The effectiveness of ruxolitinib and cyclophosphamide combination on T helper 17 and regulatory T cells in rat experimental membranous glomerulonephritis.

The progression and pathogenesis of membranous glomerulonephritis (MGN) are inextricably linked to chronic inflammation. Despite improving clinical remission rates due to the application of cyclophosphamide (CYC), treatment of MGN still requires further exploration. Ruxolitinib (Ruxo) negatively affects the signaling pathways participating in the production of pro-inflammatory cytokines. Hence, we investigated whether the combination of CYC and Ruxo can modulate inflammation through influencing T helper 17 (Th17) lineages and regulatory T cells (Tregs). Passive Heymann nephritis (PHN), an experimental model of MGN, was induced in a population of rats. Then, the animals were divided into five groups: PHN, CYC-receiving, Ruxo-receiving, CYC-Ruxo-receiving PHN rats, and healthy controls. After 28 days of treatment, biochemistry analysis was performed and splenocytes were isolated for flowcytometry investigation of Th17 cells and Tregs. The correlative transcription factors of the cells, alongside their downstream cytokine gene expressions, were also assessed using real-time PCR. Furthermore, serum cytokine signatures for the lymphocytes were determined through ELISA. The combination of CYC and Ruxo significantly reduced the serum values of urea in rats versus the PHN group (24.62 ± 7.970 vs. 40.60 ± 10.81 mg/dL). In contrast to Treg's activities, the functionality of Th17 cells noticeably increased not only in PHN rats but also in CYC or Ruxo-receiving PHN animals when compared with the control (10.60 ± 2.236, 8.800 ± 1.465, 8.680 ± 1.314 vs. 4.420 ± 1.551 %). However, in comparison to the PHN group, the incidence of Th17 cells notably fell in rats receiving CYC and Ruxo (10.60 ± 2.236 vs. 6.000 ± 1.373 %) in favor of the Treg's percentage (5.020 ± 1.761 vs. 8.980 ± 1.178 %), which was verified by the gene expressions and cytokine productions correlative to these lymphocytes. The combination of CYC and Ruxo was able to decline Th17 cells in favor of Tregs improvement in PHN rats, suggesting an innovative combination therapy in MGN treatment approaches.

Glucocorticoid Receptor Polymorphisms and Avascular Osteonecrosis After Kidney Transplantation.

INTRODUCTION: Glucocorticoids (GCs) are commonly prescribed as immunosuppressive agents after kidney transplantation and their most common non-traumatic adverse effect is Avascular Necrosis (AVN) of the femoral head. In this regard, this study aimed to evaluate the glucocorticoid receptor (GR) polymorphisms among kidney transplant recipients and their potential role as a risk factor for the incidence of AVN. METHODS: In this study, 99 renal transplant recipients were evaluated for the correlations of GR polymorphisms including N363S (rs6195), BclI (rs41423247), ER22/23EK (rs6189/rs6190), and A3669G (rs6198) with AVN after renal transplantation. RESULTS: Results showed that none of the renal-transplanted patients neither with GC hypersensitive polymorphisms (N363S and BclI) nor with GC-resistant polymorphisms (A3669G and ER22/23EK) developed AVN (P > .05). In addition, the medications of the renal recipients with AVN were significantly different from the nonAVN patients (P < .001). CONCLUSION: The study results indicate that the GR polymorphisms have no critical roles in the susceptibility to AVN after renal transplantation. However, further studies to confirm the results are recommended.  DOI: 10.52547/ijkd.7221.

Evaluation of the immune checkpoint factors in idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B-cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.

Evaluation of T helper17 as skeletal homeostasis factor in peripheral blood mononuclear cells and T helper cells of end-stage renal disease cases with impaired parathyroid hormone.

BACKGROUND: Chronic renal failure is mainly connected with high and low parathyroid hormone (PTH) levels and immunological impairments. The present study aimed to evaluate T helper 17 (Th17) cells as a crucial modulator of the immune system and skeletal homeostasis in hemodialysis patients with impaired intact PTH (iPTH). METHODS: In this research, blood samples were taken from ESRD patients with high (> 300 pg/mL), normal (150-300 pg/mL), and low (< 150 pg/mL) serum intact parathyroid hormone (iPTH( levels (n = 30 in each group). The frequency of Th17 (CD4+ IL17+) cells was evaluated by flow cytometry in each group. The expression levels of Th17 cell-related master transcription factors, cytokines in peripheral blood mononuclear cells (PBMC), and Th cells, and the level of the mentioned cytokines were determined in the supernatant of PBMCs. RESULTS: The number of Th17 cells remarkably increased in subjects with high iPTH against low and normal iPTH. Also, RORÉ£t and STAT3 levels were significantly higher in high iPTH ESRD patients than in other groups in the expression of mRNA and protein levels. These findings are confirmed by evaluating the IL-17 and IL-23 in the supernatant of cultured PBMCs and isolated Th cells. CONCLUSION: Our findings indicated that increased serum PTH levels in hemodialysis cases may be involved in increasing the differentiation of CD4 + cells to Th17 cells in PBMC.

