Erythropoietin Deficiency Research Articles

Relationship between protein-energy wasting in adults with chronic hemodialysis and the response to treatment with erythropoietin

BackgroundIt is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO).MethodsRetrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the “Malnutrition Inflammation Score” (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value < 0.05 as statistically significant.ResultsSixty-one patients ended the follow up. Both groups were similar in basal hemoglobin, hematocrit and other hematopoiesis markers (p = NS). Patients without PEW have a decrease risk for poor response to treatment with EPO (RR = 0.562 [95% CI, 0.329–0.961-]) than those with PEW. Finally, hemoglobin concentrations were evaluated at baseline and every four weeks until week 12, finding a statistically significant improvement only in patients without PEW according MIS (p < 0.05).ConclusionsPEW is an incremental predictor of poor responsiveness to EPO in HD patients, thus, it is important to consider correcting malnutrition or wasting for a favorable response to treatment with EPO.

Hepcidin in hemodialysis patients and its association with anemia and serum iron indices

Introduction: Anemia is one of the most common complications in dialysis patients. Deficiency of erythropoietin is the most common cause of anemia in dialysis patients. Chronic kidney disease (CKD) patients have a negative iron balance. Hepcidin is an antibacterial peptide that its synthesis is controlled by the iron surface and inflammatory markers and plays an important role in iron hemostasis in hemodialysis patients. In the presence of anemia, the level of hepcidin in normal individuals is reduced. Therefore, the normal level of hepcidin in CKD individuals is considered high due to their anemia level, while, the level of hepcidin is reduced after dialysis. Objectives: We aimed to study the level of hepcidin-25 in hemodialysis patients and its relationship with anemia and serum iron indices. Patients and Methods: In a cross-sectional study, 70 patients who fulfilled inclusion criteria enrolled in the study. Serum hepcidin 25 was measured by ELISA method. At the same time, blood samples were taken to measure other indices including iron, ferritin, C-reactive protein (CRP), total iron binding capacity (TIBC) and albumin. Hepcidin-25 levels compared with other mentioned parameters. Statistical analysis was done in SPSS 18.0 software. Results: No significant relationship between inflammatory cytokines, TIBC and CRP and erythrocyte sedimentation rate (ESR) with hepcidin levels was detected. Additionally, relationship between serum iron, ferritin and hepcidin levels was not significant (P &gt; 0.05). Conclusion: Assessment of hepcidin 25 level for inflammation and iron status does not seem to be helpful for anemia management in hemodialysis patients.

Neurologic conditions and disorders of uremic syndrome of chronic kidney disease: presentations, causes, and treatment strategies

ABSTRACTIntroduction: Uremic syndrome of chronic kidney disease (CKD) is a term used to describe clinical, metabolic, and hormonal abnormalities associated with progressive kidney failure. It is a rapidly growing public health problem worldwide. Nervous system complications occur in every patient with uremic syndrome of CKD.Areas covered: This review summarized central and peripheral nervous system complications of uremic syndrome of CKD and their pathogenic mechanisms. They include cognitive deterioration, encephalopathy, seizures, asterixis, myoclonus, restless leg syndrome, central pontine myelinolysis, stroke, extrapyramidal movement disorders, neuropathies, and myopathy. Their pathogenic mechanisms are complex and multiple. They include (1) accumulation of uremic toxins resulting in neurotoxicity, blood–brain barrier injury, neuroinflammation, oxidative stress, apoptosis, brain neurotransmitters imbalance, ischemic/microvascular changes, and brain metabolism dysfunction (e.g. dopamine deficiency), (2) metabolic derangement (as acidosis, hypocalcemia, hyperphosphatemia, hypomagnesemia, and hyperkalemia); (3) secondary hyperparathyroidism, (4) erythropoietin and iron deficiency anemia, (5) thiamin, vitamin D, and other nutritional deficiencies, (6) hyperhomocysteinemia, and (7) coagulation problems.Expert commentary: Nervous system complications of uremia contribute to the patients’ morbidity and mortality. Optimizing renal replacement therapy, correction of associated metabolic and medical conditions, and improved understanding of possible pathogenic mechanisms of these complications is a major target for their prevention and treatment.

The Hepcidin-Anemia Axis: Pathogenesis of Anemia in Chronic Kidney Disease.

