Low Ca2+ dialysate. Effects on bone metabolism in the course of paired filtration dialysis

To evaluate the 1-year effects of PFD performed with low Ca2+ dialysate (1 mmol/l) on calcium metabolism and on bone disease, the authors studied in eight patients who were previously treated with PFD performed with standard Ca2+ dialysate (1.75 mmol/l). On samples from these subjects, the following were evaluated: 1) serum Ca2+ and PO4 levels, 2) serum PTH levels, 3) serum Al levels, and 4) bone morphology. All the patients were hypercalcemic, four with high serum PTH levels (high turnover bone disease, group 1) and four with low serum PTH levels (low turnover bone disease, group 2). In both groups, a decrease in serum Ca2+ and an increase in serum PTH was observed within the third month. In group 2, PTH levels reached the normal range. Because serum Ca2+ levels decreased to normal in both groups, it was possible to administer oral CaCO3 (10.5 +/- 2 g/day) to control serum PO4 and to stop Al gels. This did not induce any increase in serum Ca2+, whereas serum Al fell significantly. In group 1, to prevent a further rise in PTH, patients were treated with intravenous calcitriol (5 +/- 2 micrograms/week). This induced a reduction in the serum PTH without increasing serum Ca2+ or PO4. Within 12 months, an improvement in bone morphology was seen in both groups. It is concluded that the use of low Ca2+ dialysate corrects hypercalcemia in patients with PFD treated with high oral doses of CaCO3, and improves low turnover bone disease. The combination of low Ca2+ dialysate and intravenous calcitriol also improves high turnover bone disease.     

Effect of recombinant human erythropoietin on platelet production in dialysis patients

Two hundred forty-four anemic hemodialysis patients were randomized into recombinant erythropoietin and placebo-treated groups during a 12-wk double-blind phase, followed by a 24-wk open-label period. Mean platelet count rose from the baseline value of 242 x 10(9)/L to 264 x 10(9)/L on day 5 of epoetin therapy (P < 0.001, paired t test). Mean platelet count peaked at 290 x 10(9)/L on day 40 and remained at a significantly elevated level below the peak thereafter. The peak platelet count did not exceed the normal range in a majority of cases. Platelet count was unaffected by placebo. Patients without an erythropoietic response during the first few weeks of therapy exhibited a rise in platelet count comparable to that in patients with a satisfactory erythropoiesis. Patients with low initial serum ferritin concentrations had baseline platelet counts comparable to those with normal or high ferritin values and showed a similar rise in platelet count during therapy. As a group, patients with baseline platelet counts above 400 x 10(9)/L showed no rise in platelet count, whereas those with normal or reduced platelet counts showed a marked thrombopoietic response to epoetin. Erythropoietin therapy did not significantly alter the incidence of blood access thrombosis when compared with placebo treatment.     

Transfusion and recombinant human erythropoietin requirements differ between dialysis modalities

BACKGROUND: Before the routine use of recombinant human erythropoietin (rHuEpo), patients dialysed by peritoneal dialysis (PD) received fewer blood transfusions than patients on haemodialysis (HD). We compared transfusion practices in these groups now that the use of rHuEpo has become standard, while controlling for variables known to influence anaemia of end-stage renal disease (ESRD). Maintenance rHuEpo doses were also compared. METHODS: Data were examined for 157 HD and 126 PD patients during a 2-year period. Potential confounders included age, gender, albumin, iron deficiency, parathyroid hormone (PTH), underlying renal disease, comorbid illness, renal transplant, dialysis adequacy and duration. An intent-to-treat analysis was used, with sensitivity analyses to account for change in treatment and transplant. RESULTS: Mean haemoglobin (Hb) was not different (10.47 g/dl for HD, 10.71 g/dl for PD; P = 0.45). Mean monthly transfusion rate was higher for HD (0.47 units per month vs 0.19; P < 0.01). More HD patients received at least one transfusion (52.9 vs 40.9%; P < 0.01). The maintenance rHuEpo dose was higher for HD (7370 U/week vs 5790 U/week; P = 0.01). The only factors associated with risk of being transfused were dialysis duration and mode of dialysis (less risk for PD, odds-ratio 0.57; 95% confidence interval 0.35-0.92). CONCLUSIONS: Despite the routine use of rHuEpo, HD patients received more blood and rHuEpo than PD patients to achieve the same Hb. No patient factors were identified to account for this difference. The use of fewer transfusions and less rHuEpo in PD represents an advantage over HD in terms of both cost and safety.     

