The role of erythrocytes phosphatidylserine exposure in anemia in peritoneal dialysis patients

BACKGROUND: An increased red blood cell (RBC) phosphatidylserine (PS) exposure in uremic patients was found that could promote macrophage recognition and decrease RBC survival time. Furthermore, a reduced red cell life span was found to contribute anemia in patients with renal failure. It is therefore possible to hypothesize that increased PS externalization of RBC may influence renal anemia. The present study preliminarily explored the role of erythrocytes' PS exposure in anemia in uremic patients. METHOD: Erythrocyte PS exposure was measured in 67 stable patients on continuous ambulatory peritoneal dialysis (CAPD). An investigation was conducted in the relationship between the level of erythrocyte PS exposure and hemoglobin concentration. A flow-cytometric assay based on FITC-Annexin V was used to measure the PS exposure of erythrocytes. RESULTS: An inverse correlation was found between the percentage of PS-positive RBCs and hemoglobin concentration (r = -0.2601, p < 0.05). Logistic regression analysis revealed that the percentage of PS-positive RBCs was identified as a risk factor for anemia (Hazards ratio = -0.421, p < 0.05). CONCLUSION: This study found that elevated PS exposure in erythrocytes might be a risk factor for anemia and contribute to the development of anemia in peritoneal dialysis patients.     

Enhanced platelet apoptosis in chronic uremic patients

Background: There is a paucity of research on platelet apoptosis and its contribution to platelet dysfunction in uremic patients. The present study sought to analyze platelets apoptosis in uremic patients who underwent different dialysis modalities. Methods: Sixteen chronic uremic patients (5 on hemodialysis, 6 on peritoneal dialysis and 5 on non-dialysis) and 16 controls were studied. Platelet-rich plasma was detected for apoptotic events including depolarization of mitochondrial inner membrane potential (ΔΨm), phosphatidylserine (PS) exposure, activation of caspases-3 and Bcl-2 family proteins variations by Flow Cytometry or by Western-Blot. Washed normal platelets were incubated with normal or uremic platelet poor plasma and then were detected apoptotic events. Platelets function was assessed by ristocetin induced aggregative function test. Results: Compared to controls, uremic platelets demonstrated greater apoptosis for the ΔΨm depolarization (43.48?±?9.58 vs. 52.76?±?15.36, p?=?0.005) as well as PS exposure (1.36?±?0.51 vs. 0.99?±?0.27, p?0.001). There was no significant difference among different treatment groups (for the ΔΨm depolarization f?=?0.16, p?=?0.85; for the PS exposure f?=?1.06, p?=?0.36). Western Blot analyses showed caspase-3 activation and pro-apoptotic Bcl-2 family proteins expression. Platelets exposed to uremic plasma exhibited distinct apoptosis phenomena. Ristocetin induced platelet aggregation was markedly diminished in uremic patients and treated platelets. Conclusions: These findings indicate that platelets are incurred apoptosis in uremia patients. Uremic plasma accelerates apoptosis of normal platelets, resulting in a dysfunctional pattern of platelets in uremia. Uremic platelets apoptosis has no relationship with dialysis modality.     

Increased erythrocyte phosphatidylserine exposure in chronic renal failure.