Potent SARS-CoV2-specific T-cell response in asymptomatic hemodialysis patients with hidden COVID-19 infection history.

BACKGROUND: COVID-19-related immune responses in patients with end-stage renal disease (ESRD) are characterized in detail by the humoral response, but their cellular immunity has not been clarified. Here, we evaluated virus-specific T cells in parallel with serology-related tests. METHODS: In this study, 104 ESRD patients at the hemodialysis ward of Imam Reza hospital at Tabriz (Iran) were enrolled. After blood sampling, SARS-CoV2-specific humoral and cellular immune responses were evaluated by SARS-CoV2-specific IgM/IgG ELISA and peptide/MHCI-Tetramers flow cytometry, respectively. RESULTS: Our results showed that 14 (13.5%) and 45 (43.3%) patients had specific SARS-CoV2 IgM and IgG in their sera, respectively. Immunophenotyping for SARS-CoV2-specific CD8+ T lymphocytes revealed that 68 (65.4%) patients had these types of cells. Among SARS-CoV2-specific CD8+ T lymphocytes positive subjects, 13 and 43 individuals had positive results for specific SARS-CoV2 IgM and IgG existence, respectively. Also, there was a relationship between specific SARS-CoV2 IgM (p = 0.031) and IgG (p < 0.0001) existence and having SARS-CoV2-specific TCD8+ lymphocytes in the studied population. CONCLUSION: Despite not having clinical symptoms, a high rate of SARS-CoV2-specific T-cell response in asymptomatic ESRD patients may reveal a high burden of asymptomatic COVID-19 infection in these patients.

Expression level of immune checkpoint inhibitory factors in preeclampsia.

Preeclampsia (PE) is a severe complication in pregnancy, and its symptoms (proteinuria and hypertension) manifest after 20 weeks of gestation, affecting up to 8 % of pregnancies. The pregnant women's immune system uses different tolerance mechanisms to deal with a semi-allogeneic fetus. The T-cell subsets including CD8+, CD4+, and Treg play a critical role in maintaining pregnancies. The expression of immune checkpoint molecules in T-cells can ensure pregnancy at the feto-maternal interface by controlling immune responses. This research aims to evaluate the expression level of immune checkpoint factors, including PD-1, LAG-3, CTLA-4, and TIM-3 in normal pregnant women and PE patients. Decidual tissue was collected from 50 participants (25 PE and 25 control). For evaluating the genes expression, real-time PCR was employed. The western blot was used to assess the proteins level. The results of real-time PCR indicated significantly decreased expression level of these immune checkpoints in PE patients. In parallel to gene expression results, the protein level of PD-1, LAG-3, CTLA-4, and TIM-3 in the PE group was also reduced. We revealed that the profile of proteins and genes expression of immune checkpoints in the decidua of PE mothers are different from normal pregnancy and these results indicate aberrant expression of immune checkpoints such as PD-1, LAG-3, CTLA-4, and TIM-3 may cause maladaptation immune response which results in PE manifestation.

Potential contribution of the immune system to the emergence of renal diseases.

Several parts are possessed by kidneys in fundamental physiological functions, which include the regulation of blood pressure, production of blood cells, homeostasis of water, salt, and calcium, and the balance of acids and bases. Thus, several pathologies could cause, or be caused by, renal dysfunction. Chronic kidney failure, or chronic kidney disease, is described as the time when kidneys lose their function gradually. Excess fluids and wastes are filtered from the blood and excreted to urine by kidneys. However, in case of advanced stages of chronic kidney failures, deleterious levels of wastes, electrolytes, and fluids could be observed in the body. The activation of immune system, as well as inflammation, are factors with paramount significance in the development of chronic and acute renal failure. Two main branches, including innate and adaptive immunity, compose the immune system. As the first responder, the innate immunity responds nonspecifically to invading pathogens. However, the adaptive immunity provides efficient recognition and response to particular pathogens, and enjoys a memory which is useful in second exposure to a pathogen. Different functions, the mediation of which takes place through cytokines, immune cell subsets, and protein cascades, are performed by these two immune responses. This review is aimed at focusing on data which have linked adaptive immunity, particularly T-cells and inflammatory mechanisms, to the development of renal failure.

