scholarly journals Chronic Kidney Disease Predicts Impaired Membrane Microviscosity of Red Blood Cells in Hypertensive and Normotensive Subjects

2013 ◽  
Vol 54 (3) ◽  
pp. 154-159 ◽  
Author(s):  
Kazushi Tsuda
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Membrane Microviscosity ◽  
Normotensive Subjects

scholarly journals Erythrogram Patterns in Dogs with Chronic Kidney Disease

2021 ◽  
Vol 8 (7) ◽  
pp. 123
Author(s):  
Ilaria Lippi ◽  
Francesca Perondi ◽  
George Lubas ◽  
Eleonora Gori ◽  
Alessio Pierini ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Common Finding ◽  
Severe Condition ◽  
Regeneration Rate ◽  
Morphological Abnormalities ◽  
Morphological Alterations ◽  
Frequent Finding

Anemia is considered a common finding in dogs with chronic kidney disease (CKD), typically as normochromic, normocytic, and non-regenerative. Although anemia can occur at any CKD IRIS (International Renal Interest Society) stage, its severity is related with the loss of kidney function. The aim of the present study was to retrospectively evaluate quantitative and morphological abnormalities of the erythrogram in dogs at different CKD IRIS stages. A total of 482 CBCs from 3648 initially screened were included in the study. Anemia was present in 302/482 (63%) dogs, in the majority of which it was normochromic, normocytic, and non-regenerative (295/302; 98%). The number of reticulocytes was <60,000/μL in the majority of dogs (248/295; 84%), with a correlation between poor regeneration rate and progression of CKD (p = 0.0001). The frequency of anemia significantly differed (p = 0.0001) among the IRIS stages: 108/231 (47%) in IRIS 2, 77/109 (71%) in IRIS 3, and 117/142 (82%) in IRIS 4. Dogs at IRIS stages 3 and 4 were more likely to have moderate to severe anemia, compared to dogs at IRIS stage 2 (p = 0.0001). Anisocytosis was the most frequent morphological abnormality (291/482; 60%), whereas the presence of poikilocytosis showed an association with progression of IRIS stages (p = 0.009). Among different morphological abnormalities, the frequency of fragmented red blood cells and Howell–Jolly bodies showed a significant association with the progression of CKD. Anemia was a frequent finding in CKD dogs, mostly associated with none to poor regeneration rate. Similar to human medicine, advanced CKD stages are more frequently characterized by morphological alterations, such as fragmented red blood cells and Howell–Jolly bodies, which may suggest a more severe condition of reduced bone marrow activity and microangiopathy.

ACE-536, a Modified Type II Activin Receptor Increases Red Blood Cells In Vivo by Promoting Maturation of Late Stage Erythroblasts

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4236-4236 ◽  
Author(s):  
Rajasekhar NVS Suragani ◽  
Samuel M. Cadena ◽  
Dianne Mitchell ◽  
Dianne Sako ◽  
Monique Davies ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Kidney Disease ◽  
Red Blood Cells ◽  
Late Stage ◽  
Blood Cells ◽  
Treated Group ◽  
Activin A ◽  
Vehicle Group ◽  
Type I

