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  • 1
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Chronic kidney disease (CKD) is a major public health issue worldwide including in China. One of the most common complication in advanced Chronic kidney disease (CKD) is secondary hyperparathyroidism (SHPT). Reports show higher risk of bone fracture, cardiovascular events and all-cause mortality is associated with uncontrolled SHPT in patients with CKD. Cinacalcet, a calcimimetic agent was reported to reduce iPTH levels without Ca increase in patients with SHPT previously. However there has been no large-cohort study and stratified analysis of cinacalcet based on the level of iPTH in China. Moreover, the optimal therapeutic doses of cinacalcet with mild-to-severe SHPT is remaining unknown. ACTIVE study is an IV, open-label, multicenter clinical trial aimed to: (1) evaluate the efficacy and safety of cinacalcet in maintenance hemodialysis patients with mild-to-severe SHPT; (2) explore optimal combinations therapy with cinacalcet and other agents for treating patients with CKD-mineral and bone disorder. (3) investigate the benefit of long-term, continuous medication with cinacalcet in the real-world setting. Method The study design was reported on 2019 ASN. Key inclusion criteria were a baseline iPTH ≥300 pg/mL with life expectancy of ≥2 years, and ≥12 weeks of maintenance dialysis (three dialysis sessions per week) prior to enrollment. The enrollments were grouped based on their iPTH level as having mild (300-600 pg/mL), moderate (600-900 pg/mL) or severe (≥900 pg/mL). Patients initiated treatment with cinacalcet orally at a starting dose of 25 mg once daily (qd). The primary efficacy endpoint is the proportion of patients achieving iPTH targets (iPTH between 150-300pg/mL) at 20 and 32 weeks after the initiation of cinacalcet treatment. Adverse events and serious adverse events were recorded. An interim analysis was scheduled as 375 patients completed 32 weeks visit. Results 911 patients were recruited and of 750 eligible patients, 275 were identified as mild, 224 were considered as moderate and left 251 were grouped as severe SHPT. The study flowchart of 375 patients including mild(127), moderate(106) and severe(142) SHPT for interim analysis was shown in Fig 1. The baseline results including demographic and biomarkers level were reported on 2019 ASN. After 4 weeks’ cinacalcet treatment, serum PTH decreased in all three group, while extremely remarkable in the severe SHPT group. Interim analysis results revealed that the proportion of patients achieving iPTH target (150-300 pg/mL) at 20 wk visit among mild, moderate and severe groups were 38.61% (39/101), 30.11% (28/93) and 10.91% (12/110) respectively. The proportion of patients achieving iPTH target at 32 wk visit in 3 groups increased to 44.68% (42/94), 27.27% (24/88) and 14.56% (15/103) respectively (Table.1). The trends of the proportion of patients achieving iPTH target increased in all 3 different groups (Fig.2). The safety analysis showed the most common treatment-related AE in top 3 including hypocalcemia, hyperlipidemia, and loss of appetite. In vital signs, electrocardiogram (ECG) and laboratory examination of descriptive analysis, found no obvious safety tips. This study is sponsored by Kyowa Hakko Kirin (China) Pharmaceutical Co., Ltd. The analysis is still ongoing and results will be released at EDTA meeting this year. Conclusion Oral cinacalcet HCl was effective and safe in reducing iPTH in patients receiving HD with mild-to-severe SHPT.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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    detail.hit.zdb_id: 90594-X
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  • 2
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 5 ( 2023-05-01), p. e2310909-