The appearance of phosphatidylserine, an aminophospholipid normally confined to the inner monolayer, at the outer leaflet of red cell membrane may have several pathophysiologic implications. This study examines erythrocyte phosphatidylserine exposure in chronic renal failure (CRF) patients on conservative treatment or on dialysis, to assess possible alterations to phospholipid asymmetry in a condition associated with a state of deranged red cell function. A significant increase in phosphatidylserine-expressing erythrocytes was found in undialyzed patients with CRF (2.32%) and patients on hemodialysis (3.06%) and on peritoneal dialysis (2.14%) compared with control subjects (0.68%). In undialyzed CRF patients, a strong correlation (r = 0.903) was found between the percentage of phosphatidylserine-expressing red cells and the serum creatinine concentration. The increased exposure of phosphatidylserine in uremic erythrocytes may be due to inhibition of phosphatidylserine transport from the outer to the inner leaflet of plasma membrane and may promote an increased erythrophagocytosis. In reconstitution experiments, normal erythrocytes showed an increase in phosphatidylserine-expressing cells when incubated in uremic plasma (3.2% after 2 h versus 1.1% at beginning of incubation), whereas phosphatidylserine-positive uremic erythrocytes decreased when resuspended in normal plasma (2.03% after 2 h and 1.65% after 8 h versus 2.9% at beginning of incubation). Preliminary characterization of the putative uremic compound(s) indicates a molecular weight between 10,000 and 20,000, as well as heat instability. These findings show an impairment of erythrocyte membrane phospholipid asymmetry in CRF patients, regardless of the dialysis treatment. Such abnormality seems related to the uremic state and could contribute to the red cell pathology present in CRF.     

Erythrocyte susceptibility to oxidative stress in chronic renal failure patients under different substitutive treatments

An increased oxidative stress is now considered one of the major risk factors in chronic renal failure (CRF) patients that may be exacerbated by dialysis. It has been postulated that this increased oxidative stress might cause an augmented red blood cell (RBC) membrane lipid peroxidation with the consequent alteration in membrane deformability. The aim of this study was to evaluate RBC susceptibility to an in vitro induced oxidative stress and RBC antioxidant potential in different groups of CRF patients undergoing different substitutive treatment modalities. Fifteen end-stage CRF patients were evaluated in conservative treatment, 23 hemodialysis (HD) patients, 15 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 kidney transplanted patients, and 16 controls. Their RBCs were incubated with the oxidative stress-inducing agent tert-butylhydroperoxide both in the presence and in the absence of the catalase inhibitor sodium azide, and the level of malondialdehyde (MDA) (a product of lipid peroxidation), was measured at 0, 5, 10, 15, and 30 min of incubation. In addition, the RBC content of reduced glutathione (GSH) was measured by HPLC. As opposed to the controls, RBCs from end-stage CRF patients exhibited an increased sensitivity to oxidative stress induced in vitro, both in the absence and presence of a catalase inhibitor, as demonstrated by a significantly higher level of MDA production at all the incubation times (P < 0.05). Different substitutive treatments had different impacts on this phenomenon; CAPD and kidney transplantation were able to normalize this alteration while HD was not. GSH appeared to be related to the increase in RBC susceptibility to oxidative stress; its content being significantly elevated in end-stage CRF and HD patients as compared with CAPD and transplanted patients and controls (P < 0.05). No significant changes were observed in the RBC glutathione content during the HD session. The increase of GSH in RBCs of end-stage CRF and HD patients seems to indicate the existence of an adaptive mechanism under increased oxidative stress occurring in vivo. Unlike HD, the beneficial effect of CAPD on the anemia of dialysis patients might partly be due to a condition of lower oxidative stress that might in addition counterbalance the cardiovascular negative effects of dislipidemia of CAPD patients.     

Early erythropoietin reduced the need for red blood cell transfusion in childhood hemolytic uremic syndrome—a randomized prospective pilot trial

Childhood hemolytic uremic syndrome (HUS) is most often caused by enterohemorrhagic Escherichia coli (EHEC). Due to severe hemolysis, red blood cell (RBC) transfusions are often necessary, and anemia is aggravated by low erythropoietin (EPO) levels caused by acute renal failure. In a single center, prospective study, we randomized ten children with EHEC-positive HUS into two therapeutic groups: one receiving EPO treatment (median age 2 years, age range 1–3 years) and the other receiving standard therapy (median age 2 years, age range 1–6 years). Red blood cell transfusions were performed when the hemoglobin level (Hb) fell below 5 mg/dl. The number of RBC transfusions was compared in both groups. The Hb level at admission was comparable between both groups (6.4 vs. 8.1 mg/dl, P > 0.05, t-test). However, children in the EPO group required a significantly lower mean number of RBCs than those in the non-EPO group (0.2 vs. 1.4, P < 0.04, t-test). Based on these results, we suggest that the early administration of EPO at the time of hemolytic anemia and beginning renal failure may attenuate renal anemia in children with EHEC-induced HUS and thereby reduce the number of RBC transfusions required. The results of this pilot study will have to be confirmed in a larger multicenter trial.     