The pathogenesis of anemia in chronic kidney disease (CKD) could be multifactorial. In recent animal studies, hepcidin knockout (KO) mice with adenine-induced CKD did not exhibit anemia and iron deficiency. Hepcidin has emerged as a major player in the development of anemia in CKD. We suspected that erythropoietin (EPO) deficiency may not be the mainstay of anemia in CKD, although relative EPO deficiency could contribute to the failure to increase hemoglobin (Hb) levels. Some factors may interfere with the differentiation of erythroids. Based on previous flow cytometric analysis, the differentiation and maturation of bone marrow erythroid precursors were compared between 2 mouse models of anemia, namely, EPO-KO mice and adenine-induced CKD mice. EPO-KO mice exhibited greater than 50% reduction in the CD71-low/Ter119-high population, which represents a mature erythroid stage in the bone marrow. In contrast, these mice exhibited no reduction in the CD71-high/Ter119-low and CD71-high/Ter119-high cell populations, which represent an early erythroid stage. However, in CKD mice, the percentages of CD71-high/Ter119-low and CD71-high/Ter119-high erythroid cells, which correspond to proerythroblasts and basophilic erythroblasts, respectively, were decreased in bone marrow. Thus, the CKD mice exhibited a decrease in the number of cells expressing transferrin receptor 1 (TfR1) or early stage erythroblasts, which was completely different from the results obtained for EPO-KO mice. Thus, in CKD, decreased expression of TfR1 in erythroblasts as well as increased hepcidin levels in circulation may hamper erythroblast differentiation by decreasing the iron supply, as iron is an indispensable component of erythroblast differentiation. We conclude that deregulated iron metabolism could be the principal cause of anemia in CKD, impeding the differentiation of erythroblasts. We propose that the "hepcidin-anemia axis" is involved in the pathogenesis of CKD-associated anemia. For the treatment of anemia in CKD, declining hepcidin levels are essential for efficient erythropoiesis. Key Messages: These findings have led us to target the hepcidin-anemia axis as a new treatment strategy for anemia in CKD, including via newly developed erythropoiesis-stimulating agent and hypoxia inducible factor stabilizers.

Evaluasi terapi erytropoetin pada pasien hemodialisa di rumah sakit PKU Muhammadiyah Yogyakarta

Most of the patients with end-stage renal disease who undergo hemodialysis receive erythropoietin (EPO) therapy for anemia treatment. Anemia with EPO deficiency is a common complication of chronic kidney disease (CKD). EPO therapy is expected to improve anemia and quality of life of patients. This analytic observational study was conducted in a cross-sectional design. It aimed to identify the difference in red blood cell profiles, namely hemoglobin (Hb), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC), and quality of life of CKD patients on EPO and non-EPO therapy at PKU Muhammadiyah Hospital in Yogyakarta. The inclusion criteria were PGK ICD N18.9 outpatients who received hemodialysis therapy at this hospital and were literate, able to understand the questionnaire, and willing to be a respondent. The results showed that there was no significant difference (p>0,05) between the red blood cells (Hb, MCV, MCH, MCHC) of the EPO and non-EPO therapy groups. The correlation between the EPO and the quality of life of patients in all of the KDQOL domains was p> 0.05. Aside from the insignificant difference between the EPO and non-EPO therapy groups, the research concluded that there was no correlation between either the EPO or the non-EPO therapy with the quality of life of hemodialysis patients.

The deficiency of macrophage erythropoietin signaling contributes to delayed acute inflammation resolution in diet-induced obese mice

Obesity has been linked with altered acute inflammation resolution which contributes to obesity-related clinical complications; however, the mechanisms that contribute to obesity-related unresolved inflammation are not fully known. Here we demonstrated that the deficiency of macrophage erythropoietin (EPO) signaling contributed to delayed acute inflammation resolution in diet-induced obese mice. In zymosan-induced acute peritonitis, in line with the delayed resolution of inflammation, the induction of macrophage EPO signaling was significantly reduced in obese mice relative to normal mice. Exogenous EPO induced macrophage EPO signaling and promoted acute inflammation resolution in obese mice. Efferocytosis of apoptotic cells by macrophages which is central in inflammation resolution was impaired in obese mice and restored by exogenous EPO. Mechanistically, macrophage peroxisome proliferator-activated receptor-γ (PPARγ) was greatly reduced in obese mice and EPO increased macrophage PPARγ to promote efferocytosis in obese mice. Together, our results identify an important mechanism underlying aberrant acute inflammation resolution in obesity, with important implications for regulating unresolved acute inflammation and normalizing macrophage defects in obese and diabetic individuals.

