The role of erythropoietin to prevent red blood cell transfusion in a 2018-2020 two-center cohort of preterm infants.

BACKGROUND: Treatment with recombinant human erythropoietin (rHu-EPO) modestly prevented packed red blood cell transfusions (pRBCTs) in preterm infants in studies performed several years ago. In France, some neonatal units stopped using rHu-EPO, while others continued. The aim of this study was to explore the role of rHu-EPO in the prevention of pRBCTs in a recent cohort of preterm infants. MATERIALS AND METHODS: Preterm infants who met rHu-EPO indications and were hospitalised between 2018 and 2020 in two neonatal units -one that did not use rHu-EPO and another that did- were eligible. Data about the neonatal history, rHu-EPO and iron treatments and pRBCT indications and volumes were collected. Infants exposed and not exposed to rHu-EPO were compared in univariate and multivariate analyses using backward logistic regression and Cox proportional hazards regression. RESULTS: A total of 257 patients exposed to rHu-EPO and 285 patients who were not exposed were included. Three profiles emerged. In the infants with a gestational age <28 weeks, the cumulative pRBCT volume/kg was similar regardless of rHu-EPO exposure (mean difference -2.8 mL, 95% confidence interval -16.1, 10.5, p=0.68). In the infants born between 28 and 30 weeks, a late pRBCT was prevented in the rHu-EPO group (single pRBCT: no rHu-EPO 22.1% vs rHu-EPO 8%, p=0.003). However, rHu-EPO was not independently associated with avoidance of this pRBCT. Finally, the need for pRBCT was low in the infants born after 30 weeks of gestation, making rHu-EPO treatment futile. In contrast, early iron supplementation was revealed to be critical in preventing pRBCT. DISCUSSION: No benefit of rHu-EPO in preventing pRBCT was observed in our cohort. The place of rHu-EPO in future requires careful consideration of the population concerned, adjustment of the therapeutic schedule and evolution of the indications for pRBCT.

Effect of long-term treatment with trivalent chromium on erythropoietin production in HepG2 cells.

Trivalent chromium (Cr(III)) is sometimes taken as a long-term supplement, but its effectiveness is unclear. Recently, Cr(III) reportedly modulates peroxisome proliferator-activated receptor gamma (PPARγ) expression. Our previous study reported that increased PPARγ after 24 h Cr(III) treatment promoted erythropoietin (EPO) production in HepG2 cells. In the current study, we analyzed 4-week Cr(III) treatment effects on PPARγ and EPO production in HepG2 cells. Long-term Cr(III) treatment resulted in significantly elevated mRNA expression levels of PPARγ and EPO compared to controls. Additionally, treatment with a PPARγ inhibitor suppressed EPO mRNA expression. Increased EPO mRNA expression due to stimulation with hypoxia or cobalt was unaffected by long-term Cr(III) treatment. Administration of lipopolysaccharide and pyocyanin which causes oxidative stress, promoted EPO production, but this effect was attenuated in cells treated with Cr(III). Long-term Cr(III) treatment increased hypoxia inducible factor (HIF)-1α and 2α mRNA expression and protein levels. Increased PPARγ, induced by long-term Cr(III) treatment, suppressed sirtuin1 (SIRT1) mRNA expression and increased EPO mRNA expression, suggesting that increased PPARγ attenuated the suppressive effect of SIRT1 on HIF. These results suggest that the sustained increase in PPARγ during long-term Cr(III) treatment maintains increased EPO production through a mechanism different from that observed under hypoxia.

Fatigue visual analogue scale score correlates with quality of life in cancer patients receiving epoetin alfa (Sandoz) for chemotherapy-induced anaemia: The CIROCO study.

