Intravenous Iron Gluconate Administration Increases Circulating PAPP-A in Hemodialysis Patients

Background. Pregnancy-associated plasma protein-A (PAPP-A) is a proatherosclerotic molecule, interrelated with oxidative stress in hemodialysis (HD) patients. As intravenous (IV) iron might enhance oxidative stress in HD patients, this study investigates circulating PAPP-A during HD session and after IV iron administration. Methods. In 20 HD patients, plasma PAPP-A concentration was assessed immunochemically during 2 HD sessions (prior to HD and at 60, 130, and 240 min of HD session). Sodium ferric gluconate (62.5 mg) was given IV to all patients 65 min after the start of the second HD. Results. Sixty-five min after IV iron application, there was a significant increase in plasma PAPP-A (from 36.0 ± 9.9 to 79.6 ± 28.9 mU/L, p < 0.0001). At the end of this HD session, PAPP-A decreased significantly (p < 0.0001), but still remained 1.5-fold greater compared with predialysis levels (p < 0.0005). Conclusion. IV iron increases circulating PAPP-A, and in this way, it might contribute to more pronounced cardiovascular complications in HD patients.     

Reducing Sodium Intake in Hemodialysis Patients

A low salt diet is beneficial for the whole population but has particular advantages for hemodialyis patients because of the role of salt restriction in the management of hypertension and interdialytic weight gain (IDWG). Education on dietary salt intake based on general healthy eating guidelines, such as the "DASH-sodium" diet, should be provided for staff, families, and carers as well as patients. Anuric hemodialysis patients will need to take in approximately 1 l of water for every 8 g salt consumed. Patients who restrict salt intake to <6 g/day, and drink only when thirsty, should gain no more than 0.8 kg/day. Those with significantly greater weight gains, but predialysis serum sodium close to or higher than the dialysate sodium, need further review of their salt intake. Attempts to restrict fluid intake in these patients will be futile. Patients with high interdialytic weight gain (IDWG) and low predialysis sodium should be assessed for other reasons for fluid intake, such as high blood glucose or social drinking. For patients with poor tolerance of fluid removal during dialysis, and those who are hypertensive in the absence of fluid overload, a salt intake 5 g/day or less may be required. Dietary advice for these patients should be customized to ensure that they do not become malnourished.     

Iron and Infection in Hemodialysis Patients

Intravenous iron is an important component of the treatment of anemia of end‐stage renal disease (ESRD), but it is biologically plausible that iron could increase the risk of infection through impairment of neutrophil and T‐cell function and promotion of microbial growth. Any such increase in risk would be particularly important because infection is a significant cause of mortality and morbidity in dialysis patients. The overall evidence favors an association between iron and infection in hemodialysis patients, but the optimal iron management strategy to minimize infection risk has yet to be identified. There is a need for further research on this topic, particularly in light of increased utilization of intravenous iron following implementation of the bundled ESRD reimbursement system.     

Oral Glucose Tolerance Test After High-Dose i.v. Biotin Administration in Normoglucemic Hemodialysis Patients

Abnormal glucose metabolism in uremia may result from a complex interplay between decreased insulin secretion and insulin resistance. Recent studies report beneficial effect of biotin administration in glucose metabolism in diabetic animals and in a small number of patients with diabetes mellitus. The aim of the present study was to evaluate the response of oral glucose tolerance test (OGTT) to the i.v. administration of large doses of biotin in hemodialysis patients. Eleven hemodialysis patients aged 56.90 ± 11.20 (32–76) years on regular hemodialysis thrice a week for 2.72 ± 1.79 (1–7) years were studied. Fasting venous plasma glucose, glucosylated hemoglobin (%GH), and plasma glucose concentration 2 h after the administration of a 75-g glucose load were measured before, and 2 weeks and 2 months after administration of 50 mg of biotin i.v. postdialysis, and after a 2-month washout period. During the study, dialysis schedule and patients' medication, diet, and dry weight were kept unchanged. OGTT was abnormal in 4 patients before biotin administration and became normal in 3 patients (75%). Our results offer support to the findings of other studies about the beneficial effect of biotin in experimental or clinical diabetes mellitus, and argue for the involvement of biotin in glucose metabolism.     