Abstract Abstract 4236 Anemia is one of the most common blood disorders in several diseases including cancer, heart failure, chronic kidney disease (CKD) and Myeloid Dysplastic Syndromes (MDS) associated with a negative outcome. Administration of recombinant Erythropoietin (EPO) represents the most common treatment for anemia. However, a significant number of people remain hypo or non-responsive to EPO treatment, and in some cases its use has been linked to tumor growth, cardiovascular disease and poorer survival. The members of TGFβ super family of ligands (Activins, GDFs and BMPs) and receptors (Type I and II) regulate more than 500 target genes transcriptionally by Smad phosphorylation and are involved in many cellular functions including cell growth, adhesion, migration, differentiation and apoptosis in a concentration and context dependent manner. Members of the TGFβ family have also demonstrated a role in erythropoiesis. ACE-536, a non-ESA agent is a soluble human Fc fusion chimera of a modified Activin Type IIb receptor with a mutation in its extracellular domain. Surface Plasmon Analysis (Biacore) analysis and cell based reporter assays revealed that this mutation disrupted its binding to Activin A but not to GDF11 or GDF8. ACE-536 acts as a decoy receptor for TGFβ signaling and demonstrated potent increase in red blood cells in all the tested animals (mice, rats and monkeys). Subcutaneous administration of ACE-536 (10mg/kg) to C57BL/6 mice resulted in a significant increase in hematocrit, hemoglobin and red blood cells (RBC) over the TBS treated vehicle group after 4 days. These observations were seen even in the presence of an EPO neutralizing antibody; suggesting that EPO is not directing the initial RBC response to ACE-536 treatment. There were no increase in BFU-E or CFU-E colony formation from bone marrow and spleen after 48hrs treatment with ACE-536 over TBS treated group demonstrating that it does not have effect on erythroid progenitor population. Differentiation profiling of bone marrow and splenic erythroblasts by flow cytometric analysis revealed that ACE-536 promotes maturation of developing erythroblasts. ACE-536 treatment for 72 hours resulted in a decrease in basophilic erythroblasts and an increase in late stage poly, ortho chromatophilic erythroblasts in bone marrow and spleen compared to the TBS treated mice. Treatment of Sprague-Dawley rats with a murine analogue of ACE-536 (RAP-536; 10mg/kg) increased the reticulocyte formation in peripheral blood over vehicle treated group. ACE-536 (10mg/kg) treatment combined with recombinant human EPO (1800 units/kg) for 72 hours increased RBC, hematocrit and hemoglobin by approximately 23% over TBS treated vehicle group and 12% over EPO treatment alone. Consistent with its role in proliferation, EPO increased splenic basophilic erythroblast formation. However, ACE-536 treatment combined with EPO significantly promoted maturation of late stage erythroblasts; demonstrating a novel mechanism during erythroid differentiation. To gain further insights into its mechanism of action, C57BL/6 mice were administered with or without RAP-536 (10mg/ml twice a week) pre treated for a week with neutralizing anti-Activin A (10mg/kg) or ActRIIa (10mg/ml) or ActRIIb (10mg/ml) (does not bind ACE-536) antibodies. Anti-ActRIIa but not anti-Activin A or anti- ActRIIb antibody pre-treatment inhibited the RBC increase by RAP-536 suggesting that ActRIIa or its ligands are necessary for transducing the signal. To summarize, ACE-536 treatment results in a rapid increase in red blood cells by a novel mechanism promoting maturation of late stage erythroblasts. The efficacy of ACE-536 molecule was tested in several acute and chronic anemia animal models including blood loss anemia, chemotherapy induced anemia, chronic kidney disease (5/6 Nephrectomy) and Myeloid Dysplastic Syndrome (MDS) and found that ACE-536 treatment prevents or decreases anemia in all these models. Furthermore, unlike EPO, ACE-536 did not promote tumor progression (in Lewis Lung Carcinoma model) thus offering strong promise as alternate treatments for anemia. Disclosures: Suragani: Acceleron Pharma: Employment. Cadena:Acceleron Pharma: Employment. Mitchell:Acceleron Pharma: Employment. Sako:Acceleron Pharma: Employment. Davies:Acceleron Pharma: Employment. Tomkinson:Acceleron Pharma: Employment. Devine:Acceleron Pharma: Employment. Ucran:Acceleron Pharma: Employment. Grinberg:Acceleron Pharma: Employment. Underwood:Acceleron Pharma: Employment. Pearsall:Acceleron Pharma: Employment. Seehra:Acceleron Pharma: Employment. Kumar:Acceleron Pharma: Employment.