PURPOSE: Available tools to measure fatigue and health-related quality of life (HRQoL) in cancer patients are often difficult to use in clinical practice. The fatigue visual analogue scale (VAS) provides a simple method to assess fatigue. This study evaluated the correlation between HRQoL and fatigue perceived by cancer patients undergoing chemotherapy. METHODS: This was a non-interventional prospective study of adult cancer patients in France presenting with chemotherapy-induced anaemia (CIA) treated with epoetin alfa (Sandoz). Data were collected using an electronic case report form at study inclusion (T0), after 2-3 chemotherapy cycles (T1) and after 4-6 cycles (T2). RESULTS: The study included 982 patients from September 2015 to October 2017. Overall, there was a negative correlation between fatigue VAS and HRQoL. The overall haemoglobin (Hb) change between T0 and T2 was +17.8 % (± 18.1 %). Fatigue assessed by both patients and physicians showed a clinically significant improvement during the study. Global HRQoL also increased. CONCLUSION: Treatment of CIA with epoetin alfa (Sandoz) improved Hb levels, fatigue, and HRQoL, with a correlation observed between fatigue VAS score and HRQoL. Fatigue VAS could act as a simple alternative to more complex methods to measure HRQoL; however, further analyses are required to confirm this association.

Anemia, Iron Supplementation, and the Brain.

The developing brain is particularly vulnerable to extrinsic environmental events such as anemia and iron deficiency during periods of rapid development. Studies of infants with postnatal iron deficiency and iron deficiency anemia clearly demonstrated negative effects on short-term and long-term brain development and function. Randomized interventional trials studied erythropoiesis-stimulating agents and hemoglobin-based red blood cell transfusion thresholds to determine how they affect preterm infant neurodevelopment. Studies of red blood cell transfusion components are limited in preterm neonates. A biomarker strategy measuring brain iron status and health in the preanemic period is desirable to evaluate treatment options and brain response.

An updated meta-analysis on the efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor treatment of anemia in nondialysis-dependent chronic kidney disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia.

Hydrophobic constituents of Polygonum multiflorum roots promote renal erythropoietin expression in healthy mice.

The roots of Polygonum multiflorum Thunberg (Polygonaceae) are used as a crude drug Kashu that is considered to improve blood deficiency based on a Kampo concept. Kashu has been included in Kampo formulas, such as Tokiinshi, which is used to treat eczema and dermatitis with itchiness by inhibiting inflammation and facilitating blood circulation in the skin. However, the effects of P. multiflorum roots on erythropoiesis are unclear. Previously, we isolated six phenolic constituents from an ethyl acetate (EtOAc)-soluble fraction of P. multiflorum root extract and identified them as (E)-2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucopyranoside [(E)-THSG], emodin, emodin-8-O-ß-D-glucopyranoside, physcion, physcion-8-O-ß-D-glucopyranoside, and catechin. To examine whether P. multiflorum roots facilitate erythropoiesis, the EtOAc-soluble fraction was orally administered to healthy ICR mice. When compared with mice fed a standard diet alone (Controls), the mice fed a diet including the EtOAc-soluble fraction exhibited significantly higher serum erythropoietin (Epo) levels. The renal Epo mRNA levels in EtOAc-soluble fraction-administered mice were significantly higher than those in the control mice. Then, we administered roxadustat, which is a drug to treat the patient suffering with renal anemia by specifically inhibiting hypoxia-inducible factor prolyl hydroxylases. Roxadustat slightly increased renal Epo mRNA levels in healthy mice. Administration of (E)-THSG, a major constituent, significantly increased serum Epo levels. It is likely that (E)-THSG may facilitate the process to convert inactive renal Epo-producing cells to active Epo-producing cells. Collectively, it is implied that (E)-THSG in the EtOAc-soluble fraction of P. multiflorum roots may primarily improve blood deficiency of Kampo concept by promoting erythropoiesis.

Does Native Vitamin D Supplementation Have Pleiotropic Effects in Patients with End-Stage Kidney Disease? A Systematic Review of Randomized Trials.

Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host immunity. Vitamin D deficiency is common in patients with end-stage kidney disease (ESKD); however, current clinical practice has favored the use of the active hormone. Whether vitamin D deficiency should be corrected in patients with ESKD remains unclear, as few randomized trials have been conducted. In this systematic review, we summarize the current evidence examining whether vitamin D supplementation improves outcomes, beyond mineral metabolism, in patients with ESKD. Data from randomized controlled trials of adults with ESKD were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection from inception to February 2023. Twenty-three trials composed of 2489 participants were identified for inclusion. Data were synthesized by two independent reviewers and summarized in tables organized by outcome. Outcomes included measures of mortality, cardiovascular disease, inflammation, muscle strength/function, nutrition, patient well-being, and outcomes specific to ESKD including erythropoietin usage, pruritus, and dialysis access maturation. The Cochrane risk of Bias Tool (RoB 2, 2019) was used to assess study quality. Overall, our findings indicate a minimal and varied benefit of native vitamin D supplementation. From the largest studies included, we determine that vitamin D has no demonstrated effect on patient-reported measures of well-being or utilization of erythropoietin, nor does it change levels of the inflammation biomarker C-reactive protein. Included trials were heterogeneous with regards to outcomes, and the majority studied small participant populations with a relatively short follow-up. We conclude that vitamin D supplementation corrects vitamin D deficiency and is safe and well-tolerated in humans with ESKD. However, it is not clear from clinical trials conducted to date that a causal pathway exists between 25(OH)D and pleiotropic effects that is responsive to vitamin D treatment.

Anemia of inflammatory: does eiderr knowledge mean better diagnosis and treatment?

Anemia, which is a manifestation of the deterioration of patients' health and performance, is a common concomitant condition in diseases with signs of inflammation activation. This anemia - anemia of inflammation, is caused by disturbances of iron metabolism that lead to iron retention within macrophages, cytokine mediated inhibition of erythropoietin function and erythroid progenitor cell differentiation, and a reduced erytrocyte half-life. Anemia is usually mild to moderate, normocytic and normochromic. It is characterized by low iron circulation, but normal to increased levels of stored ferritin and the hormone hepcidin. The primary therapeutic approach is the treatment of the underlying inflammatory disease. In case of failure, iron supplementation and / or treatment with erythropoietin stimulating agents may be used. Blood transfusions are just an emergency treatment for life-threatening anemia. A new treatment modalities with hepcidin-modifying strategies and stabilizers of hypoxia inducible factors is emerging. However, their therapeutic efficacy needs to be verified and evaluated in clinical trials.

Investigation on the feasibility of large-volume autologous red blood cells donation: A pilot trial in a small cohort of Chinese.

BACKGROUND: Preoperative autologous blood donation (PAD) is used for elective surgical procedures with a predictable blood loss. But a downward trend in PAD is due to the fact that patients with preoperative whole blood donation or two-unit red cell apheresis cannot avoid receiving allogenic blood during intensive surgery. To improve the clinical application of PAD, this study explores the feasibility of large-volume autologous red blood cells (RBCs) donation by a pilot trial in a small cohort of Chinese. METHODS: This was a single-center, prospective study and 16 male volunteers were enrolled from May to October in 2020. Each volunteer donated 627.25 ± 109.74 mL (mean ± SD) RBC with apheresis machine or manually, and received 800 mg of intravenous iron in four divided doses. Blood pressure, oxygen saturation (SpO2 ), respiratory rate and heart rate were monitored throughout the procedure. The RBC count, hemoglobin (Hb) concentration, hematocrit (Hct), reticulocyte count, erythropoietin (Epo), serum iron, total iron binding capacity (TIBC), transferrin saturation, transferrin, and ferritin were dynamically detected and analyzed before and 8 weeks after blood donation. RESULTS: There was no differences in SpO2 , systolic and diastolic blood pressure before and after blood collection (P ≥ .05). The heart rate and respiratory rate after donation were slightly lower than those before (P < .05). The level of RBC, Hb concentration and Hct fell to a nadir on Day 3 (pre-donation vs post-donation on Day 3: RBC 4.81 ± 0.36*1012 /L vs 3.65 ± 0.31, P < .05; Hb 148.59 ± 11.92 g/L vs 113.19 ± 10.43 g/L, P < .05; Hct 44.08 ± 3.06% vs 33.38 ± 2.57%, P < .05) and recovered to the pre-donation levels at the eighth week post donation (pre-donation vs post-donation at the eighth week: RBC 4.81 ± 0.36*1012 /L vs 4.84 ± 0.34*1012 /L, P ≥ .05; Hb 148.59 ± 11.92 g/L vs 150.91 ± 11.75 g/L, P ≥ .05; Hct 44.08% ± 3.06% vs 43.86 ± 3.06%, P ≥ .05). Epo and the reticulocyte count reached the peak values on Days 1 and 7, respectively (Epo: D0 15.30 ± 7.47 mlU/ML vs D1 43.26 ± 10.52 mlU/ML, P < .05; reticulocyte count: D0 0.07 ± 0.02*109 /L vs D7 0.17 ± 0.04*109 /L, P < .05). The red cell net profits on Day 7, the second, fourth and eighth week postdonation were 160.39 ± 144.33 mL, 387.59 ± 128.74 mL, 530.95 ± 120.37 mL, and 614.18 ± 120.10 mL, and accounted for 27.47% ± 24.70%, 63.75% ± 24.91%, 86.20% ± 22.99%, and 99.20% ± 19.19% of RBC donation, respectively. The levels of serum iron, serum ferritin, and transferrin saturation increased during the first week because of the supplement of intravenous iron, and then gradually decreased and declined to the baseline at the end of the study period at the eighth week. CONCLUSIONS: The large-volume autologous RBCs donation of 600 mL is proved safe in our study. Combination support of normal saline to maintain blood volume and intravenous iron supplementation may ensure the safety and effectiveness of large-volume RBC apheresis.

