Rationale & Objective

Chronic kidney disease (CKD), defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², is a risk factor for cardiovascular morbidity and mortality. Little is known about low birth weight and risk for CKD in middle-aged adults in the general population. We estimated the causal association between birth weight and eGFR in a Dutch cohort of middle-aged men and women.

Study Design

Retrospective cohort study.

Setting & Participants

6,671 participants in the Netherlands Epidemiology of Obesity (NEO) Study. Replication study using data for 133,814 participants studied by the CKDGen consortium.

Exposure

Birth weight was self-reported and also based on an instrumental variable, 59 birth weight–associated genetic variants, derived from an independent data source.

Outcome

eGFR at the age of 45 to 65 years.

Analytical Approach

We assessed the association between self-reported birth weight and eGFR in the NEO Study using multivariable linear regression, adjusted for age, sex, education, smoking, and alcohol use. The effect of the instrument on eGFR was estimated using separate 2-sample Mendelian randomization analyses: one using individual data from the NEO cohort and one using summary data from the CKDGen consortium.

Results

At baseline, mean eGFR was 86 ± 12.4 (SD) mL/min/1.73 m². After multivariable adjustment, self-reported birth weight was not associated with kidney function in middle age. Two-sample Mendelian randomization analysis showed that in the NEO cohort, for each 500-g lower birth weight defined using genetic variants, there was a 3.7 (95% CI, 0.5-6.9)–mL/min/1.73 m² lower eGFR at the age of 45 to 65 years. However, using CKDGen summary-level data, there was a smaller nonsignificant relationship between birth weight and eGFR.

Limitations

Birth weight was self-reported.

Conclusions

Lower birth weight defined using genetic variants was associated with lower eGFRs in Dutch middle-aged adults. However, this finding was not replicated within the CKDGen consortium.

中文翻译：

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中年男女低出生体重和肾脏功能：肥胖症荷兰流行病学研究

理由与目标

慢性肾病（CKD），定义为估计的肾小球滤过率（eGFR）<60 mL / min / 1.73 m ²，是心血管疾病发病率和死亡率的危险因素。对普通人群中年成年人的低出生体重和CKD风险知之甚少。我们估计了荷兰中年男女队列中出生体重和eGFR之间的因果关系。

学习规划

回顾性队列研究。

设置与参与者

荷兰肥胖病流行病学（NEO）研究的6,671名参与者。使用CKDGen联盟研究的133,814名参与者的数据进行复制研究。

接触

出生体重是自我报告的，也是基于一个工具变量，即59个与出生体重相关的遗传变异，这些变异来自独立的数据来源。

结果

eGFR年龄在45至65岁之间。

分析方法

在NEO研究中，我们使用多元线性回归评估了自我报告的出生体重与eGFR之间的相关性，并根据年龄，性别，受教育程度，吸烟和饮酒情况进行了调整。使用单独的2样本孟德尔随机分析来评估该仪器对eGFR的影响：一种使用来自NEO队列的单独数据，另一种使用来自CKDGen联盟的摘要数据。

结果

在基线时，平均eGFR为86±12.4（SD）mL / min / 1.73 m ²。经过多变量调整后，自我报告的出生体重与中年人的肾功能无关。孟德尔随机抽样的两个样本显示，在NEO队列中，使用遗传变异定义的每500 g出生体重低者，eGFR降低3.7（95％CI，0.5-6.9）–mL / min / 1.73 m ²年龄在45至65岁之间。但是，使用CKDGen摘要级别的数据，出生体重和eGFR之间的关系较小，但不显着。

局限性

出生体重是自我报告的。

结论

使用遗传变异定义的较低出生体重与荷兰中年成年人较低的eGFR相关。但是，此发现未在CKDGen联盟中重复。