Ferric Citrate Controls Phosphorus and Delivers Iron in Patients on Dialysis

Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of −2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.     

The Role of Hepcidin in Iron Homeostasis and Anemia in Hemodialysis Patients

Anemia is a common complication in hemodialysis (HD) patients. Despite the great success of recombinant human erythropoietin in clinical practice, resistance to this therapy is common. Additionally, nephrologists frequently witness a rapid and significant drop in their patients' hematocrit during the course of various acute events that regularly take place in this sensitive population. Hepcidin, a recently identified peptide, may mediate this development in many instances. Hepcidin production is regulated by hypoxia/anemia, iron status, and importantly, inflammation. This peptide can block iron absorption by the duodenum, iron release from both the liver (the main iron storage pool) and, more significantly, the macrophages interrupting iron recycling between senescent red cells and the reticuloendothelial system. The decreased availability of iron for erythropoiesis leads to the anemia of chronic disease or, in HD patients, aggravate an already existing anemia HD is now widely considered an inflammatory state probably accounting for the increased serum hepcidin levels that have been associated with it. The physiology of hepcidin and its possible contribution to the pathogenesis of anemia in HD patients are the subject of this review.     

Infection Risk with Bolus versus Maintenance Iron Supplementation in Hemodialysis Patients

Intravenous iron may promote bacterial growth and impair host defense, but the risk of infection associated with iron supplementation is not well defined. We conducted a retrospective cohort study of hemodialysis patients to compare the safety of bolus dosing, which provides a large amount of iron over a short period of time on an as-needed basis, with maintenance dosing, which provides smaller amounts of iron on a regular schedule to maintain iron repletion. Using clinical data from 117,050 patients of a large US dialysis provider merged with data from Medicare’s ESRD program, we estimated the effects of iron dosing patterns during repeated 1-month exposure periods on risks of mortality and infection-related hospitalizations during the subsequent 3 months. Of 776,203 exposure/follow-up pairs, 13% involved bolus dosing, 49% involved maintenance dosing, and 38% did not include exposure to iron. Multivariable additive risk models found that patients receiving bolus versus maintenance iron were at increased risk of infection-related hospitalization (risk difference [RD], 25 additional events/1000 patient-years; 95% confidence interval [CI], 16 to 33) during follow-up. Risks were largest among patients with a catheter (RD, 73 events/1000 patient-years; 95% CI, 48 to 99) and a recent infection (RD, 57 events/1000 patient-years; 95% CI, 19 to 99). We also observed an association between bolus dosing and infection-related mortality. Compared with no iron, maintenance dosing did not associate with increased risks for adverse outcomes. These results suggest that maintenance iron supplementation may result in fewer infections than bolus dosing, particularly among patients with a catheter.Anemia is common among patients with ESRD and associated with increased morbidity, mortality, and risk of hospitalization.¹ The anemia of ESRD is managed primarily with erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron supplements.² Recent safety concerns about ESAs^3,4 as well as changes in reimbursement policies in Medicare’s ESRD program have led to increased reliance on IV iron for the management of anemia.^5,6 The trend to greater use of iron is reinforced by evidence suggesting that more frequent iron use decreases ESA requirements in patients with treatment-refractory anemia.⁷Despite the prevalence of anemia in ESRD and potential risks associated with ESAs, considerable uncertainty exists about the optimal use of ESAs and IV iron in this population.^8,9 Iron treatment strategies have been reported to vary substantially among clinicians.^8,10 Some physicians administer large repletion doses of iron (hereafter termed bolus dosing) over consecutive dialysis sessions on an intermittent, as-needed basis.⁸ Others physicians instead provide low-dose administrations of iron (hereafter termed maintenance dosing) every 1–2 weeks to maintain iron stores. Currently, there is little evidence regarding the safety and effectiveness of these different approaches to iron supplementation.Infection risk has been a persistent concern associated with IV iron use in hemodialysis patients.^11–15 Frequent administration of iron may lead to oversaturation of transferrin and the release of free, catalytically active iron into circulation.¹⁶ Because iron is essential for bacterial growth, free iron may plausibly cause infection or worsen an existing infection.^17,18 Iron is also believed to impair host immune response by decreasing function of polymorphonuclear leukocytes.¹⁹ However, despite these concerns, to date, there have been few large epidemiologic studies of the infection risk of IV iron use in ESRD.To help identify the safest approach to IV iron use, we conducted a large-scale, nonexperimental study comparing the short-term infection risks associated with different IV iron dosing practices in a contemporary cohort of patients undergoing chronic hemodialysis.     

