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人群队列研究中血铅水平与肾功能下降的关系

Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort.

机构信息

Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, Gothenburg, Sweden.

Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, Gothenburg, Sweden.

出版信息

Am J Kidney Dis. 2018 Sep;72(3):381-389. doi: 10.1053/j.ajkd.2018.02.358. Epub 2018 Apr 23.

Abstract

BACKGROUND

Environmental lead exposure has been associated with decreased kidney function, but evidence from large prospective cohort studies examining low exposure levels is scarce. We assessed the association of low levels of lead exposure with kidney function and kidney disease.

STUDY DESIGN

Prospective population-based cohort.

SETTING & PARTICIPANTS: 4,341 individuals aged 46 to 67 years enrolled into the Malmö Diet and Cancer Study-Cardiovascular Cohort (1991-1994) and 2,567 individuals subsequently followed up (2007-2012).

PREDICTOR

Blood lead concentrations in quartiles (Q1-Q4) at baseline.

OUTCOMES

Change in estimated glomerular filtration rate (eGFR) between the baseline and follow-up visit based on serum creatinine level alone or in combination with cystatin C level. Chronic kidney disease (CKD) incidence (185 cases) through 2013 detected using a national registry.

MEASUREMENTS

Multivariable-adjusted linear regression models to assess associations between lead levels and eGFRs at baseline and follow-up and change in eGFRs over time. Cox regression was used to examine associations between lead levels and CKD incidence. Validation of 100 randomly selected CKD cases showed very good agreement between registry data and medical records and laboratory data.

RESULTS

At baseline, 60% of study participants were women, mean age was 57 years, and median lead level was 25 (range, 1.5-258) μg/L. After a mean of 16 years of follow-up, eGFR decreased on average by 6mL/min/1.73m (based on creatinine) and 24mL/min/1.73m (based on a combined creatinine and cystatin C equation). eGFR change was higher in Q3 and Q4 of blood lead levels compared with Q1 (P for trend = 0.001). The HR for incident CKD in Q4 was 1.49 (95% CI, 1.07-2.08) compared with Q1 to Q3 combined.

LIMITATIONS

Lead level measured only at baseline, moderate number of CKD cases, potential unmeasured confounding.

CONCLUSIONS

Low-level lead exposure was associated with decreased kidney function and incident CKD. Our findings suggest lead nephrotoxicity even at low levels of exposure.

摘要

背景

环境铅暴露与肾功能下降有关,但来自于大型前瞻性队列研究的低暴露水平证据很少。我们评估了低水平铅暴露与肾功能和肾脏疾病的关系。

研究设计

前瞻性人群为基础的队列研究。

研究场所和参与者

1991 年至 1994 年间,4341 名年龄在 46 至 67 岁之间的人参加了马尔默饮食与癌症研究 - 心血管队列(Malmö Diet and Cancer Study-Cardiovascular Cohort),其中 2567 人随后进行了随访(2007 年至 2012 年)。

预测因素

基线时血铅浓度四分位数(Q1-Q4)。

结局

基于血清肌酐水平或肌酐和胱抑素 C 水平组合,评估基线和随访时 eGFR 的变化。通过国家登记处发现,2013 年之前(185 例)慢性肾脏病(CKD)的发生率。

测量方法

多变量调整线性回归模型,评估基线和随访时铅水平与 eGFR 之间的关系,以及随时间变化的 eGFR 变化。Cox 回归用于检查铅水平与 CKD 发生率之间的关系。对 100 例随机选择的 CKD 病例的验证表明,登记处数据与医疗记录和实验室数据之间有很好的一致性。

结果

基线时,60%的研究参与者为女性,平均年龄为 57 岁,中位血铅水平为 25(范围,1.5-258)μg/L。平均随访 16 年后,eGFR 平均下降 6mL/min/1.73m(基于肌酐)和 24mL/min/1.73m(基于肌酐和胱抑素 C 方程)。与 Q1 相比,Q3 和 Q4 的血铅水平与 eGFR 变化更高(趋势 P 值=0.001)。与 Q1 至 Q3 相比,Q4 的 CKD 发生率 HR 为 1.49(95%CI,1.07-2.08)。

局限性

仅在基线时测量铅水平,CKD 病例数适中,可能存在未测量的混杂因素。

结论

低水平铅暴露与肾功能下降和 CKD 发病有关。我们的研究结果表明,即使在低暴露水平下,铅也具有肾毒性。

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