Low 1,25-dihydroxyvitamin D level is associated with erythropoietin deficiency and endogenous erythropoietin resistance in patients with chronic kidney disease.

Erythropoietin (EPO) deficiency and resistance to endogenous EPO is an important pathophysiological feature in anemia of chronic kidney disease (CKD). Low 1,25 dihydroxyvitamin D [1,25(OH)2D] level is known to contribute to anemia of CKD. We aimed to investigate the associations between serum 1,25(OH)2D and anemia, EPO deficiency, and endogenous EPO resistance in patients with CKD. This study included 409 patients with CKD [glomerular filtration rate (GFR) < 60ml/min/1.73m2] who were not on dialysis therapy. Patients on exogenous EPO therapy and patients with iron deficiencies were excluded. Endogenous EPO resistance was assessed by calculating the ratio of endogenous EPO to hemoglobin (Hb) (endogenous EPO/Hb ratio). The associations of Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio with clinical and laboratory variables were investigated by univariate and multivariate analyses. In univariate analysis, serum 1,25(OH)2D level was correlated with the Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio. Multiple regression analysis revealed that the serum 1,25(OH)2D level remained significantly associated with the Hb level (β = 0.532, P < 0.001), endogenous EPO level (β = 0.149, P = 0.010), and the endogenous EPO/Hb ratio (β = - 0.187, P = 0.002), even after adjusting for other confounding factors, including the levels of parathyroid hormone and the inflammatory marker C-reactive protein. The serum 1,25(OH)2D level exhibited significant associations with anemia, EPO deficiency, and endogenous EPO resistance in CKD patients. These associations were independent of secondary hyperparathyroidism and inflammation status.

Therapeutic efficacy of erythropoietin alfa and erythropoietin beta in hemodialysis; a randomized controlled trial

Introduction: Anemia, as a common complication of end-stage renal disease (ESRD), usually develops due to erythropoietin deficiency. Recombinant human erythropoietins (rHEPOs) are indicated for the correction of renal anemia. Objectives: We aimed to evaluate the efficacy of a new brand of erythropoietin named CinnaPoietin (erythropoietin beta) on hemoglobin levels. Patients and Methods: This is a randomized double-blinded controlled trial. Ninety-six ESRD patients on hemodialysis recruited in the study, whose hemoglobin levels was less than 10 g/dL. They allocated to two groups. PDPoetin (erythropoietin alfa) 50-100 U/kg three times per week intravenously administrated to the control group and CinnaPoietin with exactly same regimen as like PDPoetin group administrated for the rest of the participants. The study duration was 3 months. We measured plasma hemoglobin monthly for 3 months. Results: We found, hemoglobin was increased across the time and it was statistically significant (P&lt;0.001), while there was no statistically significant differences between the groups (P=0.712). Conclusion: According to the result of the present study there is no statistical significant difference between these two brands of exogenous rHEPO in the case of increasing the hemoglobin concentration.

Neonatal anemia and transfusion

Anemia of neonate, especially in premature infants, is a common phenomenon in newborns and has attracted more and more attention in the academic world.There are various reasons for anemia.Besides the common pathophysiological basis such as iron deficiency and erythropoietin deficiency, blood group incompatibility, hemolysis and iatrogenic blood loss are also important factors leading to anemia of neonates.Preventive measures for neonatal anemia include delayed ligation of the umbilical cord, the application of erythropoietin and the effective reduction of iatrogenic blood loss.At present, blood transfusion is still one of the main treatments for neonatal anemia.However, there are still controversies about transfusion indications as well as it′s short-term and long-term side effects. Key words: Infant, newborn; Anemia; Transfusion

Erythropoietic Response to Anaemia of Dialysis Naïve Patients with Chronic Kidney Disease in Zaria, North-West Nigeria.

