Dosing patterns,drug costs,and hematologic outcome in anemic patients with chronic kidney disease switching from darbepoetin alfa to epoetin alfa

ABSTRACT

Objective: To compare real-world dosing patterns, drug costs, and hematologic outcome in anemic chronic kidney disease (CKD) patients, not receiving dialysis, who switched from darbepoetin alfa (DARB) to epoetin alfa (EPO) in a community practice setting.

Research design and methods: This retrospective observational chart review from a US nephrology clinic included 153 anemic CKD patients ≥ 18 years of age who did not receive dialysis during the study period, switched from DARB to EPO between 8/2003 and 8/2005, and received ≥ 2 doses of both agents. Paired t-test and McNemar's chi-square were performed comparing pre-switch and post-switch outcomes.

Results: Mean interval between doses increased from 24.3 ± 11.1 days with DARB to 28.8 ± 19.8 days with EPO (?p = 0.001). Weighted mean pre-switch weekly dose for DARB was 25?µg, while weighted mean post-switch weekly dose for EPO was 7090 Units, resulting in a dose ratio (Units EPO:µg DARB) of 287:1. These doses resulted in mean weekly costs of $110 (DARB) and $86 (EPO). Mean hemoglobin (Hb) levels increased over time from 10.8?g/dL at 6 months pre-switch to 11.1?g/dL 6 months after EPO initiation (?p = 0.0132). Mean Hb levels were > 11?g/dL, but below 12?g/dL, while patients received EPO.

Conclusions: Patients switching from DARB to EPO had a greater mean interval between doses, lower drug costs, and consistently maintained recommended Hb levels over time.

Limitations: The reverse direction (EPO to DARB) was not investigated. Although treatment outcomes were not assessed in a randomized, controlled setting, the study's observational nature provided actual evidence in a real-world setting.     

Dosing patterns, hematologic outcomes, and costs of erythropoietic agents in predialysis chronic kidney disease patients with anemia

OBJECTIVE: Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting. METHODS: This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for > or = 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24-week study period. RESULTS: A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (> or = Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (> or = 11 g/dL) (p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24-week cumulative doses were EPO 279 336 +/- 68 302 units and DARB 1084 +/- 246 microg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = 3400 US dollars, DARB = 4726 US dollars; FSS: EPO = 1528 US dollars, DARB = 2379 US dollars). CONCLUSIONS: Extended dosing (Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39-56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.     

The prevalence of anemia in patients with chronic kidney disease

SUMMARY

Objective: Anemia is a complication of chronic kidney disease and may contribute to adverse clinical outcomes. Early identification and treatment of anemia may improve cardiovascular morbidity and mortality. No large-scale population data are available specifically for patients with chronic kidney disease regarding prevalence of anemia, subpopulations at risk, and relationships between anemia and kidney function. This study was undertaken to address these questions in patients with chronic kidney disease, and investigate the relationship between anemia and glomerular filtration rate.

Research design and methods: Large-scale, cross-sectional, US multicenter survey; 5222 patients (mean age, 68.2?years; 46.6% male); 237 physician practices. Eligible patients: ≥ 18?years of age; serum creatinine: 1.5?mg/dL–6.0?mg/dL (females), 2.0?mg/dL–6.0?mg/dL (males).

Main outcome measures: Primary study end point: prevalence and severity of anemia (hemoglobin ≤ 12?g/dL). Data further stratified by hemoglobin (≤ 12?g/dL, ≤ 10?g/dL).

