不同频率血液透析滤过对维持性血液透析患者促红细胞生成素疗效的影响

目的:探讨不同频率血液透析滤过(hemodiafiltration,HDF)对维持性血液透析(maintenance hemodialysis,MHD)患者促红细胞生成素(erythropoietin,EPO)疗效的影响。方法:回顾性研究2017年06月~2019年06月杭州市中医院肾内科留治的MHD患者151例,按照在常规血液透析(hemodialysis,HD)基础上增加不同频率的HDF治疗分为HD组34例(常规HD治疗,不进行HDF治疗)、HDF1组25例(每月1次HDF)、HDF2组47例(每月2次HDF)、HDF4组45例(每月4次HDF)。所有入组患者每4周复查一次血红蛋白,根据血红蛋白水平调整EPO用量,分别于治疗前和治疗24周后测定血红蛋白、红细胞压积、超敏C反应蛋白、血清尿素氮、甲状旁腺素、干体重等指标。结果:治疗24周后,各组患者较入组时血红蛋白水平均明显上升(P均<0.05);HDF1组患者较入组时红细胞压积水平上升(P均<0.05);HDF1、HDF2、HDF4组患者较入组时ERI值、甲状旁腺素水平、超敏C反应蛋白水平下降(P均<0.05)。相关性分析显示,ERI值与铁蛋白、KT/V呈负相关关系,与甲状旁腺素、超敏C反应蛋白呈正相关关系。结论:不同频率的HDF治疗均能提高患者EPO的疗效,但提高HDF治疗的频率不能明显改善EPO疗效,就有效纠正MHD患者肾性贫血而言,可在常规HD基础上联合每月1次HDF治疗。     

Elderly Patients on Chronic Hemodialysis with Hyperparathyroidism: Increase of Hemoglobin Level after Intravenous Calcitriol

In patients on chronic hemodialysis (CHD), hyperparathyroidism (HPTH) is associated with anemia and resistance to erythropoietin (EPO). In the last few years, calcitriol intravenously (IV) has been used with success in the treatment of the HPTH, secondary to chronic renal failure. However, the effects of calcitriol on the hematological parameters of these patients have never been well evaluated. This study included 11 elderly CHD patients (f = 6, m = 5; mean age = 73.6 years, mean time on CHD = 42.8 months) with HPTH under EPO therapy (IV). They were treated for 12 months with calcitriol IV (mean dose=2.33 mcg/pt/week). Patients with iron deficiency anemia (ferritin < 200 ng/ml) were excluded. The patients were compared before and after 12 months of calcitriol treatment, with respect to several laboratory parameters and with respect to EPO dose. A paired t-test was used. After treatment, we found a decrease of PTH (634 vs. 418 pg/ml, P = 0.029); the serum calcium increased (8.8 vs. 9.9 mg/dl, P = 0.002); no differences were noted in the plasma levels of alkaline phosphatase, phosphorous, BUN, creatinine, Na and K. Mean levels of Hb (10.2 vs. 11.4 g/dl, P = 0.004) and the Hct (30 vs. 34.3, P = 0.004) increased after 12 months of calcitriol; the levels of serum iron (70 vs. 78 μg/dl, P = ns) and ferritin (531 vs. 785 ng/ml, P = ns) and the EPO dose (105 vs. 100 U/kg/week, P = ns) were similar before and after treatment. Our data show that the treatment of HPTH in CHD elderly patients with calcitriol can increase Hb level without increasing EPO dose.     

超纯透析液对血液透析患者促红素低反应性的影响

目的 探讨超纯透析液对维持性血液透析患者促红细胞生成素低反应性的影响.方法 选择维持性血液透析患者70例,随机分为普通透析液组(CD组,35例)和超纯透析液组(UPD组,35例),随访1年后观察两组超敏C反应蛋白(hs-CRP)和促红细胞生成素抵抗指数(Erythropoietin resistance index,ERI)的差异.结果 ①以ERI为因变量进行多元逐步线性回归分析,显示hs-CRP是ERI最为重要的独立影响因素(R2=0.699,p＜0.001);②随访1年后两组间hs-CRP差异有统计学意义(5.12±2.74 vs 3.77±2.19,P＜0.05),超纯透析液组ERI有明显改善(11.06±5.27 vs 16.42±7.05,p＜0.01).结论 ①C-反应蛋白升高是促红细胞生成素抵抗的独立影响因素;②使用超纯透析液可改善患者炎症状态和促红素低反应性.     