Chronic kidney disease (CKD) is a global health problem with an increasing prevalence worldwide. Anemia is one of its consistent and severe hematological complications although its mechanism is not fully elucidated. The primary defect could manifest as serum erythropoietin (sEPO) deficiency or EPO resistance. We set out to determine the erythropoietic response to anemia of patients with CKD and its relationship with their iron status in a cross-sectional descriptive study of 91 patients in various stages of CKD. Materials and Methods: Soluble transferrin receptor (sTfR), sEpo, and serum ferritin levels were determined using ELISA method (Diagnostic Automation Inc and WKEA med supplies corp.). Data generated were analyzed using Epi Info version 3.5.3 and level of statistical significance was set at ≤0.05. Results: Participants comprised of 50 females (54.9%) and 41 (45.1%) males with an overall mean age of 47 ± 15 years. The major causes of CKD were hypertension (HTN) (50.54%), diabetes mellitus (DM) (6.59%), and HTN + DM (19.78%). The mean hemoglobin (Hb) concentration of the participants was 10.97 ± 2.28 g/dl; the red cell indices were within normal ranges except for Red cell distribution width-Coefficient of variation (%) which was elevated (16.29%). The mean serum ferritin, sTfR, and sEpo were 70.58 ± 46.44 ng/ml (interquartile range [IQR] 82.00), 22.9 ± 49.7 ng/ml (IQR 15.00), and 12.49 ± 33.47 IU/L (IQR 6.00), respectively, with a high variance. Serum ferritin and sTfR are consistently low across the stages of CKD (range between 54.54 ng/ml and 88.64 ng/ml), but sEPO for stage 3 and 4 showed a 2-fold increase when compared to normal level at Hb 10.97 g/dl (29.54 IU/L and 38.83 IU/L, respectively). Correlation between sTfR and sEpo (r2 = 0.96, P = 0.001), while between sEpo and serum ferritin (r2 = 0.02, P = 0.185), and between Hb and stage of CKD undulating (r2 = 0.41, P = 0.001). In contrast to some existing literature, this study has demonstrated that EPO resistance and iron deficiency contributes to anemia in CKD and serum ferritin can be used to assess the iron level of dialysis naïve CKD patients at every stage of the disease.

Red cell alloimmunization in multitransfused chronic renal patients on haemodialysis in a tertiary care centre of Jammu region

Background: There is a high incidence of alloimunization in many patients with diseases that require repetitive blood transfusions. One such group is chronic renal failure patients as majority of them have severe anemia due to deficiency of erythropoietin. As many such patients are unable to afford erythropoietin, they are treated with blood transfusions. This study was thus undertaken to study alloimunization in such patients at our center.Methods: A total of 96 patients found eligible were enrolled in this cross-sectional study that was carried out from June 2016 to august 2016. After detailed history, antibody screening was done by using Immucor Panoscreen three vial set and if screening came out to be positive antibody identification was then done by using Immucor Panocell-10.Results: 96 patients including 76 male and 20 female patients recieved a total of 912 transfusions. Alloantibodies were detected in a total of 12 patients (12.5%). Of these 12 patients 8 patients had a single antibody whereas 4 patients developed two antibodies. The antibodies developed at a rate of 1.8% per transfusion (16/912). On alloantibody type identification, the most common type found was anti E (4/16) followed by both anti D and anti C in 3 patients each.Conclusions: Alloimmunization to minor erythrocyte antigens occurs in many patients of chronic renal failure. This results in frequent pre-and post-transfusion complications. Inclusion of antibody screening test in routine pretransfusion testing protocol for the patients who are at higher risk of alloimmunization and require long-term transfusion dependence is desirable.

Epoetin alfa resistance in hemodialysis patients with chronic kidney disease: a longitudinal study.

Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.

Renal anemia and hydration status in non-dialysis chronic kidney disease: Is there a link?

Rationale: Anemia, a common feature in chronic kidney disease (CKD), has multiple contributors to its pathogenesis. Besides the well recognized erythropoietin and iron deficiencies, hydration status might be involved.Objective: To assess the prevalence and correlations of anemia, iron deficiency and overhydration in patients with stage 2 to 5 CKD.Methods and Results: This cross-sectional study enrolled 125 erythropoietin and iron therapy naïve non-dialysis CKD patients, without a identifiable cause of anemia.Parameters of hematological, iron, inflammatory and nutritional status were measured. The overhydration parameter (OH) assessed by bioimpedance spectroscopy was used to characterize hydration status.The prevalence of decreased hemoglobin (Hb) <110g/L increased along CKD stages from 0% to 40% (p=0.008). Fluid overload (OH >1L) and lower serum albumin (<40g/L) were more common in stage 5 versus stage 3 CKD (53% vs. 10%, p<0.001, and 27% vs. 3%, p=0.02, respectively), suggesting a potential dilutional reduction in serum proteins. Conversely, decreased iron stores (ferritin <100mcg/L) and iron availability (transferrin saturation, TSAT<0.20) were similarly prevalent irrespective of kidney function decline.Hemoglobin was positively correlated with estimated glomerular filtration rate (eGFR), serum albumin, and transferrin saturation, but inversely with OH. However, in a model of multiple linear regression which explained 32% of hemoglobin variation, only eGFR and overhydration remained the independent predictors of anemia.Discussion: As fluid overload is a common denominator for hemoglobin and TSAT levels, and is closely related to the declining kidney function, it should be considered in the management of renal anemia, at least in advanced CKD.

