Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats.

AIM: We aimed to investigate the possible cardioprotective effects of paricalcitol (PR), its vitamin D receptor agonist, and vitamin D3 (VIT-D3) on an experimental model of doxorubicin (DX) cardiotoxicity by 99mTc-PYP scintigraphy, electrocardiographic (ECG) and biochemical methods. METHOD: Forty-two male Wistar/Albino rats (250‒300 g; aged 10‒12 weeks) were randomly separated into six groups, namely into control (CN), doxorubicin (DX), paricalcitol (PR), vitamin D3 (VIT-D3), paricalcitol + doxorubicin (PR+DX), and vitamin D3 + doxorubicin (VIT-D3+DX) groups. Cardiotoxicity was induced by three doses of DX (18 mg/kg, i.p.) at 24-hour intervals on days 18, 19 and 20. PR (0.5 ug/ kg, i.p) and VIT-D3 (5,000 IU/kg, i.p) were injected for 20 days before and after the application of DX (18 mg/kg, i.p.). On day 21 of the experiment, biochemical parameters [tumor necrosis factor TNF-alpha (TNF-α); interleukin-6 (IL-6), nitric oxide (NO), and cardiac troponin T (cTnT)], as well as ECG and scintigraphic (99mTc-PYP) features were assessed. RESULTS: Compared to CN, DX significantly raised TNF-α, IL-6, and NO in heart tissue, cTnT in serum, 99mTc-PYP uptake in the myocardium, and ECG parameters, specifically QRS complex duration, QT interval duration, and ST-segment amplitude, while also reducing heart rate (p<0.001). Pretreatment with PR and VIT-D3 mitigated these abnormalities produced by DX in the heart (p<0.001). CONCLUSION: Results show that vitamin D receptor agonist paricalcitol and vitamin D protect against DX-induced cardiotoxicity through anti-inflammatory and antioxidant effects (Fig. 4, Ref. 59). Text in PDF www.elis.sk Keywords: paricalcitol, doxorubicin, vitamin D, ECG, 99mTc-PYP scintigraphy, cardiotoxicity, inflammation.

RDDSVM: accurate prediction of A-to-I RNA editing sites from sequence using support vector machines.

Adenosine to inosine (A-to-I) editing in RNA is involved in various biological processes like gene expression, alternative splicing, and mRNA degradation associated with carcinogenesis and various human diseases. Therefore, accurate identification of RNA editing sites in transcriptome is valuable for research and medicine. RNA-seq is very useful for the detection of RNA editing events in condition-specific cells. However, computational analysis methods of RNA-seq data have considerable false-positive risks due to mapping errors. In this study, we developed a simple machine learning method using support vector machines to train sequence and structure information derived from flanking sequences of experimentally verified A-to-I editing sites to predict new A-to-I editing sites in RNA. The highest performance results were obtained by the model that utilizes the composition of the triplet sequence elements in the flanking regions of the in A-to-I editing sites. Using this model, the SVM classifier also showed high performance on experimentally verified data providing a sensitivity of 92.8%, specificity of 77.1%, and accuracy of 90.2%. To compare the predictive capacity of our method with other classifiers that use sequence information, we have used validated human A-to-I RNA editing sites by Sanger sequencing. Out of 58 validated editing sites, our method recognized 53 of them correctly with an accuracy of 91.4% outperforming other classifiers. As to our knowledge, this is the first case of utilization of the composition of the triplet sequence elements neighboring A-to-I editing sites for the prediction of new A-to-I editing sites in RNA. The methodology is very easy to perform and computationally low demanding making it a convenient and valuable choice for facilities with low sources. To facilitate the usage of the method publicly, we developed an open-source program called RDDSVM to perform prediction on candidate A-to-I RNA editing sites using support vector machines.

Effect of power outages on the use of maternal health services: evidence from Maharashtra, India.