Structural-functional state of erythrocytes in children with chronic kidney disease

2019 ◽  
Vol 1 (7) ◽  
pp. 105-108
Author(s):  
A. V. Sabirova ◽  
D. K. Volosnikov ◽  
O. V. Matyash
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Red Blood Cells ◽  
Functional State ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Early Stage ◽  
Control Group ◽  
Healthy Children ◽  
Range Analysis

During Chronic Kidney Disease (CKD) development and progression emphasis is placed on structural-functional state of red blood cells. The aim of this paper is to examine red blood values and red blood cells morphological type in peripheral blood among children with CKD. 75 children with CKD aged 5-16 years were examined. The control group consisted of 25 healthy children of the same age range. Analysis of the morphometric parameters of red peripheral blood cells - mean volume (MCV) and erythrocyte diameter, mean content (MCH) and mean hemoglobin concentration in the erythrocyte (MCHC), were performed using a Gobas Micros (Roche) hematology counter. Smears were marked according to Romanovsky-Giemsa. Morphometric studies of red blood cells were carried out using the Morphology 5.2 program and red blood cell confocal microscopy on a LSM-710 Confocal Microscope, manufactured by Carl Zeiss. The tendency to poikilocytosis in CKD was confirmed. We identified that among children with CKD the distribution of red blood cells in diameter is disturbed, the content of microcytes increases, poikilocytosis is observed with an increase in the content of irreversibly transformed elements. The revealed features may serve as an additional criterion for the diagnosis of chronic kidney insufficiency at the early stage.

Abstract 11697: Hyperhomocysteinemia Induces CD40 + Monocyte and Inflammatory Monocyte in Chronic Kidney Disease Subjects via DNA Hypomethylation-Related Mechanism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jiyeon Yang ◽  
Abhigna C Kolli ◽  
Eric T Choi ◽  
Xiao-Feng Yang ◽  
Hong Wang
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Cells ◽  
Healthy Donor ◽  
Methylation Status ◽  
Phenotypic Characterization ◽  
Dna Hypomethylation ◽  
Rt Pcr ◽  
Inflammatory Monocyte ◽  
Cd40 Expression

Hyperhomocysteinenia (HHcy) is associated with chronic kidney disease (CKD) which has increased cardiovascular disease (CVD) mortality and mobility. Elevated inflammatory monocyte (inf. MC) is a cellular hallmark of chronic inflammation which contributes to the burden CVD. We previously reported that HHcy induces inf. MC differentiation in mice and DNA hypomethylation in vascular cells. We assesses whether HHcy causes MC differentiation in CKD and the underlying mechanism. Degree of CKD was determined by plasma creatinine from patients with peripheral vascular disease (VD). Estimated glomerular filtration rate was calculated with modification in age, race and gender. (VD, n=13; VD with CKD, n=13; Healthy donor without evidence of VD and CKD, n=13). Blood cells were assessed for phenotypic characterization by flow cytometry. We found that plasma Hcy levels are elevated in VD and CKD. CD14++CD16+ inf. MC are increased in VD subjects and mild HHcy(>15μM). Plasma Hcy levels are positively correlated with inf. MC, CD40, TNF receptor family 5. We identify that CKD patient serum and Hcy (50μM) treatment increased CD40 in purified human blood MC by RT-PCR. Hcy metabolites, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), are increased in CKD subjects. SAM/SAH ratio, an indicator of methylation status, is reduced and is negatively correlated with Hcy, inf. MC, and CD40+ inf. MC. Hcy induced MC-origin inflammatory cytokines IL-6 mRNA in MC isolated from healthy donor by RT-PCR, and potentiated inflammatory cytokine IL-6, TNFα, and IFN[[Unable to Display Character: &#612;]]-induced CD40 expression in cultured PBMCs. Hcy suppressed CD40 transcription and reduced DNA methyltransferase 1 protein levels in cultured human MC. We identified four DNA hypomethylation CpG dinucleotides at p65 and PU.1 transcription factor consensus sequences on CD40 promoter in white blood cells isolated from CKD patients by Bisulfite pyrosequencing. Finally, CD40L levels are positively correlated with plasma Hcy and inf. MC. CD40 ligation by CD40L treatment (0.4μg/l) in peripheral blood mononuclear cells (PBMC) induced inf. MC differentiation. We conclude that HHcy potentiates IFN[[Unable to Display Character: &#612;]]-mediated CD40 expression via CD40 DNA hypomethylation in CKD and promotes CD40-CD40L mediated inf. MC differentiation.