Treatment of renal anemia: Erythropoiesis stimulating agents and beyond.

Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10–11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

La Sindrome Anemica Cardio-Renale. Prima Parte: Epidemiologia e Aspetti Clinici

Abstract non disponibile (Cardionephrology)

Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence anemia parameters in hemodialysis patients

BackgroundThe main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) -three protein bound uremic toxins- are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients.MethodsBetween June and July 2014, we conducted an observational cross sectional study in two hemodialysis center. Three statistical approaches were conducted. First, we compared patients treated with ESA and those not treated. Second, we performed linear regression models between IAA, IS, and PCS plasma concentrations and hemoglobin, the ESA dose over hemoglobin ratio (ESA/Hemoglobin) or the ESA resistance index (ERI). Third, we used a polytomous logistic regression model to compare groups of patients with no/low/high ESA dose and low/high hemoglobin statuses.ResultsOverall, 240 patients were included in the study. Mean age ± SD was 67.6 ± 16.0 years, 55.4% were men and 42.5% had diabetes mellitus.When compared with ESA treated patients, patients with no ESA had higher hemoglobin (mean 11.4 ± 1.1 versus 10.6 ± 1.2 g/dL; p <0.001), higher transferrin saturation (TSAT, 31.1 ± 16.3% versus 23.1 ± 11.5%; p < 0.001), less frequently an IV iron prescription (52.1 versus 65.7%, p = 0.04) and were more frequently treated with hemodiafiltration (53.5 versus 36.7%). In univariate analysis, IAA, IS or PCS plasma concentrations did not differ between the two groups.In the linear model, IAA plasma concentration was not associated with hemoglobin, but was negatively associated with ESA/Hb (p = 0.02; R = 0.18) and with the ERI (p = 0.03; R = 0.17). IS was associated with none of the three anemia parameters. PCS was positively associated with hemoglobin (p = 0.03; R = 0.14), but negatively with ESA/Hb (p = 0.03; R = 0.17) and the ERI (p = 0.02; R = 0.19). In multivariate analysis, the association of IAA concentration with ESA/Hb or ERI was not statistically significant, neither was the association of PCS with ESA/Hb or ERI. Identically, in the subgroup of 76 patients with no inflammation (CRP <5 mg/L) and no iron deficiency (TSAT >20%) linear regression between IAA, IS or PCS and any anemia parameter did not reach significance.In the third model, univariate analysis showed no intergroup significant differences for IAA and IS. Regarding PCS, the Low Hb/High ESA group had lower concentrations. However, when we compared PCS with the other significant characteristics of the five groups to the Low Hb/high ESA (our reference group), the polytomous logistic regression model didn’t show any significant difference for PCS.ConclusionsIn our study, using three different statistical models, we were unable to show any correlation between IAA, IS and PCS plasmatic concentrations and any anemia parameter in hemodialysis patients. Indolic uremic toxins and PCS have no or a very low effect on anemia parameters.

Increased ventilation in female erythropoietin-deficient mouse line is not progesterone and estrous stage-dependent

Previous studies suggest that chronic erythropoietin (Epo) deficiency in male mice does not alter normoxic/hypoxic ventilation. As effects of Epo are sex specific and as progesterone could be a respiratory stimulant, we evaluated the impact of Epo deficiency and its possible interaction with progesterone in ventilatory control in female mice during estrous cycle phases. Compared to wild type (WT) animals, Epo-TAgh female mice exhibited higher ventilation in hypoxia. However, when data were separated into luteal and follicular phases of the estrous cycle, basal ventilation and hypoxic ventilation were not different in both mice strains. As progesterone is known to be a potent respiratory stimulant, additional experiments were performed to elucidate its role. Interestingly, after mifepristone treatment, HVR was not modified in WT and Epo-TAgh mice, showing that the ventilatory stimulation observed in females was not directly mediated by progesterone. We conclude that Epo-TAgh female mice show no estrous stage-dependent increase of ventilatory control and progesterone independent response to hypoxia.