INTRODUCTION: Electricity outages are common in low/middle-income countries and have been shown to adversely affect the operation of health facilities; however, little is known about the effect of outages on the utilisation of health services. METHODS: Using data from the 2015-2016 India Demographic Health Survey, combined with information on electricity outages as reported by the state electricity provider, we explore the associations between outage duration and frequency and delivery in an institution, skilled birth attendance, and caesarean section delivery in Maharashtra State, India. We employ multivariable logistic regression, adjusting for individual and household-level covariates as well as month and district-level fixed effects. RESULTS: Power outage frequency was associated with a significantly lower odds of delivering in an institution (OR 0.98; 95% CI 0.96 to 0.99), and the average number of 8.5 electricity interruptions per month was found to yield a 2.08% lower likelihood of delivering in a facility, which translates to an almost 18% increase in home births. Both power outage frequency and duration were associated with a significantly lower odds of skilled birth attendance (OR 0.97; 95% CI 0.95 to 0.99, and OR 0.99; 95% CI 0.992 to 0.999, respectively), while neither power outage frequency nor duration was a significant predictor of caesarean section delivery. CONCLUSION: Power outage frequency and duration are important determinants of maternal health service usage in Maharashtra State, India. Improving electricity services may lead to improved maternal and newborn health outcomes.

Effect of phosphodiesterase-5 inhibition on joint and muscle damage in rats with adjuvant arthritis

Background/aim: This study was designed to examine the effect of tadalafil, a phosphodiesterase (PDE)5 inhibitor, on the severity of joint and muscle damage in rats with adjuvant-induced arthritis (AA). Materials and methods: AA was induced by intradermal inoculation into right hind paw of male Sprague Dawley rats (300-450g) with complete Freund's adjuvant (CFA; 0.1 mL). AA rats were treated with either tadalafil (10 mg/kg; per oral) alone or along with the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 mg/kg; intraperitoneally). After decapitation on day 16, trunk blood was collected for total oxidant status (TOS) and total antioxidant capacity (TAC) assays. The left metatarsophalangeal joint and gastrocnemius muscle were excised for microscopic examination. Muscle samples were also evaluated in terms of malondialdehyde (MDA), glutathione, and chemiluminescence (CL) levels. Results: In tadalafil-treated AA rats, metatarsophalangeal joints revealed regular morphology of the cartilage with slight destruction and less inflammatory cell infiltration and vascularization in comparison to the controls (microscopic score: 1.17 ± 0.31 vs. 4.17 ± 0.79; P < 0.01). AA rats presented increased gastrocnemius muscle MDA, glutathione, and CL levels compared to the controls (P < 0.01, for MDA; P < 0.05, for glutathione; P < 0.05 for CL). Tadalafil attenuated the increase in CL levels (P < 0.01, for luminol and P < 0.001, for lucigenin). Serum TOS showed significant reductions by tadalafil. Conclusion: The long-acting PDE5 inhibitor tadalafil provides partial protection in a rat model of CFA-induced arthritis possibly via suppression of oxidant generation.

Predictive Value of Mean Platelet Volume in Variceal Bleeding due to Cirrhotic Portal Hypertension.

AIM: To investigate whether mean platelet volume (MPV) is a predictor of variceal bleeding in patients with cirrhotic portal hypertension. MATERIALS AND METHODS: This prospective cohort was performed in the internal medicine department of our tertiary care center. Cirrhotic patients were allocated into two groups: Group I consisted of 31 cases without a history of variceal bleeding, whereas group II was made up of 31 patients with a history of variceal bleeding. Data derived from medical history, physical examination, ultrasonography, gastrointestinal system endoscopy, complete blood count, hepatic, and renal function tests were recorded and compared between two groups. On physical examination, encephalopathy and ascites were evaluated and graded with respect to Child-Pugh-Turcotte classification. RESULTS: There was no significant difference between the two groups in terms of age, duration of the disease, and gender of the patient. The only remarkable difference was that hemoglobin (p = 0.02) and hematocrit (p = 0.02) values were lower in group II. Neither the etiology of bleeding was different between groups nor did MPV seem to have a noteworthy impact on bleeding. Interestingly, risk of variceal bleeding increased in parallel to the higher grade of varices. CONCLUSION: Our results imply that there is a correlation between the grade of varices and esophageal vari-ceal bleeding in cirrhotic patients. However, association between MPV and variceal bleeding could not be demonstrated. Utilization of noninvasive tests as predictors in these patients necessitates further controlled trials on larger series.How to cite this article: Erdogan MA, Benli AR, Acmali SB, Koroglu M, Atayan Y, Danalioglu A, Kayhan B. Predictive Value of Mean Platelet Volume in Variceal Bleeding due to Cirrhotic Portal Hypertension. Euroasian J Hepato-Gastroenterol 2017;7(1):6-10.