Results: Primary etiologies of chronic kidney disease (5222 evaluable patients): diabetes (49.5%); hypertension (33.0%). Glomerular filtration rate: < 60?mL/min/1.73?m² for 97.7% of evaluable patients. Mean ± SD serum creatinine level: 2.2?mg/dL ± 0.9?mg/dL; 2.5?mg/dL ± 1.0?mg/dL for males, 2.0?mg/dL ± 0.8?mg/dL for females. Mean ± SD hemoglobin: 12.2?g/dL ± 1.6?g/dL (47.7% had hemoglobin ≤ 12?g/dL; 8.9% had hemoglobin ≤ 10?g/dL). Prevalence of anemia was strongly associated with declining glomerular filtration rate. Percentage of patients with hemoglobin ≤ 12?g/dL increased from 26.7% to 75.5% when glomerular filtration rate decreased from ≥ 60?mL/min/1.73?m² to < 15?mL/min/1.73?m². Prevalence of hemoglobin ≤ 10?g/dL increased substantially from 5.2% to 27.2% when glomerular filtration rate diminished from ≥ 60?mL/min/1.73?m² to < 15?mL/min/1.73?m². After controlling for other patient characteristics associated with increased prevalence of anemia, the prevalence odds ratio for hemoglobin ≤ 10?g/dL was 0.54 (0.49–0.60) and for hemoglobin ≤ 12?g/dL was 0.68 (0.65–0.72), with each 10-mL/min/1.73?m² increase in glomerular filtration rate. Predictors of anemia: diabetes, female sex, and race/ethnicity.

Conclusions: Anemia was present in 47.7% of 5222 predialysis patients with chronic kidney disease. Prevalence of anemia increased as kidney function decreased. Certain subgroups are at increased risk for anemia.     

The relative dosing of epoetin alfa and darbepoetin alfa in chronic kidney disease

ABSTRACT

Objective: The purpose of this study was to review and analyze current research to evaluate the dose ratio of epoetin alfa and darbepoetin alfa for the treatment of anemia in chronic kidney disease (CKD) and to identify determinants of the variation in epoetin alfa: darbepoetin alfa dose ratios across studies.

Methods: A systematic review of the literature for comparative switch and non-switch studies of epoetin alfa and darbepoetin alfa treatments in CKD for the period 2000–2005 was performed. Two reviewers independently assessed the quality of the information. Data on the study design and outcomes were collected for each selected study. The dose ratio from epoetin alfa to darbepoetin alfa was calculated for each study, and the results were reported stratified by study characteristics. To control for differences in study design and characteristics that could explain the variability in the relative dosages of the two agents across studies, multivariate regression analysis was conducted. Based on these results, a dose conversion ratio for Canada was estimated.

Results: A total of 21 studies involving 16?378 patients exposed to epoetin alfa or darbepoetin alfa in CKD were identified. Univariate analysis of the dose ratios indicated a mean dose ratio of 217:1 (IU of epoetin alfa:µg of darbepoetin alfa). Results from the multivariate analysis demonstrated that the study design (i.e., switch study versus straight comparison studies) and geographical coverage (i.e., United States) affected the results. Based on the multivariate analysis, the dose conversion ratio between epoetin alfa and darbepoetin alfa for Canada was 169:1.

Conclusions: Despite limitations associated with switching studies and the limited total number of studies available, this systematic review based on aggregated results provides further evidence to the clinical community that the dose conversion ratio for epoetin alfa:darbepoetin alfa in CKD patients in Canada is approximately 169:1. At that ratio, treatment with epoetin alfa is 11–18% cheaper than treatment with darbepoetin alfa in Canada.     

A randomised,cross-over study comparing injection site pain with subcutaneous epoetin beta and subcutaneous darbepoetin alfa in patients with chronic kidney disease*

ABSTRACT

Objective: To compare injection site pain of subcutaneous (sc) epoetin beta and darbepoetin alfa in adult patients with chronic kidney disease.

Research design and methods: This was a multi-centre, randomised, two-arm, single-blind, cross-over study. Patients were randomised to receive weekly sc darbepoetin alfa 30?μg or weekly sc epoetin beta 6000?IU for 2 weeks and were then crossed over to the alternative treatment for 2 weeks. Injection site pain was assessed using a 10?cm ungraduated visual analogue scale (0?=?no pain, 10?=?worst pain) and a six-point verbal rating scale. Patient preference for treatment was also assessed.

Trial registration: http://clinicaltrials.gov/(NCT00377481).

