Effects of three kinds of erythropoiesis-stimulating agents on renal anemia in Japanese non-dialysis chronic kidney disease patients

Background

Erythropoiesis-stimulating agents (ESAs) are standard therapy for chronic kidney disease (CKD) patients with renal anemia. However, few studies have compared the effects of different ESAs on anemia in identical pre-dialysis CKD patients.

Methods

Seventy-nine patients who switched from epoetin beta to darbepoetin alfa (Group 1), and 82 patients who switched from darbepoetin alfa to epoetin beta pegol (Group 2) were enrolled in this study. Clinical and laboratory parameters were assessed for 6 months before and after switching ESAs. The prevalence of adverse events, the dose conversion ratio of ESAs, and the frequency of ESA administration were also analyzed.

Results

Analysis of variance showed that switching ESAs did not significantly change hemoglobin levels for the study duration in both groups (mean hemoglobin 10.3–10.5 g/dL in Group 1 and 10.4–10.7 g/dL in Group 2). Estimated glomerular filtration rate, blood pressure, transferrin saturation, ferritin, and albumin remained constant in both groups. The prevalence of adverse effects was quite low (0–3.8 %) during both 6-month study periods. The mean dose conversion ratio for epoetin beta:darbepoetin alfa was 163.7 units:1 μg and for darbepoetin alfa:epoetin beta pegol was 1.08 μg:1 μg. The intervals of ESA administration significantly differed (epoetin beta pegol > darbepoetin alfa > epoetin beta).

Conclusions

Epoetin beta, darbepoetin alfa, and epoetin beta pegol are effective and well-tolerated agents for managing anemia in Japanese pre-dialysis CKD patients. The intervals of ESA administration to maintain a patient’s target hemoglobin were longer in the order of epoetin beta pegol > darbepoetin alfa > epoetin beta.     

Body composition affects the response to erythropoiesis-stimulating agents in patients with chronic kidney disease in dialysis

Background: The response to erythropoiesis-stimulating agents (ESA) in patients with chronic kidney disease (CKD) is variable. The body mass index (BMI) variations can modify the response to ESA. The objective was to assess the effect of body composition on the response to ESA in dialysis patients. Methods: This is an observational cross-sectional study. Prevalent hemodialysis and peritoneal dialysis (PD) patients were selected. In the same day, a single blood test, a body composition analysis using bioimpedance spectroscopy and anthropometric measurements were performed. We collected ESA doses. We analyzed erythropoietin resistance index (ERI). The ERI was calculated dividing the weekly weight-adjusted (kg) dose of ESA (IU) by the hemoglobin level (g/dL). Results: The study was comprised of 218 patients (58% men; age 65 (16) years old; 80% hemodialysis, 20% PD). There was an inverse correlation between ERI and BMI (p?=?0.01), fat tissue index (FTI) (p?=?0.01) and prealbumin (p?=?0.04). We found an independent association between higher ERI levels and lower FTI and prealbumin values. Conclusion: Response to ESA is influenced by body composition. Fat tissue favors the body’s response to ESA.     

慢性肾脏疾病非透析患者高磷血症的管理

高磷血症是慢性肾脏病(chronic kidney disease,CKD)患者的重要并发症之一。血磷水平长期过高可导致甲状旁腺功能亢进、肾性骨营养不良、血管钙化等多种并发症,而且与病死率增加密切相关。控制血磷水平达标可有效改善CKD患者的预后。本文将结合最新研究成果进一步探讨高磷血症的发生机制、疾病危害,以及非透析高磷血症患者的临床监测路径和治疗方法,为临床工作提供参考。     

慢性肾脏病非透析患者心理状况的相关性研究

本研究对慢性肾脏病非透析患者的情绪、心理健康状况、人格等心理因素与病情的相关性进行研究。     

Antibody-mediated pure red cell aplasia in chronic kidney disease patients receiving erythropoiesis-stimulating agents: new insights

Antibody-mediated pure red cell aplasia is a very rare but devastating condition affecting patients receiving treatment with erythropoiesis-stimulating agents. New cases continue to emerge, generally in clusters, consistent with an 'environmental' trigger to its pathogenesis. Defining the causes of antibody-mediated pure red cell aplasia is clearly of importance for patients with chronic kidney disease, but any developments in this area may also have relevance to other disease areas as therapeutic delivery of endogenous proteins rapidly increases. This review focuses on the current knowledge regarding the etiology of antibody-mediated pure red cell aplasia and the current approach to therapy.     