21例尿毒症患者甲状旁腺全切加前臂移植对改善透析患者肾性贫血的临床观察

目的探讨甲状旁腺全切除加部分前臂自体移植术（parathyroidectomy＋forearyauto—transplantation,PTX＋FAT）纠正重度继发性甲状旁腺功能亢进（secondaryhyperparathyroidism,SHPT）对维持性透析（maintenancehemodialysis,MHD）患者并发难治性肾性贫血的影响。方法选择MHD并发重度SHPT及难治性肾性贫血患者21例,均为经规范的药物治疗无效者行PTX＋FAT治疗,观察术前、术后第3、6、12个月时患者的血清全段甲状旁腺素（intactparathyroidhormone,i盯H）、钙（Ca）、磷（P）、血红蛋白（Hb）、红细胞压积（Hct）、血清铁蛋白（SF）、转铁蛋白饱和度（TSAT）、血清白蛋白（Alb）、KT／V等指标变化,同时记录患者的促红细胞生成素（recombinanthu—manerythropoietin,rHuEPO）用量。结果所有患者与术前相比血清iPTH、Ca、P迅速下降,从术后第3个月开始贫血得到逐步改善,术后第12个月Hb和Hct较术前显著升高（P〈0．05）,术后第6个月rHuEPO用量减少,与术前相比差异显著（P〈0．01）,术后第12个月rHuEPO用量大幅减少,与术前相比有显著性差异（P〈O．01）。手术前、后SF、TSAT、Alb、KT／V等指标差异无统计学意义（P〉0．05）。结论重度SHPT维持性血液透析患者在PTX＋FAT术后可迅速降低iPTH水平并显著改善MHD患者的难治性肾性贫血,减少rHuEPO用量,提示重度SHPT是影响肾性贫血的一个重要因素,其作用可能部分与rHuEPO抵抗有关。     

Elderly patients on chronic hemodialysis: Effect of the secondary hyperparathyroidism on the hemoglobin level

In patients on chronic hemodialysis (CHD)hyperparathyroidism (HPTH) is associated withanemia and resistance to erythropoietin (EPO). This study included 86 CHD elderly pts (meanage 74.8 y, mean time on CHD = 50.5 mos); theywere divided into two groups: I (n = 31) – PTH> 250 pg/mL and II (n = 55) – PTH < 250 pg/mL.All these patients had been on CHD for> 6 mos. No differences were found betweengroups in respect to age, sex distribution andtime on CHD. The levels of creatinine, BUN, Ca,Al, Fe, albumin and ferritin were similar.Group I had a higher P level (5.4 vs 4.3 mg/dL,p = 0.001) and Ca x P (53.5 vs 43.7, p =0.009). Also the Hct (31 vs 33.5%, p = 0.008)and the Hb (10.4 vs 11.2 g/dL, p = 0.009) values werelower in Group I. The EPO dose (88 vs 85 U/kg/week,p = ns) was similar in the two groups.Our data showed that elderly patients with HPTHhave lower Hct and Hb levels than do youngerpatients on a similar EPO dose. We believethese patients will need a more aggressivetherapy with calcitriol.     

Treatment with Calcimimetic (Cinacalcet) Alters Epoetin Dosage Requirements in Dialysis Patients: Preliminary Report

Abstract

Background: Secondary hyperparathyroidism (SHPT), known complication of chronic renal failure, in addition to effects on bone and cardiovascular systems, is associated with reduced response to erythropoietin (EPO). Calcimimetics such as cinacalcet are the latest generation of drugs used in the treatment of SHPT. Few studies have evaluated the effect of cinacalcet on anemia associated with SHPT in dialysis patients, while no study has compared this cinacalcet effect with that of vitamin D analogs such as paricalcitol. Patients and methods: Using a retrospective chart-based review of dialysis patients’ records to identify patients being treated with either cinacalcet or paricalcitol alone, matched for the same EPO treatment, which had been followed for 1 year, we have evaluated the effect of cinacalcet on anemia compared to that of paricalcitol. Results: Ten patient records were found that fit the criteria, five treated with cinacalcet (Group 1) and five treated with paricalcitol (Group 2), all treated with the same dose of darbepoetin. Darbepoetin dosage was the only parameter that significantly changed between groups, decreasing in Group 1 (?33%, p = 0.009) while remaining unchanged in Group 2. PTH-level reduction, which was significant versus baseline in both groups, although not statistically different between groups, was higher with cinacalcet. Conclusion: The combination of lower EPO dose in cinacalcet-treated patients compared with paricalcitol-treated patients, along with good SHPT control is a novel information and might have considerable benefits in dialysis patients not only preventing bone (fractures) and cardiovascular system (calcifications) damages but also in terms of cost savings via a reduction of EPO dosage.     

