Anemia Of Chronic Renal Failure Research Articles

Effect of Near-Infrared Blood Photobiomodulation on Red Blood Cell Damage from the Extracorporeal Circuit during Hemodialysis In Vitro

The contact of blood with the bioincompatible membranes of the dialyzer, which is part of the extracorporeal circuit during hemodialysis (HD), causes upregulation of various cellular and non-cellular processes, including massive generation and release of reactive oxygen species (ROS), (which is one of the primary causes of anemia in chronic renal failure). We hypothesize that near-infrared (NIR) radiation possesses antioxidant properties and is considered to protect the red blood cell (RBC) membrane by enhancing its resilience to negative pressures. Our experimental setup consisted of an HD machine equipped with a dialyzer with a polyamide membrane; whole bovine blood was examined in vitro in blood-treated circulation. Blood samples were taken at 0, 5, 15, and 30 min during the HD therapy. We also assessed osmotic fragility, hematocrit, hemolysis, and oxidative stress as a concentration of reactive thiobarbituric acid substances (TBARS). Our results have shown that RBC membrane peroxidation increased significantly after 30 min of circulation, whereas the TBARS level in NIR-treated blood remained relatively steady throughout the experiment. The osmotic fragility of NIR-irradiated samples during dialysis was decreased compared to control samples. Our studies confirm that in vitro, blood photobiomodulation using NIR light diminishes oxidative damage during HD and can be considered a simultaneous pretreatment strategy for HD.

A multicentre, multi-national, double-blind, randomised, active-controlled, parallel-group clinical study to assess the safety and efficacy of PDA10 (Epoetin-Alfa) vs. Eprex\xae in patients with anaemia of chronic renal failure

BackgroundErythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management.ObjectiveTo determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®.MethodsA phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase.ResultsThe PDA10 and Eprex® were shown to be therapeutically equivalent (p < 0.0001) with mean absolute change in haemoglobin from baseline of − 0.176 (± 0.91) g/dl and − 0.118 (± 1.114) g/dl, respectively. Weekly dose change was 10.01 IU/kg/week in PDA10 group and 10.30 IU/kg/week in Eprex® group, which has no significant difference. There were no significant differences in the safety profile between PDA10 and Eprex® groups.ConclusionThis study has confirmed the therapeutic equivalence between PDA10 and Eprex® in terms of efficacy, dosage requirement and safety profile in haemodialysis patients with renal anaemia.Trial registrationThe study was registered with the National Medical Research Register (NMRR-13-400-16313). This study has been registered retrospectively with Clinical Research Information Service (CRiS), Republic of Korea on 25 March 2021.

Erythropoietin and the Role of Inflammation in Anaemia in Patients with Chronic Renal Living in Cote D’ivoire

Introduction: Anemia is one of the most common complications of kidney failure. The kidney is responsible for the production of erythropoietin, a key hormone in erythropoiesis. Insufficient production of erythropoietin due to impaired kidney functions and also inflammation could explain this anemia. This study aimed at contributing to a better understanding of the mechanisms of erythropoietin in anemia observed in kidney failure.&#x0D; Methods: The study population consisted of 138 people: 92 with chronic renal failure (46 not on dialysis, 46 on hemodialysis) and 46 voluntaries as control without kidney failure. Serum concentrations of urea, creatinine, C-reactive protein (CRP), serum iron, ferritin and transferrin were determined using the Cobas C311 Hitachi machine. The erythropoietin assay was performed on the ELISA chain.&#x0D; Results: Lower mean values ​​of EPO, increased CRP and decreased iron were observed in CKF patients (EPO: 5.66 ± 0.97 mIU / L; CRP: 45 ± 7.46 mg / l ; Iron: 12.46 ± 0.85 µmol / l), and patients under dialysis (EPO: 9 ± 0.51 mIU / L; CRP: 9 ± 2.66 mg / l; Iron: 10.07 ± 0.54 µmol / l) compared to controls (EPO: 18 ± 1.29 mIU / L; CRP: 2 ± 0.30 mg / l; Iron: 15.85 ± 0.56 µmol / l).&#x0D; Conclusion: Anemia in chronic renal failure is thought to be due to an erythropoietin deficiency but also to an exacerbation of inflammation with a disruption of the iron status.

Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV.

ABSTRACTBackgrounds:Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores.Method:To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP.Results:Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C.Conclusions:Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

2343-PUB: Reduction of HbA1c after SGLT2 Inhibitors Correlate with Change in Plasma Osmolarity but Not with Elevation of Hematocrit in Japanese Patients with Type 2 Diabetes

Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors is expected its hematopoietic effect for treatment of the anemia in chronic renal failure. However, it is still unclear whether the effect is independent from its antidiabetic effect. In this study, we investigated correlations between hematocrit elevation, HbA1c reduction or parameters reflecting diuretic change in patients with type 2 diabetes (T2D). A total of 46 patients (male: n = 33, age: 54.6 ± 10.4 [mean ± SD] years, BMI: 29.2 ± 4.3 kg/m2, HbA1c: 8.7 ± 1.0%) with T2D who were newly administered SGLT2 inhibitors from July 2014 to November 2016 were retrospectively identified. The patients with HbA1c less than 7.0% at the baseline or who showed decrease in hematocrit or increase in HbA1c were excluded. Changes in HbA1c, hematocrit, urine specific gravity, uric acid, serum creatinine and plasma osmolarity levels between before and 30 days after the administration of the drugs were evaluated. Plasma osmolarity was calculated by the formula (2 x (Na [mEq/l] + K [mEq/l])) + (BUN [mg/dl]/2.8) + (glucose [mg/dl]/18). HbA1c was decreased (-0.68 ± 0.50%; p = 0.001) and hematocrit (2.1 ± 1.4%; p = 0.002) and urine specific gravity (0.008 ± 0.009 g/ml; p &amp;lt; 0.001) were increased significantly. However, uric acid, serum creatinine and plasma osmolarity did not show change. Changes in HbA1c and plasma osmolarity showed significant correlation (r = -0.31; p = 0.03) whereas changes in hematocrit and plasma osmolarity did not (r = -0.01; p = 0.94). HbA1c showed no significant correlation with hematocrit, serum creatinine, uric acid or urine specific gravity; hematocrit also did not have significant correlation with serum creatinine, uric acid or urine specific gravity. In conclusion, our data suggest that the elevation of hematocrit and decrease in HbA1c after the administration of SGLT2 inhibitors have different relation with parameters reflecting diuretic effects. Disclosure Y. Wada: None. Y. Hamamoto: Speaker’s Bureau; Self; Novo Nordisk A/S. Y. Nakatani: None. J. Fujikawa: None. Y. Iwasaki: None. S. Yoshiji: None. M. Aizawa-Abe: None. K. Iwasaki: None. S. Honjo: None. A. Hamasaki: None.

Evaluation of hepcidin level in chronic hepatitis C Egyptian patients undergoing regular hemodialysis

BackgroundHepcidin, an acute phase reactant released from the liver, suppresses intestinal iron uptake and release from internal stores. It is related to pathogenesis of anemia of chronic illness including anemia of chronic renal failure which is considered a chronic inflammatory state as well as HCV infection. The main purpose of this study is to evaluate level of serum hepcidin and study the possible relations between serum hepcidin and markers of iron status in chronic hepatitis C Egyptian patients on regular hemodialysis.ResultsHepcidin was significantly elevated in hemodialysis patients than in control group [P < 0.01]. Levels of hemoglobin, hematocrit, ferritin, and iron were significantly elevated in HCV-positive hemodialysis patients than in HCV-negative hemodialysis patients [P < 0.001]. Hepcidin was non-significantly elevated in HCV-positive hemodialysis patients compared with HCV-negative hemodialysis patients. No significant correlations between hepcidin and any of the other studied parameters.ConclusionSerum hepcidin is elevated in hemodialysis patients than in control group, whereas hepcidin level is non-significantly elevated in HCV-positive hemodialysis patients compared with HCV-negative hemodialysis patients.