Salt sensitivity of blood pressure in non-dialysis patients with chronic kidney disease

Background: Chronic kidney disease (CKD) is a world-wide public health problem. Hypertension is both a cause and a complication of CKD, and a risk factor for progression of kidney disease. The effect of salt intake on blood pressure (BP) and the salt sensitivity in non-dialysis patients with CKD were studied. Methods: One hundred and thirty non-dialysis patients with CKD were enrolled in the present study. Daily urinary excretion of sodium (representative of daily sodium intake) and BP was monitored in conditions of original eating habits. Estimated glomerular filtration rate (eGFR) was measured by the creatinine clearance (Ccr). Results: There was a linear positive relationship between the salt intake and systolic blood pressure (SBP) (β?=?0.250, p?=?0.004). It had been found that the log of BP/24-h urinary sodium (salt sensitivity index) had linear relationship with the log of eGFR (β_syst?=??0.364, p?=?0.000, β_diast?=??0.345, p?=?0.000, respectively). Multi-stepwise regression analysis showed SBP was mainly influenced by salt intake and eGFR. There was a negative correlation between diastolic blood pressure (DBP) and age. Conclusion: These results demonstrated a linear relationship between the salt intake and SBP in non-dialysis patients with CKD. The salt sensitivity of BP rose with the decline of renal function.     

Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease

Purpose

Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients.

Materials and methods

Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied.

Results

There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (β = ? 0.548, P < 0.001) and lower levels of 25(OH)D (β = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001).

Conclusions

Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

     

Erythropoietin-stimulating agents in chronic kidney disease: a response to hyporesponsiveness

Hyporesponsiveness to erythropoietin stimulating agents occurs frequently, and may be observed at initiation of treatment or during maintenance therapy. An inverse relationship between hyporesponsiveness and incident cardiovascular events has been reported. It is related at least in part to co-morbidity and its occurrence requires a search for the cause. Treatment of anemia in hyporesponsive patients should be individualized, with consideration given to the indication for ESA therapy, the target hemoglobin for therapy, and maximal dose limitations.     

Sagittal abdominal diameter and Framingham risk score in non-dialysis chronic kidney disease patients

Background

Chronic kidney disease (CKD) is very common now and is associated with high overall and cardiovascular mortality. Numerous studies have reported that abdominal obesity is a risk factor for cardiovascular mortality. We investigated the link between sagittal abdominal diameter (SAD) and Framingham risk score in non-dialysis CKD patients.

Methods

In a cross-sectional study, we enrolled 307 prevalent non-dialysis CKD patients (175 males, aged 50.7?±?17.04 years). SAD and Framingham risk score were measured.

Results

Framingham cardiovascular disease risk score was independently predicted by SAD (P?<?0.01), GFR (P?<?0.01) and diabetic history (P?<?0.05). Adjusted R² of the model was 0.178. SAD could be independently predicted by BMI (P?<?0.01), diabetic history (P?<?0.01), GFR (P?<?0.01) and age (P?<?0.01). Adjusted R² of the model was 0.409. Using receiver operating characteristic (ROC) curve, a cutoff SAD value of 16.55 cm was determined with sensitivity of 63.7%, specificity of 58.3%.

Conclusion

Elevated SAD is significantly associated with increased Framingham risk score in non-dialysis CKD patients. SAD can be predicted by patients’ BMI, diabetic history, renal function and age. Further investigation is needed to explore the potential benefits of central obesity lowering therapy in this patient group.