Prevalence of SARS-CoV-2 Specific Antibodies in Asymptomatic Hemodialysis Patients.

BACKGROUND: Since the outbreak of the new coronavirus pandemic, the importance of carrying out an infection check to prevent acquisition and transmission among end-stage renal disease patients (ESRD) under maintenance hemodialysis (MHD) has become a major concern in the health care system. Applying serology screening tests could enlighten the view with regards to disease prevalence in dialysis wards. METHODS: We subjected 328 end-stage renal disease patients to maintenance hemodialysis. After dividing patients into suspicious and non-suspicious groups for COVID-19 infection based on their clinical manifestation, they were investigated for SARS-CoV-2 specific IgM and IgG screening against nucleoprotein (NP), spike protein (SP), and receptor-binding domain (RBD), utilizing our recently developed ELISA tests. RESULTS: We found that approximately 10.1% of asymptomatically tested cases were antibody positive. Although IgG positivity showed a higher prevalence than IgM across all three virus antigen subunits, there were no significant differences among mentioned immunoglobulins of the studied groups. The most prevalent antibody was from the IgG subtype against virus nucleoprotein (NP), while the lowest prevalence was attributed to receptor-binding domain (RBD) IgM. CONCLUSION: High seropositive rate among asymptomatic end-stage renal disease patients, as a sample of high-risk population, reflected the importance of considering SARS-CoV-2 specific antibody screening for disease containment.

The Effects of Cholecalciferol Supplementation on FGF23 and α-Klotho in Hemodialysis Patients With Hypovitaminosis D: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Vitamin D-fibroblast growth factor-23 (FGF-23)-klotho forms an axis that takes part at least in cardiovascular complications in patients with chronic kidney disease. This study aimed to assess the effects of cholecalciferol supplementation on FGF23 and α-klotho in patients with hypovitaminosis D requiring hemodialysis. METHODS: In a single-center, parallel-arm, randomized, double-blind, placebo-controlled trial, 86 patients with hypovitaminosis D requiring hemodialysis were enrolled. The patients were randomized into 2 groups (n = 43 each) to receive either 50,000 IU of cholecalciferol or placebo every week for 12 weeks. Accordingly, the serum levels of FGF23 and klotho were measured by ELISA and compared between both groups. RESULTS: Serum 25OH(D) levels increased in participants who received cholecalciferol supplementation compared with participants who received placebo (P = .006). In addition, serum FGF23 decreased and α-klotho levels increased in the supplemented group compared with placebo. However, the before-after differences between cholecalciferol supplement and placebo were significant only for α-klotho (P = .035). These effects were not accompanied by changes in the levels of phosphate, total and ionized calcium, and intact parathyroid hormone. CONCLUSION: Cholecalciferol supplementation of 50,000 IU for 12 weeks increases α-klotho levels in the serum of kidney failure patients undergoing hemodialysis. This may suggest that patients receiving maintenance hemodialysis can benefit from using cholecalciferol supplementation and increase in serum α-klotho levels.

The clinical significance of the glucocorticoid receptors: Genetics and epigenetics.

The impacts of glucocorticoids (GCs) are mainly mediated by a nuclear receptor (GR) existing in almost every tissue. The GR regulates a wide range of physiological functions, including inflammation, cell metabolism, and differentiation playing a major role in cellular responses to GCs and stress. Therefore, the dysregulation or disruption of GR can cause deficiencies in the adaptation to stress and the preservation of homeostasis. The number of GR polymorphisms associated with different diseases has been mounting per year. Tackling these clinical complications obliges a comprehensive understanding of the molecular network action of GCs at the level of the GR structure and its signaling pathways. Beyond genetic variation in the GR gene, epigenetic changes can enhance our understanding of causal factors involved in the development of diseases and identifying biomarkers. In this review, we highlight the relationships of GC receptor gene polymorphisms and epigenetics with different diseases.

The lethal internal face of the coronaviruses: Kidney tropism of the SARS, MERS, and COVID19 viruses.