Results: All randomised patients (N?=?48) completed the study. The sample comprised 29 chronic kidney disease patients (Stage 3 or Stage 4), 11 peritoneal dialysis patients and 8 renal transplant patients. Patients perceived significantly less pain with epoetin beta than darbepoetin alfa, using the visual analogue scale (relative pain score?=?2.75, darbepoetin alfa:epoetin beta, 95% CI: 1.85, 4.07; p?<?0.0001) and the verbal rating scale (median: 0.5, 95% CI: 0.5, 1.0 vs. median: 1.5, 95% CI: 1.0, 2.0; p?<?0.0001). Epoetin beta was preferred by significantly more patients (65%) than darbepoetin alfa (10%) (p?<?0.001); 25% of patients reported no preference.

Conclusions: Limitations included lack of an epoetin alfa comparator and limited blinding (patients were blinded to treatment, however, an unblinded nurse administered treatment). We show that sc injection of epoetin beta is significantly less painful than darbepoetin alfa and patient preference for epoetin beta confirms that the difference is clinically meaningful.     

The advantages of intravenous renal anaemia treatment in an undernourished patient with chronic kidney disease

SUMMARY

The subcutaneous (SC) treatment of renal anaemia in undernourished patients has potential limitations. In this case report we demonstrate the value of intravenous (IV) darbepoetin alfa in such a patient who experienced difficulty tolerating SC recombinant human erythropoietin (rHuEPO) therapy due to severe malnutrition. Intravenous treatment of renal anaemia in a malnourished patient is preferred because the absence of SC fat makes SC administration difficult. In such patients, darbepoetin alfa is the treatment of choice as it is administered less frequently than other erythropoietic therapies and yis more effective at maintaining target haemoglobin (Hb) concentrations. In contrast to rHuEPO, darbepoetin alfa also has the additional advantage of bioequivalent IV and SC dose requirements.     

Dosing patterns and treatment costs of erythropoietic agents in elderly patients with pre-dialysis chronic kidney disease in managed care organisations

OBJECTIVES: To investigate dosing patterns and drug costs of erythropoietic agents and assess the frequency of outpatient nephrologist visits in an elderly population with pre-dialysis chronic kidney disease (pCKD) newly initiated on epoetin alfa (EPO) or darbepoetin alfa (DARB). METHODS: An analysis of medical claims from more than 30 healthcare plans covering all census regions of the US in the period July 2002 through February 2005 was conducted. Patients were included if they were > or = 65 years of age, had at least one claim for CKD within 90 days prior to the initiation of any erythropoietic agent, were newly commenced on either EPO or DARB, and had received at least two treatment doses. If a patient received renal dialysis, data were censored 30 days prior to the first date of dialysis. Patients diagnosed with cancer or those who had undergone chemotherapy were excluded from the analysis. The average dosing interval for both EPO and DARB was calculated and classified as once weekly (qw), every 2 weeks (q2w) or every 3 weeks or less frequently (> or = q3w). Weighted average weekly doses were scaled based on treatment duration. The frequency of outpatient nephrologist visits was analysed. Average weekly treatment costs were calculated and presented using the May 2005 Wholesale Acquisition Costs. RESULTS: A total of 293 EPO and 102 DARB patients met the inclusion criteria. The two groups of patients had similar mean age (74.4 years for EPO vs 74.3 years for DARB) and gender distribution (47.4% female for EPO vs 51.0% for DARB). Extended dosing (every 2 weeks or less frequently: > or = q2w) during treatment was observed in both groups (EPO: qw 49.8%, q2w 31.7%, > or = q3w 18.4%; DARB: qw 19.6%, q2w 52.9%, > or = q3w 27.5%). The average dosing interval between injections was 13.6 days for the EPO group and 17.3 days for the DARB group. The weighted average weekly dose was 12,748 units for EPO and 43.5 microg for DARB. The average weekly erythropoietic treatment cost was significantly greater for DARB compared with EPO (190 US dollars vs 155 US dollars per week [2005 values]; p = 0.028). After controlling for covariates, the cost difference between the two groups was more pronounced and remained statistically significant (adjusted cost difference 41 US dollars/week higher for DARB patients; p = 0.013). The frequency of outpatient nephrologist visits during treatment was similar between the two groups (EPO 3.4 vs DARB 3.0 visits). CONCLUSIONS: Based on this analysis of claims data from more than 30 US healthcare plans, extended dosing (> or = q2w) of EPO and DARB was common in elderly pCKD patients treated with erythropoietic agents, with significantly higher weekly drug costs observed in the DARB group compared with the EPO group. The number of outpatient nephrologist visits was not significantly different between EPO and DARB patients. This study was the first to evaluate the dosing patterns of EPO and DARB in elderly pCKD patients in a large managed care population.     