Aetiological and Clinical Pattern of Severe Anaemia in a Tertiary Care Hospital at Rajshahi, Bangladesh

Background: Anaemia is a common health problem encountered in our day to day medical practice. It occurs in every age groups, in both sexes in every communities and all countries.Objective: To find out the aetiological pattern and clinical profile of severe anaemia for prompt diagnosis an droper management.Materials and Methods: The prospective study was carried out in different Medicine unit at Rajshahi Medical College Hospital (RMCH), Rajshahi on consecutive 100 hospital admitted patients having severe anaemia. All underwent routine and some special investigations for severe anaemia.Results: Peak age incidence was 20-29 years (38%) and sex incidence was male (68%). Most of the patients were farmers (38%). Common monthly income group was &gt;2000-5000 (48%). Incidence of severe anaemia was aplastic (26%), leukaemia (24%), haemolytic (22%), anaemia of chronic disorder (10%), iron deficiency anaemia (9%) and anaemia of chronic renal failure (9%). Peak age incidence for aplastic anaemia was 20- 29 years (42.3%), for leukaemia 14-19 years 33.3%), for haemolytic anaemia 14-19 years (50%), for anaemia of chronic disorder 20-29 and 30-39 years (30% each), iron deficiency anaemia 40-49 years (44.5%) and for anaemia of chronic renal failure 30-39 years (33.3%).Conclusion: Multicentre study with large sample size is warrented to develop more insights about diagnosis and management of severe anaemia.KYAMC Journal Vol. 6, No.-2, Jan 2016, Page 631-636

Anemia in children with chronic renal failure Special attention erythrocyte indices and iron deficiency anemia

Background Anemia in chronic renal failure (CRF) has beenproved to influence the quality of life, increasing morbidity andmortality. Early diagnosis and prompt treatments of anemia aremandatory to manage CRF appopriately. So far data of anemia inCRF in Indonesia is limited.Objective To find out the profile of anemia in children with CRF atCipto Mangunkusumo Hospital (CMH), Jakarta, with special atten-tion in erythrocyte indices and iron deficiency anemia.Methods Cross-sectional descriptive study was carried out onpatients with CRF and anemia in CMH since October 2003 to April2004.Results There were 20 CRF patients, aged between 1 year 3 month-15 year old, mostly were above 10 year old, 11 patients were malesand 9 were females. The most frequent etiologies were urinarytract infection (UTI) in 10 cases and nephrotic syndrome in 6 cases.Of those 20 patients, 14 suffered from anemia with erythrocyteindices, normochrome normocytic in 9 patients and hypochromemicrocytic in 5 patients. Of 14 anemic patients only 1 patient suf-fered from iron deficiency anemia of less than 10 mg/l and transferinsaturation of less than 12%. Based on serum iron (SI) concentra-tion only, 7 patients were diagnosed as having iron deficiency ane-mia.Conclusion Most patients with chronic renal failure havenormochrome normocytic anemia. Hypochromic microcytic irondeficiency anemia is scarcely found in this group of patients.

Effects of amino acids and albumin on erythropoietin carbamoylation

Anemia in chronic renal failure results from inadequate production of erythropoietin and decrease in its biological activity, and the reduced activity of erythropoietin is caused by the presence of plasma inhibitors of erythropoietin. It is reported that one of the inhibitors of erythropoietin is cyanate, a potential uremic toxin formed spontaneously from increased urea due to decreased renal function, and erythropoietin loses its biological activity due to negatively charged cyanate. The purpose of this study is to investigate the protective effects of amino acids, positively charged amino groups, and albumin binding of several toxins on erythropoietin carbamoylation. The degree of change in erythropoietin structure by cyanate was measured by the trinitrobenzenesulphonate reaction and Western blotting. The loss of biological activity of erythropoietin caused by cyanate was measured by injecting erythropoietin into rats with chronic renal failure. The free amino groups in erythropoietin decreased under cyanate treatment in a time- and concentration-dependent manner. In the cyanate treatment group, of the twenty amino acids, phenylalanine, valine, tryptophan, threonine, and lysine prevented the structural modification of erythropoietin, according to Western blot analysis. In addition, of the three proteins, albumin prevented the structural modification of erythropoietin. As for the cyanate with erythropoietin treatment group, only lysine and albumin prevented the loss of biological activity of erythropoietin in the rats. The results of this study suggest that lysine and albumin may play a protective role against renal anemia by erythropoietin carbamoylation in chronic renal failure.

