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维生素D缺乏——接受血液透析治疗的终末期糖尿病肾病患者的预后标志物还是死亡风险因素——一项前瞻性多中心研究

Vitamin D deficiency--prognostic marker or mortality risk factor in end stage renal disease patients with diabetes mellitus treated with hemodialysis--a prospective multicenter study.

作者信息

Schiller Adalbert, Gadalean Florica, Schiller Oana, Timar Romulus, Bob Flaviu, Munteanu Mircea, Stoian Dana, Mihaescu Adelina, Timar Bogdan

机构信息

Department of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.

B Braun Avitum Dialysis Center Timisoara, Timisoara, Romania.

出版信息

PLoS One. 2015 May 12;10(5):e0126586. doi: 10.1371/journal.pone.0126586. eCollection 2015.

Abstract

BACKGROUND

End stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM.

METHODS

Our prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than 12 ng/mL.

RESULTS

Patients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM.

CONCLUSIONS

ESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy.

摘要

背景

与非糖尿病患者相比,接受肾脏替代治疗(RRT)的终末期肾病(ESRD)合并糖尿病(DM)患者死亡率更高,维生素D缺乏症的患病率也更高。维生素D缺乏是否是这些患者死亡的危险因素或预后标志物仍存在争议。本研究调查了糖尿病血液透析(HD)患者中维生素D缺乏的患病率及其对全因死亡率的影响。

方法

我们的前瞻性非干预队列研究纳入了600例接受血液透析治疗(HD)的患者(年龄中位数为56岁,四分位间距为19岁,男性332例(55.3%)),这些患者来自罗马尼亚所有主要地理区域的7个HD中心。DM的患病率为15.3%。然后对他们进行随访,内容包括:透析时间、透析效率、肾性贫血、慢性肾脏病-矿物质和骨异常(CKD-MBD)、炎症状态和合并症:冠状动脉疾病(CAD)、外周血管疾病(PVD)和中风。25-羟维生素D缺乏定义为低于12 ng/mL的值。

结果

患者随访3年。总体3年死亡率为25.5%(153例),糖尿病患者的死亡率高于非糖尿病患者(33.7%对24.0%;P = 0.049)。生存分析显示,DM的存在也影响时间相关预后,DM透析患者死亡的风险比(HR)为1.52 [1.03至2.26],95%置信区间,P = 0.037。在糖尿病患者中,25-羟维生素D缺乏显著更高(37.0%对24.0%,P = 0.009)。此外,在糖尿病患者中,我们观察到透析时间较短(2年对3年,P<0.001)和完整甲状旁腺激素(iPTH)较低(258.0 pg/ml对441.9 pg/ml,P = 0.002)。关于纳入研究时合并症的存在情况,透析患者中糖尿病的存在与CAD患病率增加相关(87.0%对58.1%,P<0.001)、PVD患病率增加相关(67.4%对17.3%,P<0.001)和中风病史患病率增加相关(29.3%对14.0%,P<0.001)。在糖尿病患者中,25-羟维生素D缺乏会增加死亡概率(50.0%对24.1%;P = 0.011)。在多因素Cox比例风险分析中,维生素D缺乏仍然是糖尿病透析患者死亡的独立预测因素(HR = 1.71,95%置信区间1.21至2.43,P = 0.003)。同时,多因素Cox比例风险分析显示,年龄(每增加一岁HR = 1.02,P = 0.004)、CAD(HR = 1.55,P = 0.046)和PVD(HR = 1.50,P = 0.029)是糖尿病透析患者死亡的独立预测因素。

结论

接受HD治疗的ESRD合并DM患者的总体死亡率高于非糖尿病患者。维生素D缺乏在HD合并DM患者中更为普遍。低25-羟维生素D水平与这些患者全因死亡率增加相关。根据我们的数据,对于HD合并DM患者,筛查维生素D缺乏(并进行纠正)对于优化风险降低策略应是强制性的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f83/4428845/5794430e8eb1/pone.0126586.g001.jpg

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