    Abstract: Baseline findings from the China Dialysis Calcification Study (CDCS) revealed a high prevalence of vascular calcification (VC) among patients with end-stage kidney disease; however, data on VC progression were limited. Objectives To understand the progression of VC at different anatomical sites, identify risk factors for VC progression, and assess the association of VC progression with the risk of cardiovascular events and death among patients receiving maintenance dialysis. Design, Setting, and Participants This cohort study was a 4-year follow-up assessment of participants in the CDCS, a nationwide multicenter prospective cohort study involving patients aged 18 to 74 years who were undergoing hemodialysis or peritoneal dialysis. Participants were recruited from 24 centers across China between May 1, 2014, and April 30, 2015, and followed up for 4 years. A total of 1489 patients receiving maintenance dialysis were included in the current analysis. Data were analyzed from September 1 to December 31, 2021. Exposures Patient demographic characteristics and medical history; high-sensitivity C-reactive protein laboratory values; serum calcium, phosphorus, and intact parathyroid hormone (iPTH) values; and previous or concomitant use of medications. Main Outcomes and Measures The primary outcome was progression of VC at 3 different anatomical sites (coronary artery, abdominal aorta, and cardiac valves) and identification of risk factors for VC progression. Participants received assessments of coronary artery calcification (CAC), abdominal aortic calcification (AAC), and cardiac valve calcification (CVC) at baseline, 24 months, 36 months, and 48 months. Secondary outcomes included (1) the association between VC progression and the risk of all-cause death, cardiovascular (CV)–related death, and a composite of all-cause death and nonfatal CV events and (2) the association between achievement of serum calcium, phosphorus, and iPTH target levels and the risk of VC progression. Results Among 1489 patients, the median (IQR) age was 51.0 (41.0-60.0) years; 59.5% of patients were male. By the end of 4-year follow-up, progression of total VC was observed in 86.5% of patients; 69.6% of patients had CAC progression, 72.4% had AAC progression, and 33.4% had CVC progression. Common risk factors for VC progression at the 3 different anatomical sites were older age and higher fibroblast growth factor 23 levels. Progression of CAC was associated with a higher risk of all-cause death (model 1 [adjusted for age, sex, and body mass index]: hazard ratio [HR] , 1.97 [95% CI, 1.16-3.33]; model 2 [adjusted for all factors in model 1 plus smoking status, history of diabetes, and mean arterial pressure] : HR, 1.89 [95% CI, 1.11-3.21]; model 3 [adjusted for all factors in model 2 plus calcium, phosphorus, intact parathyroid hormone, and fibroblast growth factor 23 levels and calcium-based phosphate binder use] : HR, 1.92 [95% CI, 1.11-3.31]) and the composite of all-cause death and nonfatal CV events (model 1: HR, 1.98 [95% CI, 1.19-3.31] ; model 2: HR, 1.91 [95% CI, 1.14-3.21]; model 3: HR, 1.95 [95% CI, 1.14-3.33] ) after adjusting for all confounding factors except the presence of baseline calcification. Among the 3 targets of calcium, phosphorus, and iPTH, patients who achieved no target levels (model 1: odds ratio [OR], 4.75 [95% CI, 2.65-8.52] ; model 2: OR, 4.81 [95% CI, 2.67-8.66]; model 3 [for this analysis, adjusted for all factors in model 2 plus fibroblast growth facto r 23 level and calcium-based phosphate binder use]: OR, 2.76 [95% CI, 1.48-5.16] ), 1 target level (model 1: OR, 3.71 [95% CI, 2.35-5.88]; model 2: OR, 3.62 [95% CI, 2.26-5.78] ; model 3: OR, 2.19 [95% CI, 1.33-3.61]), or 2 target levels (model 1: OR, 2.73 [95% CI, 1.74-4.26] ; model 2: OR, 2.69 [95% CI, 1.71-4.25]; model 3: OR, 1.72 [95% CI, 1.06-2.79] ) had higher odds of CAC progression compared with patients who achieved all 3 target levels. Conclusions and Relevance In this study, VC progressed rapidly in patients undergoing dialysis, with different VC types associated with different rates of prevalence and progression. Consistent achievement of serum calcium, phosphorus, and iPTH target levels was associated with a lower risk of CAC progression. These results may be useful for increasing patient awareness and developing appropriate strategies to improve the management of chronic kidney disease–mineral and bone disorder among patients undergoing dialysis.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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