Paired Analysis of Outcomes After Kidney Transplantation in Peritoneal and Hemodialysis Patients

Background

The impact of dialysis modality before kidney transplantation (hemodialysis or peritoneal dialysis) on outcomes is not clear. In this study we retrospectively analyzed the impact of dialysis modality on posttransplant follow-up.

Effects of Low Sodium Dialysate in Chronic Hemodialysis Patients: An Echocardiographic Study

Background. Chronic kidney disease (CKD) and hemodialysis (HD) patients who cannot restrict sodium consumption in their diets sometimes develop significant saline excess and hypertension between dialyses. This study assessed the effect of relatively low sodium dialysate dialysis on changes of echocardiography in hemodialysis patients. Methods and Results. Eighteen patients with end stage renal failure on chronic HD were studied (8 females, 10 males) with a mean age 48.3 ± 14.6 (24–70) years. The mean time on HD was 30.8 ± 14.0 (12–60) months. Patients with hematocrit levels under 24% were excluded from the study. In all patients, echocardiography was performed thrice weekly before and after eight-week HD treatment with low sodium dialysate hemodialysis by the same operator (135 mEq/L for patients with sodium levels less than 137, 137 for patients with sodium levels over 137). Left atrium (LA) and left ventricle (LV) volumes and ejection fractions were measured, specifically: LV systolic diameter (LVSD), LV diastolic diameter (LVDD), interventricular septum (IVS), tricuspid regurgitation (TR), mitral regurgitation (MR), pulmonary artery pressure (PAP), and inferior vein cava diameter (IVCD). Results. In terms of echocardiographic parameters, LVSD, TR, PAP, and IVCD were statistically decreased after low-sodium dialysate treatments (p?=?0.002, 0.04, 0.013, and 0.00, respectively). Predialysis systolic and diastolic blood pressure (BP), post-dialysis systolic blood pressure, and interdialytic weight gain was statistically decreased when compared to basal levels (p?=?0.00, p?=?0.011, p?=?0.022, p?=?0.001, respectively). Conclusion A reduction of the dialysate sodium concentration based on the predialysis sodium levels of the patients could reduce the systolic BP and decrease the volume load on the heart as assessed by echocardiography. Within this short period, postdialysis diastolic BP could not be lowered. The effect of this approach should be studied in broad and lengthy series.     

可调钠透析防治高危血液透析患者低血压研究

目的：观察可调钠透析（PHD）在高危人群（高龄、糖尿病肾病及心功能不稳定）血液透析中防治低血压的作用。方法：选择30例维持性血液透析中的高危患者透析，治疗分两阶段进行，第1月行普通透析（CHD）为A组，透析液钠浓度138mmol／L，第2月行可调钠透析（PHD）为B组，透析液钠离子浓度由148mmol／L，线性下降到135mmol／L，透析时间均4．5h，患者自身交叉对照，两者血流速相等，脱水量恒定，透析过程中监测透析前后血清钠浓度，监测透析过程中低血压发生率。结果：CHD组与PHI）组相比，透析前后血清钠浓度无明显差异（P〉0．05）。CHD组与PHD组相比，PHD组低血压发生率较CHD组明显降低（p〈0．01）。与CHD相比，PHD的作用以不增加患者的钠负荷为代价，不造成透析间期体重增长过多。结论：PHD组可明显减少维持血液透析中高危人群的低血压的发生率。     