Changes of biomarkers for erythropoiesis, iron metabolism, and FGF23 by supplementation with roxadustat in patients on hemodialysis.

This study aimed to confirm changes in biomarkers of erythropoiesis and iron metabolism and serum fibroblast growth factor 23 (FGF-23) during darbepoetin-α treatment and then switching to the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat. A total of 28 patients on hemodialysis who received weekly doses of darbepoetin-α were switched to roxadustat. Biomarkers for erythropoiesis and iron metabolism and intact and C-terminal FGF-23 were measured in blood samples collected before the HD session on days - 7 (darbepoetin-α injection), - 4, and - 2, and days 0 (switch to roxadustat treatment, three times weekly), 3, 5, 7, 14, 21, and 28. Erythropoietin and erythroferrone levels were elevated on day - 4 by darbepoetin-α injection and decreased to baseline levels at day 0. Levels of erythropoietin were not significantly increased by roxadustat supplementation, but erythroferrone levels were continuously elevated, similar to darbepoetin-α treatment. Hepcidin-25 and total iron binding capacity were significantly decreased or increased in patients treated with roxadustat compared with darbepoetin-α. Changes of intact and C-terminal FGF-23 levels were parallel to changes of phosphate levels during roxadustat treatment. However, the actual and percentage changes of intact FGF-23 and C-terminal FGF-23 in patients with low ferritin levels were greater than those in patients with high ferritin levels. Roxadustat might stimulate erythropoiesis by increasing iron usage through hepcidin-25, which was suppressed by erythroferrone in the physiological erythropoietin condition. Changes of intact FGF-23 and C-terminal FGF-23 levels might be affected by roxadustat in patients on hemodialysis, especially those with a low-iron condition.

Maintenance intravenous iron in hemodialysis patients to minimize erythropoietin doses: a double-blinded, randomized controlled trial (the MAINTAIN IRON trial).

In patients on chronic hemodialysis, there is no standard protocol for maintenance iron supplementation. This study aimed to compare two fixed-dose intravenous (IV) iron protocols to reduce erythropoiesis-stimulating agents (ESA). We conducted a double-blinded, randomized controlled study on hemodialysis patients having ferritin levels between 200 and 700 ng/dl and transferrin saturation values between 20 and 40%. Patients were assigned to receive either 100 or 200 mg of IV iron each month. ESA was adjusted every month to keep Hb between 10 and 12 g/dl. ESA dose at 12 months was the primary outcome. The secondary outcomes were all-cause mortality, cardiovascular events, absolute iron deficiency anemia (IDA), blood transfusion, adverse events, and iron withholding rate. Of the 79 eligible patients, 40 received 100 mg of IV iron, while 39 received 200 mg. At month 12, the mean monthly ESA dose in the 100-mg IV iron group was 35,706 ± 21,637 IU, compared to 26,382 ± 14,983 IU in the 200-mg group (P = 0.03). IDA was found in twelve patients (30%) in the 100-mg group and four patients (10.5%) in the 200-mg group (P = 0.05). In each group, three patients died (P = 0.9). Hospitalization, venous access thrombosis, and infection rates were similar in both groups. The withholding rate of IV iron was higher in 200-mg group (25% vs. 64.1%), but the protocol compliance was found more in 100-mg group (50% vs. 28.2%) (P = 0.001). In conclusion, monthly 200-mg IV iron infusions significantly reduce ESA doses but have a higher withholding rate. (Funded by the Kidney Foundation of Thailand and the Research Group in Nephrology and Renal Replacement Therapy from the Faculty of Medicine, Thammasat University).Thai Clinical Trials Registry number, TCTR20190707001.