Effect of an intravenous iron dextran regimen on iron stores, hemoglobin, and erythropoietin requirements in hemodialysis patients

Iron deficiency is a common cause of delayed or diminished response to erythropoietin (EPO) in hemodialysis patients. Although oral iron is often prescribed to replete iron stores, this approach to iron supplementation may not be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an effective alternative approach to replete iron stores and may facilitate more cost-effective use of EPO. The purpose of this study was to evaluate an IV iron dextran regimen that consisted of a loading dose phase followed by monthly maintenance doses of iron dextran. The effect of this regimen on iron stores, hemoglobin, and EPO doses was evaluated. This was an open prospective study in adult hemodialysis patients who were iron deficient as defined by a serum ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%. Patients were loaded with 1 g iron dextran in five divided doses and then received monthly maintenance doses of 100 mg for the 4-month study period. Values of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month study period. Thirty hemodialysis patients receiving EPO were identified as being iron deficient and were enrolled in the study. The mean serum ferritin increased significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P = 0.002). Values for hemoglobin did not change significantly during the study period; however, there was a significant reduction in EPO dose from a mean baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P = 0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per year could be saved by use of IV iron dextran. The administration of the IV iron dextran regimen in the iron-deficient hemodialysis population was effective at repleting and maintaining iron stores and reducing EPO use.     

Effective treatment of secondary hyperparathyroidism in hemodialysis patients by titration of intravenous calcitriol dosage.

AIM: Effective treatment of secondary hyperparathyroidism (HPTH) with intravenous (i.v.) administration of calcitriol in hemodialysis patients. PATIENTS AND METHODS: The current study evaluates the use of i.v. calcitriol dosing in relation to the severity of the HPTH in 35 hemodialysis patients with serum phosphate < 6.5 mg/dl. Arbitrarily, patients with plasma IPTH levels (intact PTH) between 288 and 576 pg/ml (288 pg/ml = four-fold the upper normal limit) were given initially 1 microg i.v. calcitriol at the end of each dialysis (group A, n = 15). Patients with IPTH between 577 and 864 pg/ml received 2 microg i.v. calcitriol (group B, n = 10) and patients with IPTH more than 865 pg/ml were given 3 - 4 microg i.v. calcitriol (group C, n = 10). As IPTH levels decreased, the dose of i.v. calcitriol was also decreased gradually. Patients were followed-up for 4 months after the end of calcitriol treatment. RESULTS: During the i.v. calcitriol treatment period, the observed plasma IPTH concentrations compared with the baseline values were significantly lower (p < 0.01 for A and B group and p < 0.05 for C group) from the sixth month onwards in group A and C and from the third month onwards in group B. At the 12th month of follow-up, all patients being off i.v. calcitriol treatment for four months, a sharp and significant increase (p < 0.01 for group A and B and p < 0.05 for group C) of plasma IPTH was recorded in all three groups of patients. Alkaline phosphatase was also gradually decreased in all studied groups. Serum Ca and P remained unchanged in most patients. CONCLUSION: In conclusion, the study presented here demonstrates that the titration of i.v. calcitriol dosage according to the severity of HPTH is an effective and safe treatment of HPTH in chronic hemodialysis patients. It also shows that parathyroidectomy could be avoided in the majority of patients with severe HPTH, if an appropriate dose of calcitriol not aggravating hyperphosphatemia is administered.     