The Red Blood Cell Deformability in Patients Suffering from End Stage Renal Failure on Hemodialysis or Continuous Ambulatory Peritoneal Dialysis

Anemia is the main problem for patients suffering from end stage renal disease (ESRD). This study aimed to determine whether the index of rigidity (IR), that shows red blood cells (RBCs) deformability and the possible IR disturbances can provide an explanation about the cause of anemia, in patients undergoing maintenance hemodialysis (HD) or on peritoneal dialysis. The IR was determined in 39 hemodialyzed patients, who were already in dialysis for a period of time ranging from 16 to 120 months (mean ± SD = 41.8 ± 24.1) (Group A). Furthermore, the IR was measured in 32 patients on continuous ambulatory peritoneal dialysis (CAPD), who were in CAPD for a period of time ranging from 6 to 60 months (mean ± SD = 10.7 ± 9.9) (Group B). Finally, the IR was determined in 17 normal individuals (group C). The RBCs IR was measured twice in group A (before and after the end of a hemodialysis session) and once in groups B and C. The IR was determined by hemorrheometry (method of filtration), using special equipment. In group A the IR was increased in comparison to the control group (C) (17.9 ± 6.2 vs. 10.2 ± 1.8, p < 0.0001). This increase was even higher in the measurement at the end of the hemodialysis session (paired t‐test, p < 0.0001). The RBCs IR in CAPD patients was significantly lower than that of HD patients (12 ± 3.8 vs. 17.9 ± 6.2, p < 0.0001) and was not statistically different from the control group (12 ± 3.8 vs. 10.2 ± 1.8, p = 0.068). It is concluded from the study that: 1) in HD patients occur disturbances in the deformability of the RBCs, that are worsened by the hemodialysis session; 2) the index of rigidity of RBCs is significantly higher in the HD patients than in CAPD patients; 3) in patients on CAPD, the disturbance of deformability of the RBCs was less in comparison to the control group, which however does not reach the statistically significant levels.     

Folic acid status of patients with chronic renal failure maintained by dialysis

Twenty-five uremic patients on chronic hemodialysis were followed over a period of 9 months with regard to hemoglobin, mean corpuscular volume and folate concentration in serum and erythrocytes. The daily dietary intake of folic acid was estimated at 80-90 microgram, and no folic acid supplements were given. None of the patients developed macrocytic anemia. At the end of the period all patients had a normal erythrocyte folate content. Serum folate was normal in 17 and below normal in 8 patients. These 8 patients were in a negative folate balance at the time of investigation. In 7 patients dialyzed with a RP VI dialyzer the maximum loss of folic acid was 75 microgram/dialysis, and in 6 patients on chronic intermittent peritoneal dialysis the maximum loss was 13 microgram/dialysis. Thus there is no need for oral folic acid supplementation in uremic patients on chronic dialysis provided that daily dietary intake of folic acid is adequate.     

CYANATE AS A HEMOLYTIC FACTOR

During advanced renal failure, and particularly in patients with end-stage renal disease, proteins are carbamylated as a result of a reaction with cyanate. If the carbamylation of proteins adversely alters their biologic activities and structures, then urea must be viewed as an uremic toxin, rather than a surrogate. Therefore, we studied in this paper the role of cyanate as a hemolytic factor of erythrocytes to explain anemia observed in patients with high blood urea levels due to inadequate dialysis. Cyanate was added to make the final concentration 150, 300 and 600 nmol to each test tube containing the final concentration of 140×10⁶ with human erythrocytes per mL of phosphate buffered saline solution. And they were incubated at 37°C for 24, 48 and 72 hours. The extent of hemolysis and carbamylation was monitored. The levels of hemolysis and carbamylated erythrocytes increase as the time of exposure to cyanate increased from 24 hours to 72 hours. Furthermore, those increased as cyanate concentration in the incubation media rose from 150 nmol to 600 nmol. Cyanate can induce hemolysis by carbamylation of erythrocytes. Urea, through cyanate, may contribute to hemolysis. If one extrapolates these results to patients with end-stage renal disease, it may help explain one of the reasons for the anemia in patients with high levels of BUN due to inadequate dialysis.     