Hemocompatibility in hemodialysis and erythropoietin therapy

Two studies designed to investigate the effect of recombinant human erythropoietin (rHuEPO) treatment of anemia in chronic dialysis patients on hemocompatibility were conducted. Study 1, whose main aim was to establish whether treatment with rHuEPO enhances coagulation activation during dialysis, included 15 patients before rHuEPO therapy at a mean hematocrit (HCT) of 22.3% and then during therapy at a HCT of 29.3%. The plasma concentrations of the thrombin-antithrombin III complex were not higher during rHuEPO therapy than before it when performing hemodialysis with a Cuprophan membrane. No significant difference was demonstrated either in the values of activated clotting times (Hemochron), thrombocyte or white blood cell counts (Coulter S+II), or in plasma C5a concentrations (ELISA) established during dialysis sessions before and during rHuEPO therapy. In Study 2, which focused primarily on the question of whether or not rHuEPO therapy increases thrombocyte activation during hemodialysis, 8 patients on chronic dialysis were examined both before therapy at a mean HCT value of 22.1% and during rHuEPO therapy at a HCT of 31.5%, invariably during dialysis with either a Cuprophan or polyacrylonitrile (AN69HF) membrane. The plasma concentrations of beta-thromboglobulin (ELISA) did not differ between the examinations made during rHuEPO and before rHuEPO therapy; however, statistically significant differences were found between dialysis sessions involving Cuprophan and AN69HF membranes. No significant difference between examination before and during rHuEPO was demonstrated in activated clotting time nor thrombocyte and white blood cell counts in this study either. The authors conclude that rHuEPO therapy does not enhance coagulation activation during hemodialysis, does not have an effect on thrombocyte activation, and does not influence complement activation and changes in white blood cell counts.     

Effect of human recombinant erythropoietin therapy on panel reactive antibodies in chronic dialysis patients

To examine whether recombinant human erythropoietin (rhEPO) therapy results in decreased presensitization to foreign HLA antigens, we retrospectively analyzed data from 64 of 200 patients treated in a university hospital dialysis center between 1985 and 1995 who had undergone routine panel reactive antibody (PRA%) screening. Though a significant decrease in the annual frequency of highly sensitized patients over the years was noted, 16 patients followed for 27.1 +/- 3.7 months after initiation of rhEPO therapy until transplantation or blood transfusion showed no significant overall decrease in PRA%. Six highly presensitized patients had moderate but significant overall decrease in PRA%. However, in three of these patients the PRA% was unchanged and in the other three patients the PRA% remained over 50%. Thus rhEPO therapy reduced the incidence of highly presensitized patients, but previously presensitized patients remained presensitized. We conclude that removal of transfusional stimulation of lymphocytotoxic antibody production does not appear to benefit previously presensitized patients, possibly due to the maintenance of B-lymphocyte clonal expansion by unknown factors, or even by rhEPO itself.     

The effect of recombinant human erythropoietin on cardiovascular responses to postural stress in dialysis patients