scholarly journals Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis

2020 ◽  
Vol 21 (21) ◽  
pp. 8131
Author(s):  
Deepika Watts ◽  
Diana Gaete ◽  
Diego Rodriguez ◽  
David Hoogewijs ◽  
Martina Rauner ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Iron Metabolism ◽  
Blood Cells ◽  
Hypoxia Inducible Factor ◽  
Altered Expression ◽  
Master Regulators ◽  
Complex Process

Erythropoiesis is a complex process driving the production of red blood cells. During homeostasis, adult erythropoiesis takes place in the bone marrow and is tightly controlled by erythropoietin (EPO), a central hormone mainly produced in renal EPO-producing cells. The expression of EPO is strictly regulated by local changes in oxygen partial pressure (pO2) as under-deprived oxygen (hypoxia); the transcription factor hypoxia-inducible factor-2 induces EPO. However, erythropoiesis regulation extends beyond the well-established hypoxia-inducible factor (HIF)–EPO axis and involves processes modulated by other hypoxia pathway proteins (HPPs), including proteins involved in iron metabolism. The importance of a number of these factors is evident as their altered expression has been associated with various anemia-related disorders, including chronic kidney disease. Eventually, our emerging understanding of HPPs and their regulatory feedback will be instrumental in developing specific therapies for anemic patients and beyond.

scholarly journals THE CONTENTS OF SCD40 AND INDICATORS OF DAMAGED ENDOTHELIUM IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2017 ◽  
pp. 57-69
Author(s):  
I. I. Topchii ◽  
А. N. Kirienko ◽  
M. M. Dunaevskaya ◽  
Е. N. Schenyavskaya ◽  
I. T. Birukova
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Cells ◽  
Standard Therapy ◽  
Immune Status ◽  
White Blood Cells ◽  
Endothelial Damage ◽  
Control Group ◽  
Chronic Glomerulonephritis ◽  
Compensatory Mechanism

Introduction. Impairments of endothelial structure and functions of renal vessels are regarded as important factors of progression and chronization of chronic kidney disease (CKD). It is well known that the CD40/CD40L interaction is responsible for the aggregation of blood cells and their adhesion to the vascular wall, as well as its effect on the state of immune response. We investigated whether this interaction could be altered in patients with CKD and impaired immune status. Materials and methods. We examined 48 patients with chronic glomerulonephritis (CGN), 38 patients with chronic pyelonephritis and 42 patients with essential hypertension (EH) - control group. All patients received standard therapy with an ACE inhibitor perindopril in combination with a calcium channel  antagonist amlodipine. Along with standard therapy the patients intravenously administered injections of "Kardioarginine." The degree of endothelial damage was assessed by the number of CEC and VE-cadherin content in blood plasma. In order to estimate changes in the immune status we determined the content of sCD40 in serum. Results. Increase in the content of serum sCD40 was shown for the CGN patients compared with healthy subjects and EH patients. The level of sCD40 in serum correlated with the number of CEC and VE-cadherin content in plasma. The use of kardioarginine combined with standard therapy led to reduction of sCD40 and stabilized the structure of endothelium. The loss of endothelial integrity in patients with CKD is apparently due to the activation of apoptosis with subsequent accelerated desquamation under the influence of activated white blood cells and the system of cytokines. Conclusions. The increase of sCD40 in patients with CKD may be a compensatory mechanism aimed to reduce the inflammatory activity by blocking the CD40/CD40L interaction at the cellular level.

scholarly journals A hepcidin lowering agent mobilizes iron for incorporation into red blood cells in an adenine-induced kidney disease model of anemia in rats

2013 ◽  
Vol 28 (7) ◽  
pp. 1733-1743 ◽  
Author(s):  
Chia Chi Sun ◽  
Valentina Vaja ◽  
Shanzhuo Chen ◽  
Igor Theurl ◽  
Aaron Stepanek ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Disease Model
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