Darbepoetin alfa for anemia in chronic kidney disease

Anemia of chronic kidney disease (CKD) is common, yet it is often under-recognized and undertreated, with serious adverse consequences. It is highly responsive to treatment with erythropoiesis-stimulating agents (ESAs). Darbepoetin alfa is a hyperglycosylated ESA that has a lower affinity to the erythropoietin receptor but a longer half-life than recombinant human erythropoietin, irrespective of administration by a subcutaneous or intravenous route. Owing to its pharmacokinetic characteristics, darbepoetin alfa has been used in extended dosing intervals ranging from once every week to once every 4 weeks in CKD patients on dialysis, as well as in CKD patients not on dialysis. Darbepoetin alfa has been shown to be safe and effective in clinical trials. The safety profile of darbepoetin alfa is similar to that of recombinant human erythropoietin. While target hemoglobin levels in CKD anemia remain debatable, treatment of anemia with ESAs has the proven benefits of reducing transfusions and improving quality of life. Darbepoetin alfa has the potential to simplify the treatment of CKD anemia with many advantages, including infrequent dosing, improved patient convenience and compliance, and decreased healthcare resource utilization.     

早期慢性肾脏病患者维生素D缺乏和贫血的相关性研究

目的探讨早期慢性肾脏病患者中维生素D缺乏与贫血间的关系。方法采用横断面调查研究的方法。分别用放射免疫检测法及全自动生化分析仪检测我院195例早期慢性肾脏病患者血清25羟基维生素D和1,25二羟基维生素D及血红蛋白水平,并比较不同维生素D水平组间的平均血红蛋白浓度及贫血患病率。结果受试对象平均血红蛋白浓度与25羟基维生素D(r=0.2146,P<0.01)及1,25二羟基维生素D(r=0.2479,P<0.01)浓度呈正相关。25羟基维生素D和1,25二羟基维生素D缺乏组与正常组相比,贫血的患病率增高。分层研究发现重度维生素D缺乏组贫血程度及血红蛋白水平降低更为明显。结论维生素D轴(1,25二羟基维生素D及25羟基维生素D)缺乏与低血红蛋白水平及贫血患病率相关。     

The association of darbepoetin alfa with hemoglobin and health-related quality of life in patients with chronic kidney disease not receiving dialysis

ABSTRACT

Objective: Anemia of chronic kidney disease (CKD) decreases patients’ health-related quality of life (HRQoL). The objective of this subanalysis was to determine the effect of every-other-week (Q2W) darbepoetin alfa on hemoglobin (Hb) levels and HRQoL measures in subjects with CKD who are naïve to erythropoiesis-stimulating agents (ESAs).

Methods: STAAR was a 52-week, multicenter, single-arm study. Subject inclusion criteria included: ≥?18?years of age and creatinine clearance ≤?70?mL/min or estimated glomerular filtration rate ≤?60?mL/min/1.73 m² but not receiving dialysis. Subjects included in this subanalysis were previously naïve to ESAs, had Hb <?11?g/dL, were initiated on subcutaneous Q2W darbepoetin alfa to achieve a Hb level not to exceed 12?g/dL, and had responses to at least one question on the KDQOL-CRI forms administered at baseline, week 12, and week 52.

Results: Of 911 ESA-naïve subjects enrolled in the study, 277 (30.4%) were included in this subanalysis. The majority of subanalysis subjects were Caucasian (63.2%) and/or women (54.5%). Mean Hb concentrations and all KDQOL-CRI scores improved significantly between baseline and week 12 (?p < 0.0001), and were maintained until week 52. Darbepoetin alfa was well tolerated.

Conclusions: Darbepoetin alfa initiated Q2W achieved and maintained Hb targets, and significantly improved and maintained HRQoL in study subjects with CKD. Limitations of the study must be considered when extrapolating these results to assess the benefits of treatment on HRQoL in the general CKD population.     