番茄红素对血液透析患者静脉铁剂诱导细胞因子的影响

目的：观察维持性血液透析（MHD）患者由静脉铁剂诱导的细胞因子,探讨番茄红素对其的干预作用。方法：60例MHD患者,随机分为两组（对照组和试验组,各30例）。对照组：在患者透析时给予蔗糖铁注射液100mg,2次/周,共10次,观察时间8周。试验组：除蔗糖铁注射液使用外,同时口服番茄红素胶囊,2粒/次,2次/d,用药8周,观察时间8周。观察并比较两组患者治疗前及治疗8周后的白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、白细胞介素-18（IL-18）、肿瘤坏死因子（TNF-α）等细胞因子指标的变化。结果：两组患者治疗后IL-1β、IL-6、IL-8、TNF-α、IL-18水平较治疗前均有显著性升高（P〈0.01或〈0.05）;但是试验组升高幅度显著性小于对照组（P〈0.01）。试验组患者治疗后IL-10水平较治疗前有显著性升高（P〈0.01）;并且试验组升高幅度显著性大于对照组（P〈0.05）。治疗后两组血清IL-1β、IL-6、IL-8、TNF-α、IL-18水平均与铁蛋白（SF）呈正相关（P〈0.01）。结论：静脉铁剂治疗加剧了MHD患者免疫细胞因子的调节;番茄红素可减少细胞因子过度调节而起到抗炎症作用。     

番茄红素对血液透析患者静脉铁剂诱导微炎症状态的影响

目的：观察维持性血液透析（MHD）患者由静脉铁剂诱导的微炎症状态,探讨番茄红素对其的干预作用。方法：60例MHD患者,随机分为对照组和试验组,每组各30例。对照组：在患者透析时给予蔗糖铁注射液100mg,2次／周,共10次,观察时间8周。试验组：除蔗糖铁注射液使用外,同时口服番茄红素胶囊,2粒／次,2次／d,用药8周,观察时间8周。观察并比较两组患者治疗前及治疗8周后的血红蛋白（Hb）、红细胞比容（Hct）、血清铁（SI）、铁蛋白（SF）、转铁蛋白饱和度（TSAT）以及白细胞介素-1β（IL-18）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、肿瘤坏死因子（TNF—α）、C反应蛋白（CRP）等指标的变化。结果：两组患者治疗后IL-18、IL-6、TNF—α及CRP水平较治疗前均有显著性升高（P〈0．01或P〈0．05）,但是试验组升高幅度显著性小于对照组（P〈0．01）;试验组患者治疗后IL-10水平较治疗前有显著性升高（P〈0．01）,并且试验组升高幅度显著性大于对照组（P〈0．05）;两组血清IL-6、TNF—α水平均与SF呈正相关（P〈0．01）：两组Hb、Hct、SI、SF、TSAT较治疗前均有显著性升高（P〈0．01）,并且两组升高幅度相似,差异无统计学意义。结论：静脉铁剂治疗加剧了MHD患者的微炎症状态。番茄红素可减轻这种微炎症状态。     

红细胞生成素治疗血液透析贫血患者给药途径的临床研究

人基因重组红细胞生成素治疗肾性贫血疗效显著，在临床有不同的给药途径。为探讨ｒＨｕＥ－ｐｏ治疗血液透析贫血患者的给药途径，随机将３５分皮下注射组和静脉注射组，结果显示，所有患者贫血均有明显缓解，两组患者的Ｈｂ，ＲＢＣ，Ｈｃｔ均明显上升，两组比较无显著性差异，而皮下组维持剂量低于静脉组，节约药量且操作方便，可减少不良反应。