The normal response to 45 degrees head-up tilt (decreased stroke volume and cardiac output and increased heart rate and peripheral resistance) is not seen in the majority of haemodialysis patients. This is due to both an abnormal baroreceptor reflex and increased venous tone which may be explained by a number of factors including hypoxia, acidosis and sodium retention. We have studied this response by impedance cardiography in eight chronic haemodialysis patients, both before and after 3 months of treatment with human recombinant erythropoietin. Before treatment the cardiovascular parameters were abnormal both at rest and on tilting in each patient. The change in each measurement following tilting was: stroke volume, 0.5 +/- 6%; cardiac output, 6 +/- 5%; peripheral resistance, -8 +/- 4%; and heart rate, 10 +/- 4%. After 3 months of erythropoietin (150 U/kg/week intravenously) the mean haematocrit had risen from 19.5 +/- 3% to 32.9 +/- 4% and all patients felt physically fitter. Impedance showed no change in the supine-indices but after tilting there was a dramatic fall in stroke volume (-26 +/- 7%) and cardiac output (-17 +/- 7%) and an increase in heart rate (15 +/- 4%) and peripheral resistance (28 +/- 10%) each moving towards the normal response. These results indicate that human recombinant erythropoietin normalizes the response to postural stress in these patients and suggest that anaemia is the principal cause of the abnormal venoconstriction seen in haemodialysis patients. The mechanisms involved warrant further investigation.     

Endogenous erythropoietin in patients on regular dialysis therapy

In a group of 66 patients with chronic renal failure having regular dialyzation treatment the serum concentration of endogenous erythropoietin (EPO), haemoglobin levels (Hb), haematocrit (Ht) and serum creatinine (Cr) were assessed. The examined subjects were never treated with recombinant erythropoietin and deficiency of iron, folic acid and vitamin B12 was ruled out. Endogenous EPO was assessed by the authors own RIA method, normal values being 24-42 mU/ml. The mean EPO concentration in the whole group of patients was 37.4 +/- 15.3 mU/ml, whereby 12 patients had an EPO serum concentration higher than the upper range of normal values. Between EPO concentrations and Hb values a certain positive correlation was found (r = 0.42). A similar relationship was revealed also between EPO concentrations and Ht values (r = 0.41). Patients with EPO values higher than 42 mU/ml had, as compared with the other patients, significantly higher values of erythrocytes (p .001). Statistical analysis did not reveal any relationship between EPO and Cr concentrations (r = -0.04). A low negative correlation was found between Cr and Hb values (r = -0.31) and between Cr and Ht values (r = -0.25). In the discussion the authors analyze the contemporary state of the problem of anaemia in chronic renal failure. Based on hitherto assembled knowledge they formulated the hypothesis ascribing considerable pathogenetic importance in the development of anemia to reduced sensitivity of bone marrow to EPO, probably as a result of retention of uraemic toxins and inhibitors of erythropoiesis. Inadequate EPO formation could be only a factor which makes it impossible for the developing anaemia to compensate and is due to an animpaired feedback at the level of recognition of the hypoxic signal.     

Recombinant human erythropoietin (rhEPO) treatment potentiates growth hormone (GH) response to growth hormone releasing hormone (GHRH) stimulation in hemodialysis patients

On the basis of previously described effects of recombinant human erythropoietin (rhEPO) treatment on endocrine abnormalities present in uremia, we assessed the possible effect of treatment with rhEPO on growth hormone (GH) response to growth hormone releasing hormone (GHRH) in a group of uremic patients. Eight patients on maintenance hemodialysis for 12 to 228 months, not previously treated with rhEPO, were tested with 100 micrograms of GHRH i.v. in bolus before and after three months of rhEPO treatment (40 U/kg i.v. three times a week). Before treatment, the GH response to GHRH was characterized, in uremic patients, by remarkable differences in plasma GH values and in the pattern of response curve in single patients. The variability of GH response was not modified after rhEPO treatment; however, an overall potentiation of GH response with a significant increase of plasma GH (p = 0.017 at 15 min, p = 0.035 at 30 min after GHRH injection) was observed in the tests performed after treatment. rhEPO administration induced an evident improvement of anemia, blood hemoglobin concentration being 5.3-7.6 g/dl before and 9.1-11.3 g/dl after treatment; however a demonstrable correlation between the potentiation of GH response to GHRH and the increase of hemoglobin concentration was not observed.     