Validation of the BIACORE 3000 platform for detection of antibodies against erythropoietic agents in human serum samples

SUMMARY

Objective: To develop a validated BIACORE immunoassay for the detection and characterization of serum antibodies with specificity for erythropoietic molecules (e.g. darbepoetin alfa).

Methods: New Zealand White rabbits (n?=?8) were immunized by an intramuscular injection of darbepoetin alfa/adjuvant at 0,4,6, and 8 weeks. Serum was collected for 6 weeks after final injection and pooled for affinity purification. Antibody immunoassay measurements were performed using a BIACORE 3000 with darbepoetin alfa immobilized to the biosensor surface. Human serum samples were spiked with the affinity-purified rabbit antibody to develop and validate the BIACORE immunoassay.

Results: The assay was shown to be stable through 180 sample/regeneration cycles and had a threshold of 45.8 response units. The validated limit of detection was 0.40|ig/ml in 100% human serum. The method was robust, with variability not

exceeding a 20% coefficient of variation, well within acceptable limits for typical immunoassays.

Conclusion: All protein-based therapeutics have a potential for immunogenicity, and antibodies raised against these molecules may have important clinical sequelae. The biotechnology and pharmaceutical industries are challenged to address this potential by developing robust analytical platforms to detect and characterize antibodies directed against therapeutic proteins in clinical specimens. Traditionally, radioimmune precipitation assays and/or enzyme-linked immunoassays (ELISAs) are used for primary detection of host immune response; however, the BIACORE platform may be better suited for this purpose in many instances. This platform represents a robust tool that should be considered for the detection and characterization of antibodies directed against protein-based therapeutics.     

Efficacy and safety of CKD-11101 (darbepoetin-alfa proposed biosimilar) compared with NESP in anaemic chronic kidney disease patients not on dialysis

Objective: To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP® in treatment of anaemia in patients with chronic kidney disease not on dialysis. Clinical Trial Registration: NCT03431623.

Method: In this multi-centre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24?weeks, during which patients were treated every 2?weeks. All patients who completed the EEP were treated with CKD-11101 every 2?weeks for the first 4 weeks and every 4?weeks for the safety evaluation period (SEP), which was from 24?weeks to 52?weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb.

Results: The mean Hb level was increased in both groups during the EEP (both p?<?0.001). The difference in mean Hb level change between the two groups was 0.01?g/dL (95% CI = –0.213–0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was –1.40?mcg (95% CI = –6.859–4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group).

Conclusion: CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.     

慢性肾脏病对患者氧化应激程度的影响及可能意义

目的 探讨慢性肾脏病患者氧化应激的变化以及可能意义.方法 选择我院肾内科住院的慢性肾脏病患者73例,以同期我院体检中心47例体检健康者为对照组.收集受试者血和尿标本,分别用硫代巴比妥酸法和黄嘌呤氧化酶法测定脂质过氧化产物丙二醛和超氧化物歧化酶(SOD)的水平;同时收集患者临床资料,分析慢性肾脏病患者氧化应激程度的变化,同时探讨慢性肾脏病不同分期对氧化应激程度的影响.结果 慢性肾脏病组血丙二醛明显高于对照组[(16.7±20.3)μmol/L比(5.9±1.2)μmol/L,P＜0.05],尿丙二醛和对照组差异无统计学意义[(3.7±3.2)μmol/L比(5.2±4.5)μmol/L,P＞0.05].慢性肾脏病组血SOD和尿SOD活性分别为(37 300±18 200)U/L、(16 200±5600)U/L明显低于对照组[分别为(44 000±9400)U/L、(24 600±7200)U/L,均P＜0.05].结论 慢性肾脏病患者氧化应激程度明显增高,氧化应激随着肾功能的恶化而进一步加重.