Assessing Safety of Pneumatic Tube System (PTS) for Patients with Very Low Hematologic Parameters.

BACKGROUND Preventive interventions save lives during the process of chemotherapy for hematologic malignancies, when a hematology laboratory can ensure accurate results. The use of a pneumatic tube system (PTS) is associated with measurement errors and unnecessary transfusions. The aim of this study was to evaluate pre-analytical errors associated with transportation method (PTS versus hand-delivered) and to investigate whether there are unnecessary transfusion events in pancytopenia leukemia patients with very low hematological parameters. MATERIAL AND METHODS A total of 140 paired blood collections were performed for hemogram and biochemistry assays. Paired EDTA and serum gel blood samples were collected from 58 cases with acute leukemia on different days. For each pair, one sample was hand-delivered by a courier (Group 1) while the other sample was transported through a PTS (Group 2). RESULTS The hand-delivered method showed that some platelet transfusions were unnecessary for different thrombocyte cut-off values. Calculated unnecessary platelet (PLT) transfusion ratios when using PTS (PLT <30×10³/µL, 16.3%; PLT <25×10³/µL, 16.4%; PLT <20×10³/µL, 80.3%; PLT <15×10³/µL, 48.6%; and PLT <10×10³/µL, 150.0%) were found to be statistically significant (p=0.002, p=0.046, p<0.000, p=0.028, and p<0.000, respectively). In contrast, for RBC transfusion ratios, although the ratios were high in Group 2, we found no significant difference between the two groups; (HGB <8.0 g/dL, 23.3%; HGB <9.0 g/dL, 25.0%, HGB<10.0 g/dL, 19.3%) and (p=0.002, p=0.085, p<0.160, and p=0.235, respectively). CONCLUSIONS Although our results cannot be universally applied, physicians should be careful, skeptical, and suspicious of transfusion decisions in hematology clinics and consider potential analytical and pre-analytical errors in cases of severe cytopenia when using PTS.

DHAP plus filgrastim as an effective peripheral stem cell mobilization regimen for autologous stem-cell transplantation in patients with relapsed/refractory lymphoma: A single center experience.

This study aimed to evaluate the efficiency of DHAP regimen plus filgrastim for mobilization of stem cells in patients with recurrent and/or refractory lymphoma. Thirty-four patients who took DHAP as salvage therapy prior to autologous stem cell transplantation were included. After chemotherapies, 2 cycles of DHAP plus filgrastim were administered to the patients. Stem cells from 32 patients (94%) were collected on median 11th day (8-12), and the median collected CD34(+) cell dose was 9.7 × 10(6)/kg (range 3.8-41.6). DHAP plus filgrastim was found to be an effective chemotherapy regimen in mobilizing CD34(+) stem cells into the peripheral.

Moxifloxacin related thrombocytopeniae: A case report.

Drug-induced thrombocytopenia can be caused by various medications, most frequently, antibiotics. There have been reports of thrombocytopenia cases due to the usage of quinolone antibiotics, although moxifloxacin-related thrombocytopenia has been reported very rarely. The case is here presented of a 60-year old male with chronic obstructive pulmonary disease who presented with complaints of progressively worsening dyspnea. After hospitalization, progressive thrombocytopenia was detected which had started on the 3rd day of moxifloxacin treatment. Other causes of thrombocytopenia were excluded and the thrombocyte count returned to normal after discontinuation of moxifloxacin.

Leukapheresis treatment in elderly acute leukemia patients with hyperleukocytosis: A single center experience.