Elevation of levels of carcinogenic tryptophan pyrolysis products in plasma and red blood cells of patients with uremia.

The carcinogenic tryptophan pyrolysis products, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), have been measured in plasma and red blood cells (RBC) of patients with uremia and normal subjects by using a high-performance liquid chromatography (HPLC) method. In both uremic patients and normal subjects, these carcinogens have been detected in RBC as well as plasma. Trp-P-1 and Trp-P-2 levels in plasma of uremic patients were significantly higher than those of normal subjects. Moreover, these carcinogen levels in RBC (per hemoglobin) were significantly elevated in uremic patients in spite of the presence of severe anemia. These results suggest that patients with uremia are continuously exposed to higher levels of these carcinogens as compared with normal subjects. Our data also support the idea that these carcinogens in plasma and RBC are suitable for monitoring exposure levels in humans.     

EFFECT OF DIALYSIS ON ERYTHROCYTE MEMBRANE OF CHRONICALLY HEMODIALYZED PATIENTS

The present work examines the role of uremia and the effect of dialysis treatment on red blood cells (RBCs) membrane properties of hemodialysis patients. The results showed that, the uremic patients had a lower values of erythrocyte deformability than that of healthy control subject. The median osmotic fragility (MOF) showed a significant increase in hemodialyzed patients than that for control group. The osmotic resistance to hemolysis was improved after dialysis. The solubilization process of the RBCs membrane showed that the detergent concentration needed to solubilize the RBCs membrane for uremic patient was much higher than that for control group. The abnormalities of the present results for RBCs membrane properties are mostly related to membrane fluidity, which are slightly improved after dialysis. Biochemical analysis showed a decreasing trend in RBCs count, urea nitrogen, creatinine, potassium, phosphate, hemoglobin, and serum osmolarity after dialysis. Moreover, serum sodium, ionized calcium, total calcium, and blood sugar, showed a significant increase after dialysis.     

Red blood cell lifespan in long-term hemodialysis patients treated with roxadustat or recombinant human erythropoietin

IntroductionA significant decrease in red blood cell (RBC) survival has been observed in patients with renal failure, which is supposed to contribute to renal anemia. The aim of this observational study was to determine RBC survival in hemodialysis (HD) patients treated with roxadustat or recombinant human erythropoietin (rhuEPO) compared with healthy persons.MethodsRBC lifespan was measured by Levitt’s CO breath test with newly developed automatic instrument ELS Tester.ResultsA total of 102 patients receiving long-term HD from two independent dialysis centers enrolled in the study, of whom 62 were treated with rhuEPO and 40 were on roxadustat therapy. A total of 25 healthy participants were recruited to match HD participants according to age and sex. Median RBC survival times in rhuEPO, roxadustat, and control groups were 65.0 (25th–75th percentile, 49.5–77.3), 75.5 (25th–75th percentile, 57.3–99.3), and 108.0 (25th–75th percentile, 89.0–141.5) d, respectively. Patients treated with roxadustat had significantly longer RBC survival time than patients treated with rhuEPO (p < .05). In multivariate analysis of factors affecting RBC lifespan in the whole HD patients, anemia treatment drugs (rhuEPO/roxadustat) and levels of hemoglobin were the significantly independent factors. RBC survival was not found to correlate with either weekly rhuEPO dosage (r = –0.087, p = .500) or weekly roxadustat dosage (r = −0.267, p = .110) in our cohort.ConclusionsHD patients treated with roxadustat had significantly longer RBC survival time than patients treated with rhuEPO, large prospective studies with long-term follow-up are warranted to verify the results in future. Abbreviations RBC: red blood cell; HD: hemodialysis; rhu EPO: recombinant human erythropoietin; ESRD: end-stage renal disease; EPO: erythropoietin; ROS: reactive oxygen species; CKD: chronic kideny disease; ESAs: erythropoiesis-stimulating agents; HIF-PHD: hypoxia-inducible factor prolyl hydroxylase; CO: carbon monoxide; Hb: hemoglobin     

