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当前时代铝积累对骨骼和心血管风险的影响。

Effect of aluminum accumulation on bone and cardiovascular risk in the current era.

机构信息

Nephrology Division, School of Medical Sciences, University of Campinas (Unicamp), Campinas, Brazil.

Laboratory for Evaluation of Mineral and Bone Metabolism in Nephrology (LEMON), School of Medical Sciences, University of Campinas (Unicamp), Campinas, Brazil.

出版信息

PLoS One. 2023 Apr 20;18(4):e0284123. doi: 10.1371/journal.pone.0284123. eCollection 2023.

Abstract

BACKGROUND

The prevalence of aluminum (Al) intoxication has declined over the past 3 decades. However, different groups still report on the diagnosis of Al in bone. Prolonged and low-intensity exposures to Al may not be captured by serum Al measurements, preventing its proper diagnosis. We hypothesize that bone Al accumulation may be related to bone and cardiovascular events in the current Era.

AIMS

To detect the diagnosis of bone Al accumulation; to explore bone and cardiovascular consequences of Al accumulation.

METHODS

This is a sub-analysis of The Brazilian Registry of Bone Biopsy, a prospective, multicentre cohort, with a mean follow-up of 3.4 years, including patients with CKD undergoing bone biopsy; bone fracture and major cardiovascular events (MACE) were adjudicated; Al accumulation was identified by solochrome-azurine staining; history of previous Al accumulation was registered based on information provided by the nephrologist who performed the bone biopsy; bone histomorphometry parameters, clinical data, and general biochemistry were registered.

RESULTS

275 individuals were considered; 96 (35%) patients have diagnosed with bone Al accumulation and were younger [50 (41-56) vs. 55 (43-61) years; p = 0.026], had lower body mass index [23.5 (21.6-25.5) vs. 24.3 (22.1-27.8) kg/m2; p = 0.017], higher dialysis vintage [108 (48-183) vs. 71 (28-132) months; p = 0.002], presented pruritus [23 (24%) vs. 20 (11%); p = 0.005], tendon rupture [7 (7%) vs. 3 (2%); p = 0.03) and bone pain [2 (0-3) vs. 0 (0-3) units; p = 0.02]. Logistic regression reveals that prior bone Al accumulation [OR: 4.517 (CI: 1.176-17.353); p = 0.03] and dialysis vintage [OR: 1.003 (CI: 1.000-1.007); p = 0.046] as independent determinants of bone Al accumulation; minor perturbations in dynamic bone parameters and no differences in bone fractures rate were noted; MACE was more prevalent in patients with bone Al accumulation [21 (34%) vs. 23 (18%) events; p = 0.016]. Cox regression shows the actual/prior diagnosis of bone Al accumulation and diabetes mellitus as independent predictors for MACE: [HR = 3.129 (CI: 1.439-6.804; p = 0.004) and HR = 2.785 (CI: 1.120-6.928; p = 0.028].

CONCLUSIONS

An elevated proportion of patients have bone Al accumulation, associated with a greater prevalence of bone pain, tendon rupture, and pruritus; bone Al accumulation was associated with minor perturbations in renal osteodystrophy; actual/prior diagnosis of bone Al accumulation and diabetes mellitus were independent predictors for MACE.

摘要

背景

在过去的 30 年中,铝(Al)中毒的患病率有所下降。然而,仍有不同的研究小组报告了骨骼中的 Al 诊断情况。长期、低强度的 Al 暴露可能不会被血清 Al 测量所捕捉到,从而无法对其进行正确诊断。我们假设在当前时代,骨骼 Al 积累可能与骨骼和心血管事件有关。

目的

检测骨骼 Al 积累的诊断;探索 Al 积累与骨骼和心血管后果的关系。

方法

这是巴西骨活检登记处的一项亚分析,这是一项前瞻性、多中心队列研究,平均随访 3.4 年,包括接受骨活检的慢性肾脏病患者;对骨折和主要心血管事件(MACE)进行了裁决;通过茜素蓝染色检测 Al 积累;根据进行骨活检的肾病学家提供的信息,记录了先前 Al 积累的病史;登记了骨组织形态计量学参数、临床数据和一般生化数据。

结果

共纳入 275 名个体;96 名(35%)患者被诊断为骨骼 Al 积累,他们更年轻[50(41-56)岁 vs. 55(43-61)岁;p=0.026],体重指数较低[23.5(21.6-25.5)kg/m2 vs. 24.3(22.1-27.8)kg/m2;p=0.017],透析时间更长[108(48-183)个月 vs. 71(28-132)个月;p=0.002],有瘙痒[23 名(24%) vs. 20 名(11%);p=0.005]、肌腱断裂[7 名(7%) vs. 3 名(2%);p=0.03]和骨痛[2 名(0-3)分 vs. 0 名(0-3)分;p=0.02]。逻辑回归显示,先前的骨骼 Al 积累[比值比:4.517(95%置信区间:1.176-17.353);p=0.03]和透析时间[比值比:1.003(95%置信区间:1.000-1.007);p=0.046]是骨骼 Al 积累的独立决定因素;动态骨骼参数的轻微改变和骨折发生率无差异;骨骼 Al 积累的患者 MACE 更常见[21 名(34%)vs. 23 名(18%)事件;p=0.016]。Cox 回归显示,实际/先前的骨骼 Al 积累诊断和糖尿病是 MACE 的独立预测因素:[风险比=3.129(95%置信区间:1.439-6.804;p=0.004)和风险比=2.785(95%置信区间:1.120-6.928;p=0.028]。

结论

大量患者有骨骼 Al 积累,与更多的骨痛、肌腱断裂和瘙痒有关;骨骼 Al 积累与肾脏骨营养不良的轻微改变有关;实际/先前的骨骼 Al 积累诊断和糖尿病是 MACE 的独立预测因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ade9/10118170/83b73e20af2b/pone.0284123.g001.jpg

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