Treatment with human recombinant erythropoietin and nutritional status of patients on lon term dialysis

In order to assess the effect of long term erythropoietin (EPO) therapy on the nutritional status of hemodialysed (HD) patients 2 groups of HD patients were studied: I-EPO treated for 72 +/- 8 mo, 12 patients, HD for 138 +/- 66 mo, II-control group, 14 patients with Ht 30%, HD for 121 +/- 35 mo. At the onset and after 6 years of follow up patients underwent the following examination: length, body weight, body mass index, body fat stores, arm muscle circumference and total serum protein, serum albumin, lymphocyte count, creatinine, urea, cholesterol and PTH. In EPO group mean BMI, body fat, arm muscle circumference, visceral protein and total lymphocyte count were not change. In control group the decrease in height, body weight, BMI, body fat stores, arm muscle circumference and albumin were observed. Elevation of PTH estimated in half of patients in EPO group and 75% of patients in control group could influence the nutritional status of hemodialysed patients. Conclusion: 1. Nutritional status of majority of hemodialysed patients was not change during six years EPO therapy. 2. Non EPO treated patients showed the decrease of anthropometric measurements and serum albumin.     

Recombinant erythropoietin and blood transfusions in cancer chemotherapy-induced anemia

BACKGROUND: We examined the relationship between religious attendance, religious affiliation, and use of acute hospital services by older medical patients. METHODS: Religious affiliation (n = 542) and church attendance (n = 455) were examined in a consecutive sample of medical patients aged 60 or older admitted to Duke University Medical Center. Information on use of acute hospital services during the year before admission and length of the current hospital stay was collected. Frequency of church attendance and religious affiliation were examined as predictors of hospital service use, controlling for age, sex, race, education, social support, depressive symptoms, physical functioning, and severity of medical illness as covariates using logistic regression. RESULTS: Patients who attended church weekly or more often were significantly less likely in the previous year to have been admitted to the hospital, had fewer hospital admissions, and spent fewer days in the hospital than those attending less often; these associations retained their significance after controlling for covariates. Patients unaffiliated with a religious community, while not using more acute hospital services in the year before admission, had significantly longer index hospital stays than those affiliated. Unaffiliated patients spent an average of 25 days in the hospital, compared with 11 days for affiliated patients; this association strengthened when physical health and other covariates were controlled. CONCLUSIONS: Participation in and affiliation with a religious community is associated with lower use of hospital services by medically ill older adults, a population of high users of health care services. Possible reasons for this association and its implications are discussed.     

Behavioral compliance with dialysis prescription in hemodialysis patients

The relationship between compliance and outcome is poorly understood, partially because there has been no gold standard for measuring compliance in hemodialysis patients. To investigate interrelationships between psychological, medical, and compliance factors, hemodialysis (HD) patients were studied with the Beck Depression Inventory, and a subset, the Cognitive Depression Index, the Perception of Illness Effects scale, and the Multidimensional Scale of Perceived Social Support. Behavioral compliance was measured in three ways: (1) percent time compliance (signifying "shortening behavior"); (2) percent attendance (signifying "skipping behavior) (3) percent total time compliance, assessing patients' time on dialysis normalized for prescribed time, including all shortenings and absences. Standard compliance indicators (predialysis serum potassium and phosphorus concentrations and interdialytic weight gain) were also analyzed. The patients' mean Beck Depression Inventory was in the range of mild depression. The prevalence of depression was 25.5%. Both depression indices correlated with Perception of Illness Effects scale scores. In general, social support was related to both measures of depression and perception of illness effects. Total time compliance was 95.8 +/- 5.0%. Younger patients were more likely to skip treatments compared with older patients. Time compliance comprised a wide spectrum, with most patients relatively compliant, whereas a small proportion received far less than their prescribed dialysis. Skipping and shortening behaviors did not correlate, suggesting that these constitute two separate types of noncompliant behaviors. Time compliance parameters did not correlate with potassium levels or interdialytic weight gain, but did correlate with phosphorus levels. Interrelationships between behavioral compliance measures and other parameters varied between units and patients of different gender. Finally, behavioral compliance patterns were stable over months in patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of recombinant human erythropoietin on synthesis of methylguanidine in uraemic patients on haemodialysis or continuous ambulatory peritoneal dialysis