AIM: Leukapheresis is an invasive treatment modality used for hyperleukocytosis. Various drugs and fluids are used during the leukapheresis. Aging itself and associated factors such as increased comorbidity, decreased tolerance to drugs, increased drug toxicity give rise to the application of other treatment modalities in elderly patients. Treatment of acute leukemia in the elderly differs from young patients. Consequently, we assumed that outcome, effectiveness, and side effects of leukapheresis treatment used for acute leukemia patients with hyperleukocytosis may be different in elderly compared to younger patients. METHODS: We retrospectively evaluated a total of 39 patients. Eighteen patients were 65 years and older. Indications for leukapheresis were determined as symptoms of leukostasis and prophylaxis. Acid citrate dextrose-A, calcium gluconate, and plasma were used during the leukapheresis. Age, sex, diagnosis, count, and indications of leukapheresis procedures, leukocyte count, and lactate dehydrogenase level were analyzed at the onset of and after leukapheresis; side effects, causes of death, early and total mortality rates were also analyzed. We compared the two groups with regard to effectiveness, clinical outcomes, and side effects. RESULTS: There were no statistically significant differences between the two groups with respect to sex, diagnosis, initial leukocyte count, lactate dehydrogenase level, number of leukapheresis procedures, rates of side effects, or early and total mortality (P > 0.05). Leukapheresis treatment was effective in both groups (P < 0.05) and no significant difference was found in its effectiveness between two groups (P > 0.05). CONCLUSION: Leukapheresis is an effective and safe treatment modality in elderly acute leukemia patients with hyperleukocytosis.

Can BuCyE conditioning regimen be an alternative treatment to BEAM at autologous transplantation in malignant lymphoma patients?: a single center experience.

High-dose chemotherapy (HDC) applied together with autologous stem cell transplantation (ASCT) is a commonly used treatment modality in patients with malignant lymphoma. At present, there is a limited number of studies which compare toxicity and efficacy of various high-dose regimens applied in the treatment of malignant lymphoma. For this reason, the aim of this study was to investigate the efficacy and toxicity of BuCyE (busulfan, cyclophosphamide and etoposide) and BEAM (carmustine, etoposide, cytarabine and melphalan) preparative regimens in the patients with malignant lymphoma scheduled for autologous stem cell transplantation. Between November, 2010 and April, 2015, 42 patients with relapsed or refractory malignant lymphoma who underwent autologous stem cell transplantation following BEAM (n=11) and BuCyE (n=31) preparative regimens were analyzed at Bone Marrow Transplantation Unit of TurgutOzal Medicine Center in Turkey. The groups were compared in terms of patient characteristics, hematopoietic engraftment time, toxicity profiles and survival. No significant differences were detected between the groups with regard to age, gender distribution, international prognostic index, ASCT indications, disease status at the time of ASCT and type of lymphoma (P>0.05). Median number of infused CD34+ cells/kg, neutrophil and platelet engraftment statuses of BuCyE and BEAM groups were found to be similar (P>0.05). More patients in BuCyE group developed mucositis and nausea, but this difference was not statistically significant (P>0.05). A similar statistically insignificant difference was seen in that infectious complications occurred more commonly in BEAM group (P>0.05). Overall survival and event-free survival rates were not significantly different between the groups (P>0.05). BuCyE is a conditioning regimen which can be effectively used as an alternative to BEAM in the patients with malignant lymphoma undergoing ASCT. Moreover, toxicity rates of both regimens are similar. In order to comprehend the effect of each HDC regimen, further evidence-based data obtained from the studies involving larger sample sizes are required.

Leukapheresis in acute myeloid leukemia patients with hyperleukocytosis: A single center experience.

Hyperleukocytosis is defined as WBC count above 100,000/mm(3) in peripheral blood. Increased WBC count leads to leukocyte aggregation, increased blood viscosity, and consequently results in stasis in small blood vessels. Ultimate neurological, pulmonary, gastrointestinal complications, coagulopathy, and tumor lysis syndrome cause increase in morbidity and mortality. Leukapheresis is a treatment modality used for hyperleukocytosis. In patients presenting with hyperleukocytosis the indications for leukapheresis were accepted as having symptoms of leukostasis and prophylactic. Indications for leukapheresis in prophylactic group evaluated according to WBC count. We report a single center experience about leukapheresis in managing 31 AML patients with hyperleukocytosis. In addition to demographic characteristics, disease-related clinical and laboratory findings of the patients were recorded. Survival rates were also calculated. Ten patients were female. The most common of AML subtype was AML-M2. The median number of leukapheresis per patient was 2 and totally 60 leukapheresis cycles were performed in all patients. There was a significant decrease in WBC count and LDH level after leukapheresis as compared with the baseline values (p < 0.05). Early and total mortality were 16.1% and 58.0%, respectively. Alive and died patients were evaluated according to baseline WBC, LDH; increased WBC count and LDH level were found in died patients (p < 0.05). According to leukapheresis indications, patients were divided into two groups: 14 patients in symptomatic leukostasis, 17 patients in prophylaxis. No statistically significant differences were noted between both groups in leukapheresis effectiveness, mean survival time, early and total mortality rate (p > 0.05). None of our patients suffered serious side effects and tumor lysis syndrome during or after apheresis. Leukapheresis is an effective and safe approach to reduce WBC counts in patients with AML with hyperleukocytosis. Further evidence-based data obtained from larger sample sizes are required to better understand the impact of prophylaxis leukapheresis on early and total mortality of AML patients with hyperleukocytosis.