Effect of peritoneal dialysis versus hemodialysis on renal anemia in renal in end-stage disease patients: a meta-analysis

The aim of this meta-analysis was to evaluate the effect of peritoneal dialysis (PD) and hemodialysis (HD) on renal anemia (RA) in renal disease patients by a meta-analysis. Relevant studies published before June 2015 were searched. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the effect of HD and PD on RA based on five indexes: hemoglobin, ferritin, transferrin saturation index, serum albumin, and parathyroid hormone. Sensitivity analysis and publication bias assessment were conducted to evaluate the stability and reliability of our results. A total of fourteen eligible studies with 1103 cases underwent HD and 625 cases underwent PD were used for this meta-analysis. There were no significant difference for levels of hemoglobin (SMD?=??0.23, 95% CI: ?0.74 to 0.28), ferritin (SMD?=?0.01, 95% CI: ?0.59 to 0.62), parathyroid hormone (SMD?=?0.11, 95% CI: ?1.53 to 1.75) and transferrin saturation index (SMD?=??0.06, 95% CI: ?0.67 to 0.56) between HD and PD group. However, the content of serum albumin in HD group was much more than that in PD group (SMD?=?1.58, 95% CI: 0.35 to 2.81). Neither of the included studies could reverse the pooled side effect and Egger’s test demonstrated no publication bias. Both of the two dialysis strategies have a similar effect on RA in renal disease patients.     

Pulmonary Hypertension in Dialysis Patients

Cardiovascular complications are encountered frequently in end-stage renal disease (ESRD) patients. The study was designed as a prospective cohort study and a total of 105 dialysis patients, 77 hemodialysis and 28 peritoneal dialysis patients, were investigated. All patients had undergone M-Mode Doppler echocardiography every 6 months by which their systolic pulmonary arterial pressures (sPAPs) and left ventricular mass indices (LVMIs) were recorded. Thirty-nine (37.1%) patients had pulmonary hypertension (PHT), that is, a mean sPAP of more than 35 mmHg. The frequency of PHT was higher in peritoneal dialysis patients but the difference was insignificant (p = 0.08). However, the frequency of left ventricular hypertrophy (LVH) was found to be significantly higher in peritoneal dialysis patients than in hemodialysis patients (p = 0.001). When patients with and without PHT were compared, the duration of dialysis (p = 0.02), hemoglobin (p = 0.01), HbA1c (p = 0.03), and serum albumin levels (p = 0.003) were found to be significantly higher in patients with PHT than those without PHT. In conclusion, although nonsignificant, we found a higher prevalence of PHT in peritoneal dialysis patients when compared with hemodialysis patients. This might be due to the significantly higher prevalence of LVH, hence hypervolemia, in peritoneal dialysis patients. The prevention and treatment of PHT in dialysis patients is very important for the improvement of survival in these patients. Hence, the increased prevalence of PHT in ESRD patients necessitates understanding the multiple and interacting factors, such as LVH, serum albumin and hemoglobin levels, and control of diabetes, that might contribute to this pathology in these patients.     