不同血液净化方式联合骨化三醇冲击治疗对维持性血液透析患者肾性骨病指标的影响及意义

目的 通过观察不同血液净化方式联合骨化三醇冲击治疗对维持性血液透析患者肾性骨病指标的影响,探讨肾性骨病合适的治疗方案.方法 将60例符合标准的患者按随机数字表法分为3组,每组20例.所有患者采用骨化三醇冲击治疗,使用低钙透析液.普通透析组患者采用常规透析,血液透析滤过组患者采用血液透析滤过治疗,每周透析3次,其中血液透析滤过治疗每周1次.血液透析灌流组患者采用血液透析联合血液灌流治疗,每周透析3次,其中血液透析联合血液灌流治疗每周1次.结果 3组患者使用不同透析方式联合药物治疗3个月后发现,治疗前3组患者血钙、血磷、血甲状旁腺激素水平比较差异无统计学意义(P＞0.05),治疗后1个月血液透析灌流组患者血磷与普通透析组患者比较差异有统计学意义(P＜0.05),而血液透析滤过组患者的血磷与普通透析组比较差异无统计学意义(P＞0.05);治疗后3个月血液透析滤过组和血液透析组患者的血甲状旁腺激素、血磷、血钙水平与普通透析组比较差异也有统计学意义(P＜0.05),而血液透析滤过组和血液透析灌流组间血甲状旁腺激素、血磷、血钙水平比较差异无统计学意义(P＞0.05).结论 对于维持性血液透析的患者存在高磷血症以及继发性甲状旁腺激素的升高等肾性骨病的指标异常,可以应用血液透析滤过以及血液透析联合血液灌流治疗,且安全可行.     

口服与静脉铁剂治疗肾性贫血的对比观察

目的观察口服与静脉铁剂在维持性血液透析患者肾性贫血治疗中的应用。方法选择48例合并肾性贫血的维持性血液透析患者为研究对象,随机分为2组,口服组22例,静脉组26例。2组血液透析方案和红细胞生成素用量相同,口服组口服多糖铁复合物300mg／d,静脉组采用静脉滴注低分子右旋糖酐铁100mg／周,观察时间为6个月。结果6个月后,静脉组总有效率高于口服组（P〈0．01）,血红蛋白和血细胞压积高于口服组（P〈0．05）,2组转铁蛋白饱和度、血清铁蛋白及C反应蛋白无显著差异（P〉0．05）,而整体费用支出无显著差异（P〉0．05）。结论对于肾性贫血患者的长期巩固治疗,静脉补铁较口服补铁效果更好,并发症少,且并不增加治疗费用。     

Reducing versus discontinuing erythropoietin at high hemoglobin levels

A 2006 change in Medicare policy allowed reimbursement for erythropoietin (EPO) in dialysis patients whose most recent hemoglobin exceeded 13 g/dl. We investigated the effects of a change in dosing algorithm implemented in response to this policy, in which EPO dosages were reduced instead of temporarily discontinued for hemoglobin levels > or =13 g/dl. Among 1688 individuals in 18 hemodialysis units, the reduction protocol resulted in more hemoglobin levels > or =13 g/dl (P < 0.0001), fewer levels between 11 and 12.9 g/dl (P < or = 0.004), no difference in the proportion of levels <11 g/dl, and more EPO administered per session (P < 0.0001) than the discontinuation protocol. In view of the expense of erythropoiesis stimulating agents and the uncertainty of the safety of using EPO to achieve high hemoglobin targets, this study suggests that discontinuation, rather than reduction, of EPO treatment is appropriate when hemoglobin reaches 13 g/dl in hemodialysis patients.     

Correction of deficient phagocytosis during erythropoietin treatment in maintenance hemodialysis patients.

Studies on the influence of erythropoietin (EPO) on granulocyte or monocyte function are scant. In this study, the effect of EPO on polymorphonuclear cell (PMN) respiratory burst activity was evaluated in a double-blind, placebo-controlled study in 22 patients on maintenance hemodialysis. As an index of phagocyte respiratory burst activity, the increase in 14CO2 production from labeled glucose-1-C, after challenge with latex and zymosan, was measured on predialysis whole blood samples, before and after EPO-treatment. As controls, 56 nonuremics and 49 non-EPO-treated hemodialysis patients were evaluated. Before EPO treatment 14CO2 production was depressed to 75.7% (latex) and 54.6% (zymosan) of healthy controls (P less than 0.01). A marked improvement was observed after a mean treatment period of 4 months (latex, 115 +/- 12 to 172 +/- 14; zymosan, 178 +/- 19 to 412 +/- 36 dpm/10(3) PMN, P less than 0.01). Placebo treatment induced no changes. The improvement became more pronounced with prolongation of treatment. A significant correlation between hematocrit and 14CO2 production was observed in the EPO treatment group (latex: n = 44, r = 0.47, P less than 0.05; zymosan: n = 44, r = 0.57, P less than 0.001). No correlation was found with serum ferritin. We conclude that the depressed phagocyte glycolytic activity of hemodialyzed uremics is normalized during correction of anemia by EPO. This may be attributed to factors other than a reduction in the body iron stores.     