Particularities of anaemia in framework of systemic lupus erythematosus

chronic disease (ACD) n = 34 (57.6%), iron deficiency anemia (IDA) n = 20 (33.9%), autoimmune hemolytic anemia (AHA) n = 3 (5.1%) and other forms (anaemia of chronic renal failure) causes n = 2 (3.4%). Leucopenia was present at 18 (30.5%) patients, limphopenia at 19 (32.2%) patients and thrombocitopenia at 13 (22.0%) patients. Assessment of disease activity by SLAM showed that low disease activity was determined in 12 (20.3%) patients, moderate activity was found in 36 (61.0%) and high activity - in only 11 (18.6%) patients. This demonstrated that in examined patients was predominant moderate activity 61.0% cases and ACD 57.6%. Conclusions Anaemia is a common manifestation in SLE and it is closely associated with moderate disease activity. These associations are observed after one year of evolution of systemic lupus erythematosus. Different levels of anaemia may be used to monitor the disease activity.

Serum prohepcidin level in myelodysplasia

This study highlights the iron profile of myelodysplastic patients in the era of hepcidin and its pro-hormone, pro-hepcidin. Previous studies have focused on the anemia of chronic renal failure, thalassemia, and hemochromatosis. We determined if pro-hepcidin played a role in iron overload in patients with myelodysplasia (MDS). Thirty adult patients with MDS and 20 healthy adults (controls) were selected. Our results revealed a statistically significant difference in pro-hepcidin levels between the two tested groups (Z = 2.9, p = 0.003). There was a weak positive correlation between pro-hepcidin and hematocrit (HCT; r = 0.49, p = 0.02) in the healthy group only. Neither age, subtypes of MDS, gender, soluble transferrin receptor (sTFR) or ferritin affected the pro-hepcidin level in patients with MDS. The role of ineffective erythropoiesis in the regulation of pro-hepcidin is superior to the role of chronic blood transfusion therapy.

Rx report

Rx report

Erythropoïétine: Quand la prescrire? Pourquoi et comment la doser?

Erythropoietin (EPO) is the principal haematopoietic growth factor of the red blood cell line. Its major role is to stimulate the red blood cell production. EPO synthesis by peritubular cells in the kidney is regulated by oxygen concentration and must lead adaptation of the organism to face many different physiological situations. An imbalance can lead either to anaemia or polycythemia. Synthetic EPO, so-called recombinant, has definitively changed the treatment in the anaemia of chronic renal failure and regularly find new indications, legal (anaemia of cancer, anaemia of chronic inflammatory syndromes, myelodysplastic syndromes, neurology, cardiology...) or illegal (doping substance in sport). This article reviews the physiology, the role and the indications of EPO in clinical routine practice and define why and how EPO should be measured. We also focus on the analytical requirements for serum EPO concentration determination, especially in the differential diagnosis of polycythemias (secondary polycythemia/Polycythemia Vera).

RNA Interference-Mediated Inhibition of Erythropoietin Receptor Expression Suppresses Tumor Growth and Invasiveness in A2780 Human Ovarian Carcinoma Cells

Although recombinant human erythropoietin (rHuEpo) has revolutionized the treatment of anemia, recent clinical trials suggested that rHuEpo use may be associated with decreased survival in cancer patients. Although the expression of erythropoietin (Epo) receptor (EpoR) has been demonstrated in various human cancers, the effect of exogenous Epo on the growth and therapy resistance of EpoR-bearing tumor cells is unclear at present. In the current study, we examined the hypothesis that EpoR may contribute to tumor growth independent of Epo in A2780 human ovarian carcinoma cells. A2780 human ovarian carcinoma cells showed high levels of EpoR expression, but lacked expression of Epo mRNA and biologically active Epo protein under both normoxic and hypoxic conditions. Exogenous Epo did not stimulate EpoR-mediated signaling, proliferation, invasiveness, or resistance to cytotoxic drugs in A2780 cells. In contrast, specific inhibition of EpoR expression using a short hairpin RNA (shRNA) expression plasmid resulted in markedly reduced proliferation and invasiveness in vitro. In addition, inhibition of EpoR expression led to abrogated in vivo ovarian cancer cell growth in a tumor xenograft system and resulted in decreased EpoR signaling. Our findings suggest that EpoR may be constitutively active in some cancer cells in the absence of Epo and provide the first evidence for a potential role of an Epo-independent, EpoR-mediated pathway in the growth of some human cancers.