The kidney is one of the main targets attacked by viruses in patients with a coronavirus infection. Until now, SARS-CoV-2 has been identified as the seventh member of the coronavirus family capable of infecting humans. In the past two decades, humankind has experienced outbreaks triggered by two other extremely infective members of the coronavirus family; the MERS-CoV and the SARS-CoV. According to several investigations, SARS-CoV causes proteinuria and renal impairment or failure. The SARS-CoV was identified in the distal convoluted tubules of the kidney of infected patients. Also, renal dysfunction was observed in numerous cases of MERS-CoV infection. And recently, during the 2019-nCoV pandemic, it was found that the novel coronavirus not only induces acute respiratory distress syndrome (ARDS) but also can induce damages in various organs including the liver, heart, and kidney. The kidney tissue and its cells are targeted massively by the coronaviruses due to the abundant presence of ACE2 and Dpp4 receptors on kidney cells. These receptors are characterized as the main route of coronavirus entry to the victim cells. Renal failure due to massive viral invasion can lead to undesirable complications and enhanced mortality rate, thus more attention should be paid to the pathology of coronaviruses in the kidney. Here, we have provided the most recent knowledge on the coronaviruses (SARS, MERS, and COVID19) pathology and the mechanisms of their impact on the kidney tissue and functions.

Roles of microRNAs in renal disorders related to primary podocyte dysfunction.

Through the regulation of gene expression, microRNAs (miRNAs) are capable of modulating vital biological processes, such as proliferation, differentiation, and apoptosis. Several mechanisms control the function of miRNAs, including translational inhibition and targeted miRNA degradation. Through utilizing high-throughput screening methods, such as small RNA sequencing and microarray, alterations in miRNA expression of kidneys have recently been observed both in rodent models and humans throughout the development of chronic kidney disease (CKD) and acute kidney injury (AKI). The levels of miRNAs in urine supernatant, sediment, and exosomal fraction could predict novel biomarker candidates in different diseases of kidneys, including IgA nephropathy, lupus nephritis, and diabetic nephropathy. The therapeutic potential of administrating anti-miRNAs and miRNAs has also been reported recently. The present study is aimed at reviewing the state-of-the-art research with regards to miRNAs involved in renal disorders related to primary podocyte dysfunction by laying particular emphasis on Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN).

Altered Th17/Treg ratio as a possible mechanism in pathogenesis of idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) as a single organ autoimmune disease is a main cause of nephrotic syndrome in adults which is determined through autoantibodies to podocytes proteins. Th17/regulatory T (Treg) balance has emerged as a prominent factor in the regulation of autoimmunity. In this study, we evaluated the balance of Th17 and Treg cells, expression level of related master transcription factors, cytokines and microRNAs in mononuclear cells of peripheral blood of 30 patients with IMN and 30 healthy individuals before treatment. No significant variation was observed in Th17 cell frequency, retinoic acid receptor-related orphan nuclear receptor γt (RORÉ£t), signal transducer and Activator of transcription 3(STAT3), IL-17, and IL-23, while IL-21, IL-4, and IL-10 had significant increase in mRNA expression and protein level of peripheral blood mononuclear cells in IMN cases. Reduction in the percentage of Treg cells was also accompanied with significantly decreased expression of Forkhead box P3(FOXP3) and Transforming growth factor beta(TGF-ß) in IMN patients compared to the control group. Our study revealed that Th17 cells themselves might not be engaged in the pathogenesis of newly diagnosed patients with IMN; however, decreased T reg cells and increased ratio of Th17/Treg lymphocytes might display a role in the pathogenesis of IMN before treatment.