Myelodysplastic Syndromes: New Methods of Diagnosis, Prognostication, and Treatment

BACKGROUND: Myelodysplastic syndromes (MDS) are malignant diseases arising from hematopoietic stem cells. Their overall incidence is 4 cases per 100 000 persons per year, and they are usually diagnosed when evaluating cytopenia. The median survival time is three years. Myelodysplastic syndromes take a variable course; one-quarter of patients go on to develop acute leukemia. METHODS: This review is based on publications retrieved by a selective search of the literature from 2013 to 2022, including relevant guidelines, in the PubMed database. The time period was chosen to reflect developments since the publication of the latest EHA guidelines in 2013. RESULTS: The gold standard of diagnosis is cytomorphology of the blood and bone marrow, supplemented by banding cytogenetics, histomorphology, and somatic mutation analyses. The new classification proposed by the WHO incorporates the molecular and cytogenetic findings. The Molecular International Prognostic Scoring System (IPSS-M), which takes somatic mutations into account, is now available as an aid to prognostication. Quality of life evaluation with standardized instruments is helpful in many ways. Low-risk patients are treated supportively with erythrocyte transfusions and iron chelation therapy. Erythropoietin-a can be given to patients whose erythropoietin level is less than 200ng/mL, lenalidomide to those with a 5q deletion, and luspatercept to those with an SF3B1 mutation. High-risk patients should be evaluated as early as possible for allogeneic hematopoietic stem cell transplantation with curative intent. 5-azacytidine improves outcomes in patients for whom stem cell transplantation is not suitable. CONCLUSION: Once a precise diagnosis has been established, new prognostic instruments such as the IPSS-M enable risk-adapted treatment based on the biological aspects of the patient's disease as well as his or her age and comorbidities.

Potential Interactions When Prescribing SGLT2 Inhibitors and Intravenous Iron in Combination in Heart Failure.

In patients with heart failure, sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to decrease hepcidin and ferritin and increase transferrin receptor protein, changes that are typically indicative of worsening absolute iron deficiency, as would be seen with poor dietary intake or gastrointestinal bleeding, neither of which is provoked by SGLT2 inhibitors. Therefore, 2 alternative conceptual frameworks may explain the observed pattern of changes in iron homeostasis proteins. According to the "cytosolic iron depletion hypothesis," the effect of SGLT2 inhibitors to decrease hepcidin and ferritin and increase transferrin receptor is related to a decline in cytosolic Fe2+ that occurs after drug-induced erythropoietin-related increase in iron use. Erythropoietin-mimetics (eg, darbepoietin) elicit this type of iron-deficiency pattern of response, and it is typically accompanied by erythropoietin resistance that is alleviated by intravenous iron supplementation. In contrast, according to the "cytosolic iron repletion hypothesis," the effect of SGLT2 inhibitors to decrease hepcidin and ferritin and increase transferrin receptor represents a direct action of these drugs: 1) to reverse inflammation-related increases in hepcidin and ferritin, and, thus, alleviate functional blocks on iron utilization; and 2) to increase in sirtuin-1 signaling, which suppresses hepcidin, accelerates the degradation of ferritin, and up-regulates transferrin receptor protein. Through either or both mechanisms, direct suppression of hepcidin and ferritin would be expected to increase cytosolic Fe2+, thus allowing an unattenuated erythrocytic response to erythropoietin without the need for intravenous iron supplementation. The totality of clinical evidence supports the "cytosolic iron repletion hypothesis" because SGLT2 inhibitors elicit a full and sustained erythrocytosis in response to erythropoietin, even in overtly iron-deficient patients and in the absence of intravenous iron therapy. Therefore, the emergence of an iron-deficiency pattern of response during SGLT2 inhibition does not reflect worsening iron stores that are in need of replenishment, but instead, represents potential alleviation of a state of inflammation-related functional iron deficiency that is commonly seen in patients with chronic heart failure. Treatment with intravenous iron may be unnecessary and theoretically deleterious.