Reduced superoxide dismutase activity in erythrocytes of dialysis patients: a possible factor in the etiology of uremic anemia

Superoxide dismutase (SOD) plays a major part in the destruction of oxygen-free radicals in the body. SOD activity is impaired by several trace elements including aluminium and silicon which are found in increased levels in plasma and tissues of uremic man. SOD activity was investigated in the erythrocytes of normal controls and of dialysis patients to determine if lack of SOD-protective activity could be a contributory cause to the increased hemolysis of uremia. It was found that SOD levels in red cell hemolysate were significantly lower in dialysis patients (41.4 +/- 9.1 units/100 ml) compared to control (49.3 +/- 7.2 units/100 ml) (U = 7.3; p less than 0.005). When expressed per 100 ml of whole blood SOD levels were 3.25 +/- 0.93 units/100 ml in dialysis patients and 6.46 +/- 0.99 units/100 ml in controls (U = 96; p less than 0.001). It is concluded that inhibition of SOD activity in the erythrocytes of dialysis patients may contribute to their anemia.     

Relation Between Echinocytosis and Erythrocyte Calcium Content in Hemodialyzed Uremic Patients

A rise in intracellular calcium concentration in erythrocytes has multiple effects on these cells. The purpose of this study was to determine the changes of calcium content in red blood cells (RBCs) and of echinocyte percentages in uremic patients during hemodialysis sessions. In 30 uremic patients under hemodialysis, the calcium content of RBCs and echinocyte percentages were determined in 3 blood samples collected at 0 min hemodialysis (prehemodialysis), 45 min hemodialysis, and 240 min hemodialysis (end hemodialysis) for a 4 h hemodialysis session. Calcium content of RBCs and echinocytes were also determined in 22 normal subjects (controls). The findings of the present study were that the mean values (+/-SD) of calcium content of RBCs in patients at 0 min hemodialysis, 45 min hemodialysis, and 240 min hemodialysis were 2.00 +/- 1.0, 2.66 +/- 0.87, and 1.62 +/- 0.66 microg/ml respectively and 0.65 +/- 0.07 microg/ml in controls. These values show that the calcium content of RBCs in uremic patients at 0 min hemodialysis, 45 min hemodialysis, and 240 hemodialysis was significantly higher than in controls (p < 0.0001), and that RBC calcium content at 45 min hemodialysis was significantly higher in comparison to that at 0 min hemodialysis (p < 0.001) and to that at 240 min hemodialysis (p < 0.0001), while that at 240 min hemodialysis was significantly lower than at 0 min hemodialysis (p < 0.05). The mean values (+/-SD) of echinocyte percentages in patients at 0 min hemodialysis, 45 min hemodialysis, and 240 hemodialysis were 11.93 +/- 6.18, 17.23 +/- 4.1, and 7.96 +/- 5.67% respectively, and in controls ranged from 0 to 1%. The values in uremic patients show a transient increase of echinocyte percentages at 45 min hemodialysis, which is significant in comparison to that at 0 min hemodialysis (p < 0.001) and to that at 240 min hemodialysis (p < 0.0001). Echinocyte percentages at 240 min hemodialysis were significantly lower to those at 0 min hemodialysis (p < 0.001). Correlation between calcium content of erythrocytes and echinocyte percentages shows a significantly positive relationship at 45 min hemodialysis (r = 0.368, p < 0.05) but no significant relationship at 0 min hemodialysis and 240 min hemodialysis. In conclusion, uremic patients under hemodialysis present with high calcium content in erythrocytes and abnormal erythrocytes like echinocytes. A rapid and transient increase of erythrocyte calcium is also accompanied by transient elevation of echinocytes in the first hour of hemodialysis (45 min hemodialysis), which returns after hemodialysis to lower than prehemodialysis levels.     

Anemia and red blood cell transfusion in the critically ill

Critically ill patients are anemic early in their intensive care unit (ICU) course. As a consequence of this anemia they receive a large number of red blood cell (RBC) transfusions. There is little evidence that "routine" transfusion of stored allogeneic RBCs is beneficial to critically ill patients and may in fact be associated with worse clinical outcomes. It is clear that most critically ill patients can tolerate hemoglobin levels as low as 7 g/dl and therefore a more conservative approach to RBC transfusion is warranted. Strategies to minimize loss of blood and increase the production of RBCs are also important in the management of all critically ill patients.     