A life-saving therapy in Class I HELLP syndrome: Therapeutic plasma exchange.

HELLP syndrome, which can affect multiple organ systems and cause maternal and fetal mortality, is a serious complication of pregnancy characterized by microangiopathic hemolytic anemia, elevation of liver enzymes, and thrombocytopenia. Delivering the infant usually suffices for the treatment of this syndrome. In cases with Class I HELLP syndrome, however, the clinical picture may rapidly deteriorate despite delivery. In this paper we presented the outcomes with the use of therapeutic plasma exchange in cases with class I HELLP syndrome. This study included 21 patients diagnosed with the Class I HELLP syndrome at Inonu University Faculty of Medicine, Department of Hematology between 2011 and 2014. A central venous catheter was placed and plasma exchange therapy was begun in patients unresponsive to delivery, steroid, and supportive therapy (blood and blood products, antihypertensive therapy, intravenous fluid administration, and antibiotics) within 24 hours after the diagnosis of Class I HELLP syndrome according to the Mississippi Criteria. All patients underwent therapeutic plasma exchange for three sessions each with a 1:1 volume. Hemogram and biochemical parameters of the patients were evaluated before and after the procedure. According to results, there was a statistically significant decrease in total bilirubin, LDH, AST, and ALT levels whereas a significant increase in platelet count was observed. Hemoglobin levels were increased, although this increase was not statistically significant. HELLP syndrome is primarily treated with the delivery of infant; however, some cases may show disease progression despite completion of delivery. As a potential cause of both maternal and fetal mortality, HELLP syndrome condition should be aggressively treated. Therapeutic plasma exchange is one of the available treatment options. Our study has found that postpartum use of plasma exchange therapy within 24 hours is an efficient and lifesaving treatment choice in Class I HELLP syndrome.

Effect of maternal age on pregnancy outcome and cesarean delivery rate.

BACKGROUND: The aims of this retrospective study were to evaluate the maternal and prenatal outcomes between 35 years and older pregnancies and younger pregnancies, and the effects of the age of pregnancy, mother and newborn. METHODS: Pregnant women who gave birth in Vakif Gureba Training and Research Hospital, Clinic of Obstetrics and Gynecology in 2006 were retrospectively screened. Pregnant women aged 35 years and over were included in this study and the pregnant women between age range of 30 - 34 years were included in the control group. RESULTS: Pregnancy rate was found as 7.1% in 35 years and older women in all the deliveries, cesarean delivery rate was found as 46.1% in this group at 1 year period. However, cesarean delivery rate was 40.9% in the control group. Cesarean delivery rate was found as 31.6% in all the deliveries. The most common cause of cesarean section indication was fetal distress in advanced maternal age (AMA) (11.7%), whereas previous cesarean section was found as the most common cause in the control group (15.1%). CONCLUSION: No significant difference was found between AMA group and normal pregnancies in terms of preterm labor, caesarian section, morbidity, mortality and chronic diseases such as hypertension and diabetes mellitus.

Hermansky-pudlak syndrome: a case report.

Objective. The aim of this paper is to report the case of a patient diagnosed with Hermansky-Pudlak syndrome, as a result of bleeding diathesis. Clinical Presentation and Intervention. A 23-year-old male presented with recurrent epistaxis and, upon physical examination, was found to be remarkable for albinism and suborbital ecchymosis. The absence of dense bodies in the platelets was demonstrated using electron microscopy. This patient was (slowly) administered one unit of a platelet suspension, and his bleeding decreased considerably. Conclusion. This case shows that Hermansky-Pudlak syndrome should be considered in the differential diagnosis of a patient presenting with bleeding diathesis, when the clinical presentation also includes oculocutaneous albinism and visual problems.