     

558例非透析慢性肾脏病患者骨代谢指标的分析

目的 调查我院非透析慢性肾脏病患者骨代谢指标,为早期监测慢性肾脏病的矿物质及骨代谢异常提供依据。方法 回顾性分析我科住院的非透析慢性肾脏病患者558例,检测血甲状旁腺素(iPTH) , β-胶原特殊序列测定(β-CTX )、骨钙素、25-羟基维生素D3[25(OH)D3]、钙、磷、碱性磷酸酶(AKP)、肌酐、白蛋白、血糖等指标,留取晨尿进行尿常规及24 h尿蛋白定量检查,并分析相关影响因素。结果558例CKD患者平均年龄(70.6±15. 6 )岁,其中男性51.1%,女性48.9%,骨代谢指标男女性别间差异无统计学意义(P > 0. 05)。iPTH , β-CTX、骨钙素、血磷在CKD1-3期患者间差异无统计学意义,但与CKD4、5期患者差异有统计学意义(P<0.001);AKP在CKD5期明显升高。25(OH)D3在CKD1-5期患者中差异无统计学意义,各期CKD患者均存在25(OH)D3的不足及缺乏,其患病率分别为24.7% ,70.1%。单因素相关分析显示,MDRD-eGFR与iPTH ( r=–0. 457 ) , β-CTX (r=–0. 501)、骨钙素(r=–0. 485 )、血磷(r=–0. 501) ,AKP( r=–0. 187 )、年龄(r=–0. 140 )水平相关,均P<0.01;与血钙(r =– 0. 084 )水平相关,P < 0. 05。结论 非透析CKD患者各骨代谢指标在CKD早期无明显差异,但随着肾功能的减退进行性升高,且其之间存在正相关关系。CKD患者普遍存在25(OH)D3的缺乏且在CKD早期即有。     

Factors affecting the response to erythropoiesis-stimulating agents

Recombinant human erythropoietin (rHuEPO) has transformed the management chronic renal failure (CKD) and considerably improved the outcome of patients on regular chronic dialysis. However, a significant number of patients fail to respond to high of Erythropoiesis-stimulating agents (ESAs) and several causes of inadequate response to epoetin therapy have been identified. Some factors, such as gender, age, length of time on dialysis, type of dialysis and co-morbidities such as hemoglobinopathy, are not susceptible to clinical intervention. However, many other factors can be adjusted. Iron deficiency, whether functional or absolute, is the most common factor that limits the response to rHuEPO. Monitoring of iron parameters and a large use of iron supplementation result in an efficient epoetin response. Infection and inflammation have been shown to reduce responsiveness to ESAs by disrupting iron metabolism and increasing the release of pro-inflammatory cytokines that inhibit erythropoiesis. Increase dialysis dose is associated with improvements in anemia correction and reduced requirements for ESAs. Severe hyperparathyroidism and aluminum overload lead to a reduced number of responsive erythroid progenitor cells. Finally, a number of nutritional factors, such as deficiencies of carnitine, vitamin B12, folic acid, and vitamin C, are susceptible to alter erythropoiesis. Optimizing patient response to ESAs therefore requires consideration of many of well-established factors and is important for both patient outcomes and cost of treatment.     

Risk factors of bone density disorder and vascular calcification in non-dialysis chronic kidney disease patients

Objective To explore the risk factors of bone density disorder and vascular calcification in non-dialysis chronic kidney disease (CKD) patients. Methods Clinical data of non-dialysis CKD patients who were admitted to the First Affiliated Hospital of Fujian Medical University between January 2013 and June 2014 were retrospectively analyzed. Using dual energy X-ray absorptiometry to evaluate their bone mineral density (BMD) and T value. Patients were divided into normal BMD group (T≥-1), osteopenia group (-2.5＜T＜-1) and osteoporosis group (T≤-2.5). The vascular calcification was evaluated by pectoral computed tomography. Multi-factor stepwise logistic regression analysis was used to assess the risk factors for low bone density and vascular calcification in non-dialysis CKD patients. Results A total of 337 non-dialysis CKD patients were enrolled. There were 110 (32.6%) patients with normal BMD, and 146(43.3%) patients with osteopenia, and 81(24.0%) patients with osteoporosis. Gender, history of hypertension, 25-hydroxy vitamin D and N-terminal osteocalcin shown statistical differences among three groups (all P＜0.05). The incidence rate of 25-hydroxy vitamin D deficiency shown statistical difference among three groups (P=0.012). Further, the rates were increased with the decreased bone mass (χ2=7.100, P=0.008). The other mineral bone disorders, such as hypocalcemia, hyperphosphatemia, low intact parathyroid hormone (iPTH) and high iPTH had no statistical difference among three groups (all P＞0.05). Multi-factor stepwise logistic regression analysis revealed that increased iPTH (OR=1.938), and low bone density (OR=1.724) were independent risk factors for CKD patients with vascular calcification (all P＜0.05), while women (OR=3.312) and vascular calcification (OR=1.742) were independent risk factors for CKD patients with low bone density (all P＜0.05). Conclusion Increased iPTH and low bone density are independent risk factors for non-dialysis CKD patients with vascular calcification, while women and vascular calcification are independent risk factors for non-dialysis CKD patients with low bone density.     