Use of agents stimulating erythropoiesis in digestive diseases

Anemia is the most common complication of inflammatory bowel disease (IBD). Control and inadequate treatment leads to a worse quality of life and increased morbidity and hospitalization. Blood loss, and to a lesser extent, malabsorption of iron are the main causes of iron deficiency in IBD. There is also a variable component of anemia related to chronic inflammation. The anemia of chronic renal failure has been treated for many years with recombinant human erythropoietin (rHuEPO), which significantly improves quality of life and survival. Subsequently, rHuEPO has been used progressively in other conditions that occur with anemia of chronic processes such as cancer, rheumatoid arthritis or IBD, and anemia associated with the treatment of hepatitis C virus. Erythropoietic agents complete the range of available therapeutic options for treatment of anemia associated with IBD, which begins by treating the basis of the inflammatory disease, along with intravenous iron therapy as first choice. In cases of resistance to treatment with iron, combined therapy with erythropoietic agents aims to achieve near-normal levels of hemoglobin/hematocrit (11-12 g/dL). New formulations of intravenous iron (iron carboxymaltose) and the new generation of erythropoietic agents (darbepoetin and continuous erythropoietin receptor activator) will allow better dosing with the same efficacy and safety.

Randomized Study of Darbepoetin Alfa and Recombinant Human Erythropoietin for Treatment of Renal Anemia in Chronic Renal Failure Patients Receiving Peritoneal Dialysis

Darbepoetin alfa can be administered less frequently than recombinant human erythropoietin (r-HuEPO) for the treatment of anemia in chronic renal failure (CRF) patients. We aimed to confirm that darbepoetin alfa at a reduced dosing schedule can safely maintain a target hemoglobin level in CRF patients undergoing peritoneal dialysis. Forty-five PD patients receiving r-HuEPO were randomized in a 1:1 ratio to continue r-HuEPO or to change to darbepoetin alfa (open-label). Patients were maintained within a target range of haemoglobin for 5.5 months by adjusting the dose and then the frequency of darbepoetin alfa and r-HuEPO over the initial 4 months. The evaluation period was the final 1.5 months. A total of 37 patients completed the study. During the evaluation period, the hemoglobin of the darbepoetin alfa group was higher than that in the baseline period (10.46 +/- 0.22 g/dL vs. 9.98 +/- 0.18 g/dL, p < 0.05). Hemoglobin remained similar in the r-HuEPO group. The average dose in the darbepoetin alfa group was 93.0 microg/month, while the average dose in the r-HuEPO group was 18,339.9 units/month. The dosing frequency was less in the darbepoetin alfa group (3.9 times/month vs. 9.2 times/month). We divided the darbepoetin alfa group into low-dose (< 70 microg/month) and high-dose (> or = 70 microg/month) subgroups. The body weight in the high-dose group was higher than that in the low-dose group (66 +/- 11 kg vs. 52 +/- 4.4 kg, p < 0.01). Both darbepoetin alfa and r-HuEPO safely maintain hemoglobin levels within the target range in peritoneal dialysis patients.

A retrospective study of clinical use of recombinant human erythropoietin for treatment of anemia in dogs with renal failure in Bangkok, Thailand

The administration of recombinant human erythropoietin (r-HuEPO) for treatment of anemia in dogs with renal failure is practical in most of veterinary hospitals, but there is a variation in clinical use among them. However, the determination of r-HuEPO in dogs has never been addressed in Thailand. Therefore, the objective of the present study was to evaluate the clinical efficacy of r-HuEPO to recover the hematology in dogs that had developed chronic renal failure-induced anemia at the Chulalongkorn Small Animal Teaching Hospital, Thailand. The medical records of the anemic dogs admitted to the hospital were reviewed only in case of treatment with r-HuEPO during the period from January to November 2006. The hematologic and serum biochemical data pre and post-treatment with r-HuEPO were assessed. The results were found that means of packed cell volume (PCV), red blood cell count, and hemoglobin concentration were significantly different from the values at week 0 after only 1 week of r-HuEPO treatment until week 8 of treatment. Erythrocyte indices indicated normocytic and normochromic. Other parameters were insignificant during treatment. In conclusion, treatment with r-HuEPO stimulated erythrocyte production in dogs with naturally developing anemia of chronic renal failure during 8-week treatment period. PCV reached the target range within 6 weeks of treatment. Exogenous r-HuEPO had no effect on leukocyte, platelet counts, and serum biochemistry in these uremic dogs.