Abstract：

Objective To study the oxidative stress in patients with chronic kidney disease (CKD) and its potential significance. Methods Seventy-three in-patients with CKD at the division of nephrology and 47 health controls were enrolled in this study between 2007 and 2010. The blood and urine samples were collected to detect malonaldehyde (MDA) and the activity of superoxide dismutase (SOD). Meanwhile the clinical datum was analyzed to evaluate the impact of CKD on oxidative stress. Results Serum MDA dramatically increased in patients with CKD than that in controls [( 16.7 ± 20.3 ) μmol/L vs ( 5.9 ± 1.2 ) μmol/L,P ＜ 0.05], while SOD of serum and urine in CKD group decreased significantly compared with controls [(37 300 ± 18 200) U/L vs (44 000 ±9 400) U/L, ( 16200 ± 5 600) U/L vs ( 24 600 ± 7 200) U/L, P ＜ 0.05].. Conclusion Oxidative stress is enhanced in patients CKD and it aggravates with the deterioration of kidney function.     

Clinical and economic comparison of epoetin alfa and darbepoetin alfa

SUMMARY

Background: The pharmacoeconomics of erythropoietic therapy for the treatment of anemia is receiving renewed attention due to the current availability of two agents. Epoetin alfa has been the standard of therapy for patients with renal disease and cancer-related anemia for more than a decade. Darbepoetin alfa, an alternative agent, is now approved for anemia resulting from renal disease and cancer chemotherapy.

Methodology: Although direct comparative trials have not been performed with these agents, information published in the last several years regarding their clinical efficacy, safety, and dosing is sufficient, in most cases, to compare costs. With the disclaimer that any efficacy comparison of competing products using published reports has certain limitations, a cost-minimization approach from a provider's perspective was conducted.

Results:To provide background for the economic evaluation, pharmacokinetic and pharmacodynamic data for these two agents are discussed. Recent clinical trials in the nephrology and oncology therapeutic areas are summarized, highlighting study designs, dosing regimens, patient entry criteria, study endpoints, and published results. Cost data, based on average wholesale prices (AWP) in 2003, are compared and calculated from available clinical data with an emphasis on efficacy.

Conclusion: These evaluations largely conclude that epoetin alfa is the better pharmacoeconomic value of the two currently available erythropoietic agents.     

慢性肾病患者颈动脉粥样硬化的临床分析

目的研究慢性肾病(CKD)患者颈动脉的结构、形态及血流动力学。方法将168例CKD患者根据肾小球滤过率(GFR)分为CKD2-3期组(59例)、CKD4期组(52例)和CKD5期组(57例),彩色多普勒超声检测双侧颈总动脉的内-中膜厚度(IMT)、收缩期血流峰值流速(Vmax)、舒张期血流峰值流速(Vmin)、有无斑块,计算阻力指数(RI)。根据CKD患者有无糖尿病、粥样斑块分组进行数据分析。结果 CKD4期患者的IMT和斑块检出率高于CKD2-3期患者(P<0.05或P<0.01);CKD5期患者的IMT和斑块检出率高于CKD2-3期(P<0.01)和CKD4期患者(P<0.05),Vmax、Vmin较CKD2-3期患者低(P<0.05)。糖尿病组的年龄、IMT和斑块检出率高于非糖尿病组(P<0.01),Vmax、Vmin降低(P<0.05)。颈动脉斑块阳性组的年龄和IMT较斑块阴性组高(P<0.01),GFR、Vmax、Vmin明显低(P<0.05)。结论 CKD患者随着肾功能的恶化和年龄的增高,动脉粥样硬化逐渐加重,并出现相应的血液动力学改变;糖尿病是动脉粥样硬化加重的重要因素。     

慢性肾脏病患者蛋白质-能量消耗研究新进展

蛋白质-能量消耗在慢性肾脏病患者中发病率较高,临床上主要表现为饮食摄入、生化指标、体重指数、肌肉质量等方面的异常,其发病机制非常复杂,跟摄入不足、炎症、代谢性酸中毒、激素水平紊乱、透析相关因素等有关,严重影响透析患者的预后,因此早期发现、诊断和防治显得非常重要,将营养评估列入慢性肾脏病患者诊疗的日常工作当中,并对照诊断标准,及早诊断和采取各种措施防治蛋白质-能量消耗,最终提高慢性肾脏病患者的预后和生存率.本文对慢性肾脏病引起的蛋白质-能量消耗流行病学特点、发病机理、评估方式、治疗及干预措施等进行阐述.     