慢性肾脏病非透析患者脑钠素与动脉粥样硬化及心功能的关系

目的 研究脑钠素（BNP）与慢性肾脏病（CKD）非透析患者动脉粥样硬化及心功能不全的关系。 方法 采用双抗夹心免疫荧光法检测203例CKD非透析患者与16例高血压患者对照组全血BNP水平，分析其与颈动脉超声结果、心脏彩超结果及既往心血管疾病史的关系。 结果 CKD非透析患者BNP水平与对照组相比显著升高[M（范围）：54.40(15.10～ 173.00) ng/L比9.35(7.35～15.00) ng/L，P < 0.01]。Spearman相关分析显示CKD患者BNP与颈动脉内膜中层厚度（IMT）、左室心肌重量指数（LVMI）等呈正相关。存在颈动脉斑块、左室肥厚或既往发生过心血管事件的患者血BNP水平显著增高。多元回归分析显示LVMI、既往心血管事件均是影响BNP水平的独立因素。 结论 CKD非透析患者BNP水平和动脉粥样硬化性疾病、左室肥厚及心功能不全相关，提示BNP水平可作为一项评价CKD非透析患者心功能及动脉粥样硬化的敏感生物学指标。     

Serum endocan and circadian heart rate variability in non-dialysis stage 5 chronic kidney disease patients

Background

Chronic kidney disease (CKD) is very common now and is associated with high overall and cardiovascular mortality. Numerous studies have reported that elevated heart rate (HR) is a risk factor for cardiovascular mortality. We investigated the link between serum endocan and circadian heart rate variability in non-dialysis stage 5 CKD patients.

Methods

In a cross-sectional study, we enrolled 54 prevalent n non-dialysis stage 5 CKD patients (32 males, aged 48.2?±?14.92 years). HR was measured with an automatic system. Serum endocan level was analyzed by ELISA.

Results

Night/day HR ratio was independently predicted by serum endocan level (P?<?0.01) and hypertension history (P?<?0.05). Adjusted R² of the model was 0.222.

Conclusion

Increased serum endocan is significantly associated with circadian heart rate variability in non-dialysis stage 5 CKD patients. Further investigation is needed to explore the potential benefits of serum endocan lowering therapy in this patient group.

     

液相色谱质谱法对47例非透析慢性肾脏病患者色氨酸-犬尿氨酸通路的分析

目的利用液相色谱-质谱(LC-MS)代谢组学方法探讨慢性肾脏病(chronic kidney disease,CKD)1-4期非透析患者色氨酸(tryptophan, Trp)-犬尿氨酸(kynurenine, Kyn)通路的改变及意义。 方法2018年3月至2018年6月苏州大学附属第一医院肾内科CKD1～4期非透析患者47例,同期30例健康志愿者作为对照组。应用LC-MS法对受试者血浆进行代谢物分析。应用Human Metabolome Database (HMDB),MassBank,LipidMaps等数据库匹配不同CKD分期Kyn通路差异代谢物,绘制受试者曲线(receiver operating characteristic, ROC)评估差异代谢物敏感性与特异性。采用Metaboanalyst软件进行代谢通路拓扑分析。以Kyn/Trp比值(KT值)表示Kyn通路限速酶吲哚胺-2,3-双加氧酶(indoleamine-2,3-dioxygenase, IDO)活性。 结果Kyn在CKD2期即有明显升高(P<0.05),犬尿喹啉酸(kynurenine acid, KA)在CKD3期明显升高(P<0.01),二者随CKD分期增加呈上升趋势(P<0.01)。KT值在CKD2期即有升高(P<0.05),且随CKD分期增加呈上升趋势(P<0.01)。Trp代谢在CKD早期即出现紊乱。 结论Trp-Kyn通路在CKD早期即增强,Kyn、KA、IDO可能作为CKD早期诊断及进展的生物标志物。