COVID-19: Our Current Knowledge of Epidemiology, Pathology, Therapeutic Approaches, and Diagnostic Methods.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) firstly emerged in Wuhan, China at the end of 2019. After going through the experimental process, the virus was named the novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in February 2020 which has created a global pandemic. The coronavirus disease 2019 (COVID-19) infection is challenging the people who are especially suffering from chronic health problems such as asthma, diabetes, and heart disease or immune system deteriorating disorders, including cancers, Alzheimer's, etc. Other predisposing/risk factors consist of smoking and age (elderly people are at higher risk). The 2019-nCoV attacks epithelial cells in all organs, particularly epithelial cells in the lungs, resulting in viral pneumonia. The 2019-nCoV starts its invasion with the attachment and entry into the respiratory tract epithelial cells via Angiotensin-Converting Enzyme 2 (ACE2) receptors on the epithelial cells. The critical problem with 2019-nCoV is its ability in human to human asymptomatic transmission which causes the rapid and hidden spread of the virus among the population. Also, there are several reports of highly variable and tightly case-dependent clinical manifestations caused by SARS-CoV2, which made the virus more enigmatic. The clinical symptoms are varied from common manifestations which occurred in flu and cold, such as cough, fever, body-ache, trembling, and runny nose to severe conditions, like the Acute Respiratory Distress Syndrome (ARDS) or even uncommon/unusual symptoms such as anosmia, skin color change, and stroke. In fact, besides serious injuries in the respiratory system, COVID-19 invades and damages various organs, including the kidney, liver, gastrointestinal, and nervous system. Accordingly, to cut the transmission chain of disease and control the infection spread. One of the major solutions seems to be early detection of the carriers, particularly the asymptomatic people, with sensitive and accurate diagnostic techniques. Moreover, developing novel and appropriate therapeutic approaches will contribute to the suitable management of the pandemic. Therefore, there is an urgent necessity to make comprehensive investigations and study reviews about COVID-19, offering the latest findings of novel therapies, drugs, epidemiology, and routes of virus transmission and pathogenesis. In this review, we discuss new therapeutic outcomes and cover and the most significant aspects of COVID-19, including the epidemiology, biological features, organs failure, and diagnostic techniques.

Immune system-mediated cellular and molecular mechanisms in idiopathic membranous nephropathy pathogenesis and possible therapeutic targets.

Idiopathic membranous nephropathy (IMN) has recently attracted much attention due to the development of auto antibodies, anti-phospholipase A2 receptor and anti-thrombospondin type I domain-containing 7A on podocytes, the establishment of immune networks complexes in circulation as well as the development of autoreactive immune cells against kidney, in both innate and adaptive participants. The auto inflammatory responses in IMN leads to the dysfunction of glomerular cells to represent pathological status. T cells, as a crucial factor in the immune network, support B cell-related responses and develop inflammation and cytotoxicity. They have the most determining roles in the autoimmune diseases. Activation of T cells occurs just before their infiltration in kidney. This process is definitely accompanied by costimulatory factors and cytokines, in order to develop and increase the number of these cells. In addition, altered B cell signaling network by the B cell receptor and co receptors such as B cell-activating factor receptor (BAFFR) stimulates the autoimmune-related pathogenesis. Autoantigens exposure and kidney infiltration of naive T cells lead to their local development. Furthermore, losing peripheral immune tolerance towards kidney antigens, will result in IMN. The growing findings about different immune system factors, cells and molecular mechanism have also revealed new pathways of pathogenesis and diagnosis approaches, such as personalized medicine in MN patients. This review aims to discuss the recent findings in adaptive immune cells, and distinguishes between intact and undone researches about pathogenesis and molecular signaling pathways of immune system in MN disease.

Plasma levels of miR-21, miR-150, miR-423 in patients with lupus nephritis.

INTRODUCTION: MicroRNAs (miRNA) are involved in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease, and can be considered as diagnostic and prognostic biomarkers. Lupus nephritis (LN) remains a major challenge of SLE since it damages the kidneys in the course of the disease. METHODS: The aim of this study was to investigate the diagnostic values of circulating miR-21, miR-148a, miR-150, and miR-423 involved in autoimmunity and kidney fibrosis in plasma samples of LN cases (N = 26) and healthy controls (N = 26) using quantitative- PCR (qPCR). The possible associations between the microRNAs and clinical parameters and their diagnostic values were also calculated. RESULTS: The levels of circulating miR-21 (P < .001) and miR-423 (P < .05) significantly increased, while miR-150 decreased in LN (P > .05) patients as compared with healthy controls. Receiver operating characteristic (ROC) analysis indicated that miR-21 was superior in discriminating LN patients from controls with an Area Under Curve (AUC) of 0.912 [95% CI = 0.83 to 0.99, P < .001], whereas the multivariate ROC curve analysis revealed the high accuracy [AUC = 0.93, P < .001, 79% sensitivity and 83% specificity] of the miR-21, -150, and -423 to differentiate LN from controls. CONCLUSION: The involvement of the studied miRNAs in renal fibrosis and the obtained results make it rational to speculate that they may be used as potential biomarkers in LN.

Altered levels of immune-regulatory microRNAs in plasma samples of patients with lupus nephritis.