非糖尿病血液透析患者的糖化血红蛋白的水平变化

目的观察血液透析患者的糖化血红蛋白（HbAlc）,并分析其相关的影响因素。方法选择非糖尿病血液透析患者54例（透析组）,检测HbAlc、血红蛋白（Hb）、透析时间（Ht）、红细胞生成素（EPO）剂量等;另设对照组为同期进行糖耐量试验（OGTT）证实为非糖尿病的一般查体人群121例。比较2组HbAlc,并应用多元线性回归分析透析组中Hb、每周Ht及EPO剂量对HbAlc的影响。结果透析组与对照组HbAlc分别是（5．3％±0．6％）和（5．8％±0．5％）,说明相对于非糖尿病的一般人群,非糖尿病血液透析患者的HbAlc水平显著低下。Hb、Ht、EPO对HbAlc均无明显的影响（P〉0．05）。结论非糖尿病血液透析患者HbAlc水平较正常人显著降低。     

Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study

Evenepoel P, Sprangers B, Lerut E, Bammens B, Claes K, Kuypers D, Meijers B, Vanrenterghem Y. Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01524.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: The calcimimetic cinacalcet is approved for treating secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. Biochemical profiles and clinical outcomes in patients discontinuing cinacalcet at the time of transplantation are scarce. Methods: We performed a prospective observational cohort study, including 303 incident renal transplant recipients, of whom 21 were on cinacalcet treatment at the time of transplantation. Parameters of mineral metabolism and incidence of parathyroidectomy and nephrocalcinosis in patients discontinuing cinacalcet at the time of transplantation patients (“cinacalcet +”) were compared to cinacalcet‐naïve patients (“cinacalcet –”). Mean follow‐up was 35.6 ± 15.8 months. Results: At the time of transplantation, parameters of mineral metabolism were similar in both groups. Conversely, at month 3, serum ionized calcium (p = 0.0007), calcitriol (p = 0.02), biointact parathyroid hormone (p = 0.06) levels and urinary fractional excretion of phosphorus (p = 0.06) were higher, while serum phosphorus levels (p = 0.06) were lower in “cinacalcet +.” Analysis based on matching at the time of initiation showed that the course of post‐transplant mineral metabolism in cinacalcet‐treated patients (median treatment period 12.5 months) vs. cinacalcet‐naïve patients was identical. “Cinacalcet +” patients are characterized by a high‐incidence proportion of both post‐transplant nephrocalcinosis (45% at month 3) and parathyroidectomy (28.6%). No difference in renal function was observed between “cinacalcet +” and “cinacalcet?” patients. Conclusion: Cinacalcet does not affect the course of secondary hyperparathyroidism in patients awaiting kidney transplantation. Biochemical profiles and a high parathyroidectomy rate suggest rebound hyperparathyroidism in renal transplant recipients discontinuing cinacalcet at the time of transplantation, which may be related to the short exposure time specific to this population. Risk/benefit studies are urgently required to define the role of continued calcimimetic treatment in renal transplant recipients and to determine the optimal treatment of secondary hyperparathyroidism in patients listed for transplantation.     

Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation

Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 ± 74 mo vs 57 ± 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)², and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation.     

Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.     

Soluble transferrin receptor is correlated with erythropoietin sensitivity in dialysis patients.

BACKGROUND: Iron deficiency is the most common cause of erythropoietin (EPO) resistance in dialyzed patients with renal anemia. Subclinical or functional iron deficiency is difficult to diagnose in these patients. The soluble transferrin receptor (sTf-R) is considered as a sensitive and specific indicator of bone marrow iron availability. PATIENTS AND METHODS: To evaluate the clinical usefulness of this novel marker, we investigated relationships between EPO requirements and various hematological and biochemical parameters of erythropoiesis in 27 pediatric end-stage renal failure patients treated by hemodialysis (HD, n = 11) or chronic peritoneal dialysis (PD, n = 16). Iron was substituted intravenously once or twice per week in HD, and by daily oral administration to PD patients. Serum sTf-R concentrations were measured by an enzyme-linked immunosorbent assay. Serum ferritin and transferrin concentrations were determined using nephelometric assays. Hemoglobin and iron levels were estimated by automated procedures. RESULTS: While neither transferrin saturation nor serum ferritin concentrations were indicative of EPO requirements, a highly significant correlation between the EPO efficacy index (EPO dose divided by hemoglobin concentration) and sTf-R was observed (r = 0.65, p = 0.001). The intravenous iron substitution in HD patients was associated with higher ferritin concentrations compared to the orally substituted PD patients (280+/-100 ng/ml vs. 124+/-83 ng/ml, p<0.002). In contrast, sTf-R concentrations were similar in both treatment groups (25.7+/-7.7 nM vs. 27+/-10.8 nM, n.s.), as were hemoglobin concentrations and EPO requirements. CONCLUSION: Our results suggest that sTf-R is a more sensitive indicator of functional iron deficiency and impaired EPO responsiveness than serum ferritin or transferrin saturation in dialyzed patients. Intensified iron substitution to patients with elevated sTf-R concentrations may considerably improve the cost efficacy of EPO treatment.     