Role of Hepcidin-25 in Chronic Kidney Disease: Anemia and Beyond.

Iron is an essential element for all living organisms, but produces toxic oxidants. Thus, iron homeostasis is tightly regulated in mammals. Hepcidin-25 (hepcidin) has emerged as a molecule that regulates iron metabolism. Binding of hepcidin to its receptor, ferroportin, inhibits intestinal iron absorption and iron efflux from hepatocytes and macrophages. Decreased hepcidin enhances iron absorption and efflux. Hepcidin could be predictive of iron status and the response to iron supplementation or erythropoietin-stimulating agents. Monitoring hepcidin is helpful for the management of anemia. Thus, it is urgent to obtain normal reference values in a large population of healthy subjects and to standardize various hepcidin assays, which enables to compare the data measured by different methods. Anemia is an important and common problem associated with chronic kidney disease (CKD), which is caused by erythropoietin deficiency, iron-restricted erythropoiesis, inflammation, hypoxia, vitamin D deficiency, hyperparathyroidism, and obesity. Anemia causes poor quality of life, progression of CKD, increased risk of cardiovascular events, and mortality. Besides its role in anemia, recent evidence suggests that hepcidin-25 plays a role in the pathogenesis and progression of kidney injury via modulation of iron-mediated oxidant injury. Despite accumulating experimental data, information about clinical significance of hepcidin-25 for anemia and kidney injury in CKD patients is scarce, especially in children. This review summarizes the current knowledge of the role of hepcidin-25 in the regulation of anemia and kidney injury in children and adults with CKD. Strategy for modulating hepcidin-25 to prevent anemia and kidney injury associated with CKD is also discussed.

Prevalence and predictors of anaemia among patients presenting with kidney diseases at the University of Dodoma Hospital in central Tanzania

Background: Anaemia is a common complication that contributes to the burden of kidney diseases. Anaemia confers significant risk of cardiovascular disease and contributes to decreased quality of life. While the primary cause of anaemia is the inadequate production of erythropoietin by the kidneys to support erythropoiesis, other factors may contribute to anaemia. The aim of this study was to determine the prevalence and predictors of anaemia among patients presenting with kidney diseases at the haemodialysis unit of the University of Dodoma (UDOM) hospital in central Tanzania.Methodology: In this retrospective study we reviewed data of patients who presented at UDOM haemodialysis unit in Tanzania with kidney diseases as from January 2013 to June 2015. Data were descriptively and inferentially analysed using Stata version 11 software.Results: A total of 1,395 patients were involved in this study. Of these, 792 (56.8%) presented with kidney diseases, 249 (31.4%) were found to have anaemia. The leading cause of anaemia was chronic kidney disease (CKD) 136 (54.6%), blood loss 74(29.7), haemolysis 15 (6.0%), Nutrition 13(5.2%) and others 11 (4.4%). Glomerular filtration rate of &lt; 60 mL/min/1.73 m2 accounted for 59.1% of CKD. Median [IQR] serum creatinine level: 246 [177 – 317] μmol/L, Urea level 16[8 -24] mmol/L and haemoglobin of 9.8 [6.2 - 13.4] g/dL. Prevalence of anaemia was strongly associated with declining glomerular filtration rate (P= 0.01).Conclusion: Anaemia is very common among patients presenting with kidney diseases. These patients require a thorough evaluation to identify and correct causes of anaemia other than erythropoietin deficiency.

Quel pourrait être le futur de la prise en charge de l’anémie dans l’insuffisance rénale chronique ?

Erythropoietin (EPO) plays an essential role in the regulation of erythropoiesis. Its production is under the control of the Hypoxia Inducible Factor (HIF) protein whose stability varies according to the oxygen level. During chronic renal failure, EPO deficiency is the main cause of anemia, but other factors such as iron deficiency and inflammatory syndrome are also involved. More recently, it is hypothesized that other factors such an excess of GDF-11 production may be also involved. Thus, beside Epo treatment HIF and GDF-11 are potentially new therapeutic targets in anemia of chronic kidney disease.