the different modalities have been calculated. RESULTS Altogether, 43 women with anemia were ascertained. Moderate microcytic anemia, due to an iron deficiency in a context of menorrhagia, was the most observed anemia profile. The mean value of hemoglobin was 10.5 ± 1 g/dl. Among these women: 32 (74%) presented an iron deficiency, 17 (53%) had inappropriate intakes, and 9 (28%) reported menorrhagia. For 17 (40%) women, unnecessary or inappropriate exams were prescribed. The investigations did not allow to establish a differential diagnosis for 12 women (28%). Even for similar clinical situations, anemia management was variable. Among the women who presented iron deficiency, 15 (47%) were informed about an iron-rich diet and received a daily iron supplementation of ferrous sulfate between 80 mg and 160 mg. CONCLUSIONS Our study highlights that, in the absence of specific national guidelines for anemia management in non-pregnant, non-menopausal women in primary care settings, French GPs undergo various clinical management strategies leading to a heterogeneous, sometimes inappropriate follow-up. Women with iron deficiency were prescribed higher daily iron supplementation than recommended, according to new evidence, suggesting a maximal daily dose of 50 mg of elementary iron in a context of Hepcidin up-regulation in the case of an iron overload. Additional longitudinal studies with a bigger sample size and randomized controlled trials are needed to confirm our results and to elaborate national guidelines.
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5.
[Assessment of iron deficiency anemia management in the general hospital of Grenoble: A 12-month follow-up of an intravenous ferric carboxymaltose treatment program in a cohort of patients with non-dialysis-dependent chronic kidney disease].
Romanet, T, Bedouch, P, Zaoui, P
Nephrologie & therapeutique. 2019;(2):104-109
Abstract
INTRODUCTION The FIND-CKD study has validated the use of ferric carboxymaltose (FCM) injection with a target of ferritin level between 400 and 600ng/mL to treat iron deficiency anemia in non-dialysis-dependent chronic kidney disease (ND-CKD) patients. In order to assess this strategy in clinical practice, we constituted a cohort of patients within our nephrology department. PATIENTS AND METHODS Patients had CKD stages 3 to 5, hemoglobin level (Hb)<13g/dL (men) or<12g/dL (women), and ferritin level (F)<100ng/mL or transferrin saturation (TSAT)<20%. They were not treated by erythropoiesis-stimulating agent (ESA) for at least one month, and oral iron had been poorly tolerated or ineffective. FCM first dose was adjusted according to patient weight. A new infusion was possible, at least one month after the first, with a half-dose if TSAT<20% but F≥200ng/mL; no perfusion was performed if F≥400ng/mL. RESULTS In all, 53 patients were included with a mean Hb of 11.4g/dL and a mean TSAT of 16%. Over one year of follow-up, only 12 patients (22.6%) needed another treatment for anemia (blood transfusion or ESA). No patient showed a significant decrease in Hb. In all, 62% of patients received only one infusion of FCM. CONCLUSION The administration of FCM IV with ferritin levels in the recommended target has proven effective in correcting anemia of ND-CKD patients while limiting the use of another therapeutic strategy.
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Long-term maintenance of hemoglobin levels in hemodialysis patients treated with bi-weekly epoetin beta pegol switched from darbepoetin alfa: a single-center, 12-month observational study in Japan.
Kawai, T, Kusano, Y, Yamada, K, Ueda, C, Kawai, A, Masaki, T
Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs. 2019;(2):146-153
Abstract
Recent evidence on maintenance administration of epoetin beta pegol, a continuous erythropoiesis receptor activator (CERA), in dialysis patients shows the clinical benefit of bi-weekly administration (Q2W) in improving hematopoiesis and iron use efficiency. We undertook a single-center observational study of 33 Japanese maintenance dialysis patients, whose anemia had been kept stable through weekly administration (Q1W) of darbepoetin (DA), to evaluate the effectiveness of CERA Q2W switched from DA in maintaining hemoglobin (Hb) levels over a 12-month period. The target Hb level was 10.0-12.0 g/dL. Throughout the 12-month period, the mean Hb was stably maintained at 10.5-10.8 g/dL, 69.7-87.9% of the patients achieving the target Hb level. The mean CERA dose was within the range of 62.9-78.8 µg/2 weeks. The average CERA dose adjustment frequency after switching was low at 0.42-0.67 times/3 months. In both subgroups stratified by the DA dose prior to the switch, Hb levels were kept stable during CERA administration; however, in the low-dose group (10-20 µg/week of DA), the CERA and iron doses decreased over time, whereas in the high-dose group (30-60 µg/week of DA) they remained unchanged. CERA Q2W achieved long-term successful anemia management in Japanese maintenance dialysis patients after switching from DA Q1W. CERA dose was adjusted based on an overall consideration of past changes in Hb levels, erythropoiesis-stimulating agent and iron doses. Subgroup analysis showed the CERA dose in the low-dose group decreased continuously, due possibly to a long-term improvement in iron use efficiency.
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7.
Butyrylcholinesterase level as an independent factor of erythropoiesis-stimulating agent resistance in patients on maintenance hemodialysis: a single-center cross-sectional study.