Vanadate-Induced Suicidal Erythrocyte Death

Vanadium, a trace element, as vanadate (VO₄^3–) is known to interfere with a wide variety of enzymes including Ca²⁺ ATPase and Na⁺/K⁺ ATPase. VO₄^3– is excreted mainly via the kidney. In renal insufficiency, the impaired VO₄^3– excretion leads to VO₄^3– accumulation in blood.The present study explored the effect of VO₄^3– on eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptotic cells are phagocytosed and thus rapidly cleared from circulating blood. Stimulators of eryptosis include an increase of the cytosolic Ca²⁺ concentration. Erythrocyte Ca²⁺ activity was estimated from Fluo-3 fluorescence, phosphatidylserine exposure from annexin V-binding, and erythrocyte volume from forward scatter in FACS analysis. Exposure of erythrocytes to VO₄^3– increased cytosolic Ca²⁺ concentration, enhanced the percentage of annexin V-binding erythrocytes, decreased erythrocyte forward scatter, and lowered the intracellular ATP concentration. In conclusion, VO₄^3– induces eryptosis at least partially through increase of cytosolic Ca²⁺ concentration, an effect presumably contributing to the development of anemia in chronic renal failure.

Oxidative stress and δ-ALA-D activity in chronic renal failure patients

In this paper, we studied the influence of uremia and hemodialysis on oxidative parameters and δ-aminolevulinic acid dehydratase (δ-ALA-D) activity in control subjects, patients with chronic renal failure (CRF) on hemodialysis treatment (HD) and in patients not undergoing hemodialysis (ND). An increased lipid peroxidation was observed in the serum of HD and ND patients, as measured by the MDA serum levels. However, the level of MDA from erythrocytes was only elevated in HD patients. Blood catalase activity was increased in HD and ND groups. This study also showed a decreased activity of blood δ-aminolevulinic acid dehydratase (δ-ALA-D) in both groups of patients. This study demonstrated a positive correlation between ALA-D activity and hemoglobin, suggesting that inhibition of this enzyme might enhance anemia in CRF. A negative correlation was found between the alteration in δ-ALA-D activity and oxidative stress, which may indicate that the inhibition of ALA-D can be used as an index of oxidative stress.

Erythropoietin in post-resuscitation neurological recovery: is there light at the end of the tunnel?

Studies show that erythropoietin, besides its critical role in hematopoiesis, provides neuroprotection in hypoxic-ischemic cerebral injury. Antiapoptotic, anti-inflammatory, angiogenetic, and neurotrophic properties of erythropoietin could increase indications, currently restricted to anemia in chronic renal failure and cancer, to hypoxic-ischemic cerebral insult.&nbsp;In the adult and neonatal animal model of hypoxic-ischemic cerebral injury, erythropoietin significantly reduces infarct size with attenuation of brain damage, and preservation of&nbsp;cortical integrity. The first human study on the impact of erythropoi-etin in stroke victims showed that erythropoietin is safe and well tolerated at high doses, and associated with improved neurological outcome. Even with intravenous application, concentrations of erythropoietin in cerebrospinal fluid of these patients were many-fold higher than in non-treated patients.&nbsp;In successfully resuscitated cardiac arrest victims overall neurological recovery remains poor despite improved cardiopul-monary resuscitation strategies. Post-resuscitation care needs further advances in order to improve final outcome. Through promotion of neuroangiogenesis, inhibition of hypoxia-induced apoptosis in neurons, and thus support of the survival of neurons in the ischemic brain, erythropoietin could be used to improve functional recovery of these patients. Nevertheless, optimal molecular forms of EPO, therapeutic doses, and treatment time window have to be determined in order to lower the incidence of adverse effects and still preserve neuroprotective properties.&nbsp;