Introduction: Lupus nephritis (LN) is a major cause of mortality and morbidity in the patients with lupus, a chronic autoimmune disease. The role of genetic and epigenetic factors is emphasized in the pathogenesis of LN. The aim of the present study was to evaluate the levels of immune-regulatory microRNAs (e.g., miR-31, miR-125a, miR-142-3p, miR-146a, and miR-155) in plasma samples of patients with LN. Methods: In this study, 26 patients with LN and 26 healthy individuals were included. The plasma levels of the microRNAs were evaluated by a quantitative real-time PCR. Moreover, the correlation of circulating plasma microRNAs with disease activity and pathological findings along with their ability to distinguish patients with LN were assessed. Results: Plasma levels of miR-125a (P = 0.048), miR-146a (P = 0.005), and miR-155 (P< 0.001) were significantly higher in comparison between the cases and controls. The plasma level of miR-146a significantly correlated with the level of anti-double strand-DNA antibody and proteinuria. Moreover, there was a significant correlation between miR-142-3p levels and disease chronicity and activity index (P <0.05). The multivariate ROC curve analysis indicated the plasma circulating miR-125a, miR-142-3p, miR-146, and miR-155 together could discriminate most of the patients with LN from controls with area an under curve (AUC) of 0.89 [95% CI, 0.80-0.98, P<0.001], 88% sensitivity, and 78% specificity. Conclusion: Based on the findings of the present study, the studied microRNAs may be involved in the pathogenesis and development of LN and have the potential to be used as diagnostic and therapeutic markers in LN.

Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients.

BACKGROUND: The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. OBJECTIVE: The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin(®)) and compare it with the innovator product Eprex(®), as a standard rHuEPO. METHODS: One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80-120 IU/kg/week in 2-3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. RESULTS: A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p < 0.001). However, these factors were not significantly different between the groups, neither at baseline nor at the end of study (p > 0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. CONCLUSION: Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.

Risk factors of HCV seroconversion in hemodialysis patients in tabriz, iran.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant health concern in patients with end-stage renal disease under dialysis. Epidemiological studies have reported a prevalence rate of 5.5-55.9% for this condition in Iran. OBJECTIVES: We evaluated the risk factors for HCV infection and seroconversion in hemodialysis patients. PATIENTS AND METHODS: A retrospective analysis was performed on 455 hemodialysis patients from each of the five dialysis units in Tabriz, northwest Iran. Possible risk factors for HCV infection and seroconversion were evaluated. RESULTS: A total of 37 patients were HCV positive (8.1% of the study population) and seroconversion occurred in 18 of them during the dialysis treatment (3.95% of the study population). History of renal transplantation (44.4%, P < 0.0001), surgical intervention (except for renal transplantation and AV fistula placement) (94.4%, P = 0.03), and mean duration of dialysis (106.06 ± 55.519, P < 0.0001) had strong statistically significant associations with the seroconversion. CONCLUSIONS: The current study indicates increased risk for HCV infection in patients under dialysis and its relation with the mean duration of hemodialysis, history of renal transplantation and surgical intervention. Considering the immune deficiency in these patients, intense education to both patients and medical staff will be beneficial.

Relation between exhaled nitric oxide and left ventricular performance in chronic hemodialysis patients.

INTRODUCTION: End-stage renal disease is the most debilitating condition for patients with renal diseases. Cardiovascular disease is the leading cause of death in these patients. It has been shown that nitric oxide (NO) increases in renal failure and hemodialysis patients and could be correlated with cardiovascular diseases in this population. OBJECTIVES: To investigate the relation between exhaled nitric oxide (eNO) and left ventricular performance in chronic hemodialysis patients. METHODS: In this prospective study, eNO was measured in 20 chronic hemodialysis patients (13 males and 7 females with the mean age of 45.20 ± 14.99 years). Left ventricular findings were studied by conventional and Doppler echocardiography. eNO correlation with the echocardiographic parameters was evaluated. RESULTS: The median eNO was 11.65 ppb (range: 1.9-29.9 ppb). eNO was positively correlated with left ventricular ejection fraction (ρ = 0.561, p = 0.01) and negatively correlated with left ventricular end systolic volume (ρ = -0.451, p = 0.046), isovolumic relaxation time (ρ = -0.448, p = 0.047) and myocardial performance index (ρ = -0.587, p = 0.007). CONCLUSION: There is a positive correlation between eNO and left ventricular performance in chronic hemodialysis patients. Therefore, eNO may play an important role in pathophysiology of cardiac involvement in these patients.