The effects of postnatal erythropoietin and nano-erythropoietin on behavioral alterations by mediating K-Cl co-transporter 2 in the valproic acid-induced rat model of autism.

In this study, based on the excitatory/inhibitory imbalance theory of autism, the time window of GABA switch, the role of K-Cl co-transporter 2 (KCC2) in adjustment GABA switch, and brain permeability to erythropoietin (EPO), the effects of postnatal -EPO and- nano- erythropoietin (NEPO) have been evaluated in the valproic acid (VPA) rat model of autism. The VPA was administered for animal modeling of autism at gestational day (GD) 12.5 (600 mg/kg). Male offsprings were injected with EPO and NEPO in a clinically proper postnatal dosing regimen on postnatal days (PND) 1-5, and autistic-like behaviors were tested at the end of the first month. Then animals were sacrificed, and neuron morphology and KCC2 expression were examined by Nissl staining and Western blot. According to our findings, high-dose NEPO improved autism-associated phenotypes. Neuroprotective effects of EPO and NEPO have been shown in the hippocampus. Postnatal NEPO treatment reversed KCC2 expression abnormalities induced by prenatal VPA. Our results might support the role of KCC2 in ASD and the excitatory/inhibitory imbalance hypothesis. We suggested Nano- erythropoietin and other KCC2 interventions as a new approach to the early treatment and prevention of autism.

Neonatal Anemia.

All neonates experience a downtrend in their hematocrit values immediately following the birth through normal falls in erythropoietin (Epo) production, transition to adult hemoglobin, and hemodilution with somatic growth. However, this drop is more pronounced in critically ill and preterm neonates and can lead to potentially pathologic anemia that impairs tissue oxygen delivery. In this review, we highlight the mechanisms underlying physiologic anemia and anemia of prematurity and briefly review the evidence for the treatment of anemia in the neonatal population, including the use of red blood cell transfusions, erythropoietic stimulating agents, and iron supplementation.

Anemia after kidney transplantation.

Anemia is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence estimated between 20 and 80% depending on how defined. Causes of and risk factors for post-transplantation anemia (PTA) are multifactorial with iron deficiency being the primary cause of early PTA (within the first 6 months after transplantation) and impaired glomerular filtration rate (GFR) commonly responsible for late PTA (after 6 months). Medications, viral infections, chronic inflammation, and comorbidities also play a role. PTA has relevant long-term consequences and is a potential risk factor for allograft dysfunction, cardiovascular morbidity, and mortality. Thus, an anemia evaluation, approximately 3 months post-transplantation, is recommended in order to start early treatment and improve prognosis. Iron status, vitamin B12, folate, markers of hemolysis, and viral PCR should be checked, and medications, in particular combinations of medications, should be carefully evaluated. PTA treatment may be challenging and should be directed to the underlying causes. Iron supplementation and erythropoietin therapy, not extensively used in KTR, may be indicated. Every effort should be made to avoid blood transfusions in the pre-transplant period to avoid allosensitization. Anemia should be corrected to prepare candidates for kidney transplantation in order to reduce the need for perioperative blood transfusions as well.

Innovations thérapeutiques dans la prise en charge de l'anémie de la maladie rénale chronique Therapeutic innovations in the management of chronic kidney disease-associated anemia.