Serum erythropoietin and erythropoiesis in primary and secondary hyperparathyroidism: effect of parathyroidectomy.

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.     

A controlled trial of the early treatment of secondary hyperparathyroidism with calcitriol in hemodialysis patients

BACKGROUND: Calcitriol is widely used in conjunction with phosphorus-binders containing calcium to treat secondary hyperparathyroidism in dialysis patients. Its efficacy in patients with severe hyperparathyroidism is diminished, in part, due to glandular hyperplasia associated with decreased calcitriol and calcium receptors. SUBJECTS AND METHODS: We, therefore, developed a prospective, randomized trial comparing i.v. calcitriol plus calcium carbonate (CaCO3) compared to CaCO3 alone (control) in patients with mild to moderate hyperparathyroidism who were within the first year of initiating hemodialysis. Patients underwent calcium (Ca) suppression/stimulation testing at baseline and after six and twelve months of treatment to indirectly assess parathyroid gland hyperplasia. RESULTS: In the calcitriol group, the amino-terminal parathyroid hormone (N-PTH) decreased significantly from a baseline value of 70 +/- 12 pg/ml at month zero to 22 +/- 7 and 19 +/- 6 pg/ml at months 6 and 12, respectively (the conversion factor of amino-terminal PTH to intact PTH is 6, i.e., 10 pg/ml N-PTH equals 60 pg/ml intact PTH). In contrast, the N-PTH levels in the CaCO3 alone group did not change. The change in nadir N-PTH levels at month 12 compared to month zero decreased by 14 +/- 7% in the calcitriol group but increased by 96 +/- 59% in the control group (p < 0.05). In addition, the increment in N-PTH levels during hypocalcemic stimulation decreased by 68 +/- 6% at month 12 compared to month zero but increased by 61 +/- 42% in the control group. Although total calcium and phosphorus levels were not different between the two groups, ionized calcium values were higher in the calcitriol group. The incidence of hypercalcemia was the same in both groups and the episodes were asymptomatic. CONCLUSION: Pulse calcitriol therapy is effective in preventing progression of secondary hyperparathyroidism in hemodialysis patients with mild to moderate disease. Based on Ca suppression/stimulation tests, calcitriol was more successful in preventing gland growth than CaCO3 alone. Further studies are needed to determine if the strategy of early treatment of mild to moderate hyperparathyroidism by pulse calcitriol is safe and effective in hemodialysis in patients.     

维持性血液透析患者睡眠质量和日间嗜睡状况的研究

目的 本研究调查维持性血透患者的睡眠质量和日间嗜睡状况,探讨影响睡眠质量的相关因素。 方法 112例维持性高通量血透患者和53例健康人对照进行匹兹堡睡眠质量指数（PSQI）问卷评估睡眠质量和Epworth Sleep Scale（ESS）问卷评估日间嗜睡程度,并比较结果。比较睡眠好（PSQI总分≤5）和睡眠差（PSQI总分>5）的患者PSQI 7部分得分及各种睡眠障碍的原因;观察不同时间段血透患者的睡眠情况;多元线性回归和logistic回归分析年龄、透析龄等临床基本资料以及血钙、磷、血红蛋白等生化指标与睡眠质量的相关性。 结果 血透患者PSQI总分高于对照组（7.02±4.94比3.28±2.79,P < 0.05）,而ESS总分低于对照组[3（0～6）比8（4.25～11.75）,P < 0.05]。58%的血透患者睡眠差,入睡时间明显延长（30 min比15 min,P < 0.05）,失眠是主要原因。早、中、夜班血透睡眠质量无显著差异。年龄（OR = 1.75,P = 0.003）、透析龄（OR = 1.26,P = 0.008）、血红蛋白（OR = 0.64,P = 0.008）、钙磷乘积（OR = 1.60,P = 0.02）与睡眠质量评分显著相关。 结论 血透患者普遍存在睡眠不良,老年、透析龄长、贫血、钙磷乘积升高是危险因素。