The effect of recombinant human erythropoietin (rHuEPO) on synthesis of methylguanidine was studied in 6 uraemic patients on haemodialysis and 5 uraemic patients on continuous ambulatory peritoneal dialysis (CAPD). The two groups of patients were started on a 24-week course of thrice weekly 1500 IU of rHuEPO by the intravenous route. Serum methylguanidine level and methylguanidine/creatinine ratio were comparable in these groups. In the two groups no significant differences were observed in these measurements comparing the pretreatment values with those 4, 8, 12 or 24 weeks after starting rHuEPO administration. During rHuEPO therapy, serum methylguanidine levels and methylguanidine/creatinine ratio showed no considerable difference between the two groups. These findings suggest that administration of rHuEPO does not alter methylguanidine synthesis in uraemic patients on haemodialysis and CAPD.     

Pharmacokinetics of cefamandole in patients undergoing hemodialysis and peritoneal dialysis

The pharmacokinetics of cefamandole nafate, a new parenteral cephalosporin derivative, were evaluated in 11 patients with chronic renal failure (creatinine clearance less than 5 ml/min), including five patients during hemodialysis, four patients during routine peritoneal dialysis, and two patients during the interdialytic period. Peak serum levels of cefamandole were comparable to those observed in patients with normal renal function. Clearance of the drug during the interdialytic period and during hemodialysis and peritoneal dialysis was minimal, with a resultant significant prolongation of serum half-life. The nondialyzability of cefamandole is in contrast with reported studies of cephalothin, where significant reduction of the serum half-life was achieved during hemodialysis but not peritoneal dialysis. The concentration of cefamandole in the peritoneal dialysate after parenteral administration was observed to be bactericidal for many gram-negative pathogens and, with the exception of Streptococcus faecalis, most gram-positive organisms found in bacterial peritonitis in patients with severe renal failure. The present data suggest that if stable bactericidal serum levels of cefamandole are to be maintained during hemodialysis and peritoneal dialysis, a parenteral loading dose must be administered followed by one-half the loading dose every half-life.     

压滤式污泥过滤比阻测定方法

根据污泥机械脱水机理,建立了污泥比阻测试模型,设计了一种压滤式污泥比阻测试装置.结果表明:压滤法测得的污泥比阻Rp与布氏漏斗过滤实验测得的比阻Rv具有较好的一致性,两者线性相关系数R2=0.99,最大相对误差为8.0%,最小相对误差为1.0%,平均相对误差为5.0%;滤板开孔率的大小不会影响污泥比阻的测定,但当开孔率小于4.0%时,过滤介质和滤板的阻抗Rm(ε)随滤板开孔率的增加而减小,开孔率大于4.0%时,Rm(ε)与开孔率无关.分析了布氏漏斗测定污泥比阻时有效面积的影响;压滤式比阻测定仪测定污泥比阻时,实验压力的选取以获得适宜的过滤速度为宜,压力的改变对实验结果的影响较小;采用正压法,实验压力很容易维持恒定,通过测定活塞位移随时间的变化测定污泥的比阻,测量精度高,还可直观地反映污泥脱水速度的快慢.     

Tissue distribution of erythropoietin and erythropoietin receptor in the developing human fetus

The purpose of this exploratory study was to describe a group of African American women who smoke crack. Using aggregate data from 208 interviews with women crack smokers, we randomly selected 25 women's interview data to create the 25 life-lines. These life-lines were developed in a similar manner to the time-line analysis described by Fullilove and her colleagues (1992); we focused on events that are either extraordinarily disturbing (e.g., rape, incest, death of a child, etc.), events that are usual but often stressful (e.g., birth of a child, death of a parent, etc.), and on periods of drug use. We chose this method of analysis so as to highlight the context in which many women come to use crack cocaine. The life-lines provided a retrospective (but time-ordered) perspective and in several ways provided preliminary support for a stress-diathesis perspective.