Anemia is a common complication of chronic kidney disease (CKD). The insufficient erythropoietin (EPO) production by the kidneys and iron deficiency are the main causes. Iron supplementation and the administration of recombinant EPO are the main treatment modalities. New iron formulations that can be administered orally, intravenously or directly via the dialysate have recently been developed to improve efficacy and tolerance. Ferric citrate administered orally can effectively corrects anemia in case of iron deficiency and in addition chelate phosphate in the gut lumen. Ferric carboxymaltose allows intravenous administration of larger doses given less frequently. Ferric pyrophosphate citrate administered directly via the dialysate allows the compensation of iron losses during the hemodialysis session. HIF-prolyl-hydroxylase inhibitors are a new therapeutic class of erythropoiesis-stimulating agents. Orally administered, they act by stabilizing the HIF transcription factor involved in the initiation of erythropoietin production by hypoxia. Several clinical studies have recently evaluated these new molecules in comparison with recombinant EPO. In CKD patients not yet on dialysis or undergoing dialysis therapy non-inferiority in correcting anemia has been demonstrated compared with recombinant EPO. The decrease in circulating hepcidin they induce appears greater than that induced by injectable recombinant EPO. Presently available reports on the safety of HIF-prolyl-hydroxylase inhibitors are reassuring but need to be confirmed in longer-term studies of larger size. © 2022 Published by Elsevier Masson SAS on behalf of Société francophone de néphrologie, dialyse et transplantation.

Reticulocyte hemoglobin content changes after treatment of anemia of prematurity.

BACKGROUND: Iron deficiency during infancy is associated with poor neurological development, but iron overload causes severe complications. Appropriate iron supplementation is therefore vital. Reticulocyte hemoglobin content (RET-He) provides a real-time assessment of iron status and chracterezes hemoglobin synthesis in preterm infants. However, the existing literature lacks detailed reports assessing chronological changes in RET-He. The aim of this study was to assess the chronological changes in RET-He during oral iron dietary supplementation, and concomitant therapy with recombinant human erythropoietin (rHuEPO) in preterm very low birthweight infants. METHODS: Very low birthweight infants, admitted to our neonatal intensive care unit were analyzed retrospectively. Hemoglobin (Hb), reticulocyte percentage (Ret), mean corpuscular volume, RET-He, serum iron (Fe), and serum ferritin were recorded. Data at birth (T0), the initial day of rHuEPO therapy (T1), the initial day of oral iron supplementation (T2), 1-2 weeks (T3), 3-4 weeks (T4), 5-6 weeks (T5), and 7-8 weeks (T6) from the initial day of oral iron supplementation were extracted, and their changes over time were examined. RESULTS: Reticulocyte hemoglobin content was highest at birth and declined rapidly thereafter, especially after starting rHuEPO therapy. There was no upward trend in RET-He after the initiation of oral iron supplementation, with a slower increase during 5-6 weeks after the initiation of iron therapy. CONCLUSIONS: During the treatment of anemia of prematurity, low RET-He levels may be prolonged. Anemia of prematurity should therefore be assessed and treated on a case-by-case basis, while considering the iron metabolic capacity of preterm infants.

Aluminum overload in the reverse osmosis dialysis era: does it exist?

BACKGROUND: Aluminum accumulation is a well-described complication in dialysis patients. Improvements in hemodialysis technology have possibly eliminated the occurrence of aluminum overload. Limited evidence suggests that aluminum overload may decline in the era of aluminum removal from dialysis fluids, even with the use of aluminum binders. METHODS: We examined the data from January 2014 to June 1, 2020, identified through our electronic records, to evaluate the desferrioxamine (DFO) test results for aluminum overload. The presentation and treatment of aluminum overload were recorded. RESULTS: Ninety-nine dialysis patients were enrolled for the DFO test. Forty-seven patients (47.5%) were identified as DFO test positive for aluminum overload, of which 14 (14/47) patients had symptoms, including one patient with an unexplained fracture, eight patients with unexplained anemia despite high-dose erythropoiesis-stimulating agents, and five patients with hypercalcemia (serum calcium >11 mg dL-1). None of the patients with aluminum overload developed encephalopathy. Only four of the 47 patients had microcytic anemia. Patients requiring longer treatments (>10 months versus <10 months) had similar basal serum aluminum (p = 0.219) but had an increase in serum aluminum after DFO (p = 0.041). Furthermore, the treatments decreased erythropoietin doses in the aluminum overload group, with serum total alkaline phosphatase levels <60 U L-1 (p = 0.028). CONCLUSION: We concluded that aluminum overload existed in the reverse osmosis dialysis era. In light of non-obvious symptoms, such as anemia and bone turnover change, serum aluminum in dialysis patients should be monitored in countries using aluminum-based phosphate binders, despite reverse osmosis dialysis.