Low whole blood and erythrocyte levels of glutathione in hemodialysis and peritoneal dialysis patients

Dialysis patients are reported to have impaired antioxidant mechanisms, including those involving glutathione-dependent enzymes. This study used high-performance liquid chromatography assays that directly measure total (oxidized + reduced) glutathione and its precursor cysteine (CYS) to compare the whole blood of hemodialysis (prehemodialysis and posthemodialysis) and peritoneal dialysis patients to that of blood donors with no known kidney disease (n = 20 in each group). The levels in erythrocytes were calculated from that data (as nmol/g hemoglobin) because these cells are the major compartment of blood glutathione and their survival may be shortened by oxidant damage. Both dialysis groups had significantly (P = 0.0001) higher CYS levels in the plasma compartment than the controls (251 nmol/mL), with prehemodialysis levels (432 nmol/mL) being greater than peritoneal dialysis levels (334 nmol/mL). Hemodialysis acutely lowered CYS levels (215 nmol/mL) below those of controls. Expressed per milliliter whole blood, both dialysis groups had significantly (P = 0.0001) lower glutathione levels than controls (1,276 nmol/mL), with prehemodialysis and peritoneal dialysis levels being similar (778 and 912 nmol/mL). Values increased prehemodialysis to posthemodialysis, consistent with hemoconcentration. Expressed per gram hemoglobin, the dialysis groups had significantly (P < 0.015) lower glutathione levels than the controls (8,938 nmol/g hemoglobin), with similar prehemodialysis, posthemodialysis, and peritoneal dialysis values (7,207, 7,315, and 7,915 nmol/g hemoglobin, respectively). In summary, hemodialysis and peritoneal dialysis patients are at increased risk from oxidative stress due to glutathione deficiency in whole blood and erythrocytes.     

Lack of relation between serum parathyroid hormone levels and erythrocyte osmotic fragility in pediatric patients on peritoneal dialysis

Secondary hyperparathyroidism and anemia are the hallmarks in uremic patients. It is suggested that parathyroid hormone increases erythrocyte osmotic fragility and induces hemolysis. The present study was undertaken to examine the possible relationship between erythrocyte osmotic fragility and secondary hyperparathyroidism in 20 pediatric patients on maintenance peritoneal dialysis. We found that erythrocyte osmotic fragility in these patients was normal. No correlation between erythrocyte osmotic fragility and hematochemical changes associated with secondary hyperparathyroidism was found. We conclude that erythrocyte osmotic fragility was normal in pediatric patients on peritoneal dialysis and excess parathyroid hormone levels do not affect erythrocyte osmotic fragility and do not cause anemia.     

A circulating inhibitor of the RBC membrane calcium pump in chronic renal failure.

A humoral inhibitor of the membrane calcium pump was studied in plasma from 28 normal controls, 33 patients receiving long-term hemodialysis, and 26 with chronic renal failure (CRF; creatinine clearance range was 6 to 97 ml/min). Calcium pump activity was measured as the rate of Sr2+ efflux in normal erythrocytes (RBCs) loaded with Sr2+ (a substitute of Ca2+ in the calcium pump). Plasma, and plasma ultrafiltrates from hemodialysis patients strongly inhibited calcium pump activity compared with controls without plasma (36 +/- 18 vs. 25 +/- 12, %INHIBITION/CONTROL, P < 0.05). Inhibition markedly decreased with acute hemodialysis (16 +/- 12 vs. 5 +/- 14, %INHIBITION/NORMAL PLASMA, N = 15, P < 0.001). In CRF, degree of inhibition correlated with the serum creatinine concentration (r = 0.75, P < 0.001). A kinetic study showed that plasma decreased the maximal rate of the Ca2+ pumps (Vmax) without affecting the apparent affinity for internal cations (KSr). Moreover, the plasma inhibitory factor had a low molecular weight, and was dialyzable and heat stable. In conclusion, we found evidence for an RBC membrane calcium pump inhibitor in uremic plasma, which correlates with the degree of renal insufficiency. Possibly, it may increase calcium content in RBCs and other cells and could thus be related to uremic toxicity and/or hypertension.