An unexpected complication of bone marrow aspiration and trephine biopsy: arteriovenous fistula.

OBJECTIVE: To report a case of arteriovenous fistula (AVF) following bone marrow aspiration and trephine biopsy. CLINICAL PRESENTATION AND INTERVENTION: A 76-year-old man was diagnosed with acute myeloblastic leukemia. Pain and hematoma were detected in his left leg and hip 4 days after bone marrow aspiration and trephine biopsy. A pelvic arteriography was performed, and a diagnosis of AVF was made. CONCLUSION: This case shows that clinicians should be aware of AVF, especially in cases with refractory bleeding after bone marrow aspiration and trephine biopsy despite normal blood coagulation parameters.

Primarily unknown origin adenocarcinoma metastasis in bone marrow presenting with thrombotic thrombocytopenic purpura: a case report.

We report a case of thrombotic thrombocytopenic purpura refractory to plasma exchange treatment. In bone marrow examination non hematopoetic cell groups have seen. But the primary tumor could neither be located endoscopically nor in imaging examinations. Upon the bone marrow biopsy confirm the adenocarcinoma metastasis an objective improvement have achived in the blood picture after polychemotherapy.

Therapeutic plasma-exchange in hematologic disease: results from a single center in Eastern Anatolia.

Therapeutic plasma-exchange (TPE) is used as primary and adjunctive therapy in treatment of several hematologic diseases. We retrospectively evaluated the results of TPE in hematologic diseases during 2008-2012. A total of 301 TPE procedures were performed in 44 patients (19 male and 25 female, with mean age of 50.6±15years). Fifteen of 44 patients had thrombotic thrombocytopenic purpura (TTP), 14 patients had HELLP syndrome (Hemolysis Elevated Liver enzymes, Low Platelet count), 10 patients had multiple myeloma-hyperviscosity and the rest five patients had snake bite. Fresh frozen plasma (FFP) was used as replacement fluid. Complete response (CR) was achieved on 13 patients (87%) in primarily TTP. CR was achieved in all other three diseases. Total complications were detected in 8.1% of the TPE procedures. Adverse events (AEs), were seen in 5.4% of all procedures. None of the patients died from any complication. AE occurred in 4% (Grade-I), 1% (Grade-II), and 0.3% (Grade-III) of the procedures. The most common AE were nausea/vomiting, hypotension, pruritus and abdominal pain. TPE is effectively and safely carried out in our center in hematologic diseases.

Pulmonary embolism as the initial presentation of testicular carcinoma.

Objective. The risk of pulmonary embolism is well recognized as showing an increase in oncological patients. We report a case presenting with pulmonary embolism initially, which was then diagnosed with testicular cancer. Clinical Presentation and Intervention. A 25-year-old man was admitted to the emergency department with a complaint of dyspnoea. Thoracic tomography, lung ventilation/perfusion scintigraphy, and an increased D-dimer level revealed pulmonary embolism. For the aetiology of pulmonary embolism, a left orchiectomy was performed and the patient was diagnosed with a germinal cell tumour of the testicle. Conclusion. In this paper, we present a patient for whom pulmonary embolism was the initial presentation, and a germinal cell tumour was diagnosed later during the search for the aetiology.

A Rare Disease in Adult: Langerhans Cell Histiocytosis.

Langerhans cell histiocytosis is a rare histiocytic disorder and has been diagnosed in all age groups, but is most common in children. This disease is very rare in adults. We presented a patient who was 62 years old man diagnosed langerhans cell histiocytosis.

Erythropoiesis stimulatory agent- resistant anemia in dialysis patients: review of causes and management.

Despite new therapeutic options and treatment strategies, anemia still remains one of the major complications of chronic kidney disease (CKD), especially in patients undergoing chronic hemodialysis for end-stage renal disease. Successful management of anemia is a central part of patient care that may improve clinical outcomes. Although the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) working group reformulated its recommendations by stating that the hemoglobin target in patients receiving erythropoiesis stimulatory agents (ESA) should generally be 11-12 g/dl, this target value can not be achieved in many of them, despite treatment with high doses of ESA. The aim of the present review is to provide an update of the recent literature on causes and possible management of ESA-resistant anemia in CKD patients.