Pharmacokinetic/pharmacodynamic modeling of roxadustat's effect on LDL cholesterol in patients in Japan with dialysis-dependent chronic kidney disease and anemia

AimsThe objective of this analysis was to develop and evaluate a pharmacokinetic/pharmacodynamic (PK/PD) model of the effect of roxadustat on low-density lipoprotein cholesterol (LDL-C) in Japanese patients with anemia of dialysis-dependent chronic kidney disease while considering the impact of covariates on model parameters.MethodsA total of 2330 LDL-C measurements from 275 patients in 3 clinical studies were analyzed using a nonlinear-mixed effects modeling approach in NONMEM software.ResultsThe PK/PD relationship between roxadustat exposure and LDL-C was well described by a kinetic-pharmacodynamic model with a physiological indirect response model as the PD component. Co-administered statin usage, sevelamer usage, type of dialysis (hemodialysis or peritoneal dialysis), and sex were selected as covariates for LDL_baseline. Weight was selected as a covariate for ID_50. I_max and ID₅₀ were estimated as 0.661 and 1.51 mg/h, respectively.ConclusionRoxadustat can decrease LDL-C independent of statins and sevelamer. Further study of the ability of roxadustat to lower LDL-C and any potential effects on outcomes is needed.     

Population pharmacokinetics of darbepoetin alfa in peritoneal dialysis and non-dialysis patients with chronic kidney disease after single subcutaneous administration

Objective  To characterize the pharmacokinetics of darbepoetin alfa and covariate relationships in chronic kidney disease (CKD) patients after a single subcutaneous administration. Methods  A total of 989 serum concentration recordings from 64 patients were analyzed using NONMEM with a model including endogenous erythropoietin production. The basic and final models were evaluated for stability using bootstrapping. Results  The selected basic model had one-compartment with a combination of the additive and constant coefficient of variation error models for residual variability. The significant covariate was weight for apparent clearance (CL/f) and apparent volume of central compartment (V₁/f). The typical values of CL/f, V₁/f, and absorption rate constant were 0.158 l/h, 13.7 l, and 0.0376/h, respectively. Evaluation by bootstrapping showed that the final model was stable. Conclusion  The present analysis indicated that weight is a significant covariate for CL/f and V₁/f. However, dosage adjustment according to weight is not necessary for subcutaneous administration of darbepoetin alfa in CKD patients.     

Epoetin delta is effective for the management of anaemia associated with chronic kidney disease

ABSTRACT

Objective: To demonstrate the efficacy and safety of epoetin delta for the treatment of anaemia in dialysis patients with chronic kidney disease (CKD).

Research design and methods: This was a 12‐week, randomized, double-blind, active-comparator study. CKD patients who were naïve to epoetin treatment and had haemoglobin < 10?g/dL were randomized to epoetin delta 15, 50, 150, or 300 IU/kg or epoetin alfa 50 IU/kg. Patients initially entered a correction phase until they recorded haemoglobin of ≥ 11.5?g/dL for two consecutive weekly measurements or one haemoglobin measurement of ≥ 13?g/dL (correction success). A maintenance phase followed where the dose was adjusted to maintain haemoglobin ≥ 10.5?g/dL. Maintenance success was defined as haemoglobin > 10.5?g/dL at Week 12. Total success was defined as achieving maintenance and correction success.

Main outcome measures: The primary objective was to demonstrate that the proportion of patients achieving total success was greater in the pooled 150?IU/kg and 300?IU/kg groups compared with the 15?IU/kg dose group.

Results: Total success was achieved in 55.6% of patients in the pooled highest epoetin delta group compared with 4.5% in the lowest dose group. There was no significant difference in total success for the epoetin delta and epoetin alfa 50?IU/kg groups. Significant increases in haemoglobin and haematocrit levels were observed in the 150 and 300?IU/kg dose groups. Adverse events occurred at frequencies expected for this patient group.

Conclusions: Epoetin delta was effective in increasing haemoglobin levels in patients with baseline haemoglobin of < 10?g/dL.