Okamoto, T, Hatakeyama, S, Tanaka, Y, Imanishi, K, Takashima, T, Saitoh, F, Koie, T, Suzuki, T, Ohyama, C
Clinical and experimental nephrology. 2018;(5):1174-1181
Abstract
BACKGROUND Erythropoiesis-stimulating agent (ESA) responsiveness is related to the nutritional status of patients on hemodialysis (HD). Serum butyrylcholinesterase (BChE), an alpha-glycoprotein, may decrease in case of malnutrition. We investigated whether BChE was independently related to ESA resistance in patients on HD. METHODS The laboratory data and ESA resistance index (ERI), defined as ESA dosage per week divided by dry weight and hemoglobin, were investigated in 215 patients on HD between July and September 2017. Malnutrition was defined as Geriatric Nutritional Risk Index (GNRI) of < 91.2. The patients were stratified into two groups: ERI-high (ERI ≥ 9.44) and ERI-low (ERI < 9.44) groups. Variables such as patient's background, medication, and laboratory data were compared between the two groups. The optimal cutoff value of BChE for higher ERI was determined using receiver operating characteristic analysis. Factors independently associated with higher ERI were determined using multivariate logistic regression analysis. RESULTS The median and optimal cutoff values of ERI and BChE were 6.51 and 200 IU/L, respectively. The study included 71 (33%) and 144 (67%) patients in the ERI-high and ERI-low groups, respectively. Significant between-group differences were observed concerning age, hemoglobin, ESA dose, lipid profiles, serum albumin, body mass index, GNRI, iron metabolism markers, ferric medicines, and BChE. Multivariate analysis showed that BChE < 200 IU/L (odds ratio 3.67; 95% confidence interval 1.73-7.77) continued to be an independent factor associated with higher ERI after adjusting for potential confounders, which was a similar odds ratio as GNRI < 91.2. CONCLUSION BChE may be an independent indicator of ESA resistance.
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8.
Anemia and mortality in patients with nondialysis-dependent chronic kidney disease.
Stirnadel-Farrant, HA, Luo, J, Kler, L, Cizman, B, Jones, D, Brunelli, SM, Cobitz, AR
BMC nephrology. 2018;(1):135
Abstract
BACKGROUND A combination of safety concerns and labeling changes impacted use of erythropoiesis-stimulating agents (ESAs) in renal anemia. Data regarding contemporary utilization in pre-dialysis chronic kidney disease (CKD) are lacking. METHODS Electronic healthcare records and medical claims data of pre-dialysis CKD patients were aggregated from a large US managed care provider (2011-13). ESA use patterns, characteristics, and outcomes of ESA-treated/untreated patients were quantified. RESULTS At baseline, 109/32,308 patients (0.3%) were ESA users. Treated patients were older, had more advanced CKD (58.8% vs 5.4% with stage 4/5 vs 3) and greater prevalence of comorbid diabetes, hypertension, heart failure, and peripheral vascular disease. An additional 266 patients initiated ESA: hemoglobin at initiation was 8-10 g/dL in 193 of these and >10 g/dL in the remainder; 61.7% had stage 4/5 CKD; prevalence of cardiovascular disease was high (50.8% heart failure; 25.2% prior myocardial infarction; 24.1% prior stroke). During follow-up, rates of death and cardiovascular events were higher in baseline ESA users and ESA naives versus non-users. CONCLUSIONS ESA use in pre-dialysis CKD patients was exceedingly rare and directed disproportionately to older, sicker patients; these patients had high rates of death and cardiovascular events. These data provide context for contemporary use of ESA in pre-dialysis CKD.
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9.
Anemia Management among Hemodialysis Patients with High Ferritin Levels.
Einbinder, Y, Agur, T, Davidov, K, Zitman-Gal, T, Golan, E, Benchetrit, S
The Israel Medical Association journal : IMAJ. 2018;(7):405-411
Abstract
BACKGROUND Anemia management strategies among chronic hemodialysis patients with high ferritin levels remains challenging for nephrologists. OBJECTIVES To compare anemia management in stable hemodialysis patients with high (≥ 500 ng/ml) vs. low (< 500 ng/ml) ferritin levels. METHODS In a single center, record review, cohort study of stable hemodialysis patients who were followed for 24 months, an anemia management policy was amended to discontinue intravenous (IV) iron therapy for stable hemodialysis patients with hemoglobin > 10 g/dl and ferritin ≥ 500 ng/ml. Erythropoiesis-stimulating-agents (ESA), IV iron doses, and laboratory parameters were compared among patients with high vs. low baseline ferritin levels before and after IV iron cessation. RESULTS Among 87 patients, 73.6% had baseline ferritin ≥ 500 ng/ml. Weekly ESA dose was greater among patients with high vs. low ferritin (6788.8 ± 4727.8 IU/week vs. 3305.0 ± 2953.9 IU/week, P = 0.001); whereas, cumulative and monthly IV iron doses were significantly lower (1628.2 ± 1491.1 mg vs. 2557.4 ± 1398.9 mg, P = 0.011, and 82.9 ± 85 vs. 140.7 ± 63.9 mg, P = 0.004). Among patients with high ferritin, IV iron was discontinued for more than 3 months in 41 patients (64%) and completely avoided in 6 (9.5%).ESA dose and hemoglobin levels did not change significantly during this period. CONCLUSIONS Iron cessation in chronic hemodialysis patients with high ferritin levels did not affect hemoglobin level or ESA dose and can be considered as a safe policy for attenuating the risk of chronic iron overload.
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10.
A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy.
Huang, LL, Lee, D, Troster, SM, Kent, AB, Roberts, MA, Macdougall, IC, McMahon, LP
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2018;(9):1628-1635
Abstract
BACKGROUND Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD). METHODS Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed. RESULTS Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both). CONCLUSIONS Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.