Background

Estimated glomerular filtration rate (eGFR), albuminuria and serum uric acid (SUA) are markers of kidney function that have been associated with cognitive ability. However, whether these associations are causal is unclear.

Methods

We performed one-sample Mendelian randomization (MR) to estimate the effects of kidney function markers on cognitive performance using data from the UK Biobank. Polygenic scores for SUA, urine albumin to creatinine ratio (ACR), estimated glomerular filtration rate based on serum creatinine (eGFRcre) and serum cystatin C (eGFRcys) were used as instrumental variables, and cognitive function outcomes included tests of verbal-numeric reasoning, reaction time, visual memory, and numeric memory.

Results

We found no evidence of a causal effect of genetically determined SUA, eGFRcre or eGFRcys on cognitive function outcomes. There was no association between a polygenic score for ACR and verbal-numeric reasoning or numeric memory. However, there was suggestive evidence of a relationship between genetically increased ACR and slower reaction time and worse visual memory. ACR was no longer significantly associated with visual memory in analyses using an unweighted polygenic score and in analyses stratified by sex and age category. Pleiotropy adjusted estimates were directionally consistent with those of the principal analysis but overlapped with the null.

Conclusions

This MR study does not support causal effects of SUA, eGFRcre or eGFRcys on cognitive performance. Genetically increased ACR was associated with slower processing speed and visual memory, but results need confirmation in independent samples.

中文翻译：

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肾功能和认知能力的生物标志物：孟德尔随机研究

背景

估计肾小球滤过率 (eGFR)、白蛋白尿和血清尿酸 (SUA) 是与认知能力相关的肾功能标志物。然而，这些关联是否存在因果关系尚不清楚。

方法

我们使用英国生物银行的数据进行单样本孟德尔随机化 (MR)，以估计肾功能标记物对认知能力的影响。SUA 的多基因评分、尿白蛋白与肌酐比值 (ACR)、基于血清肌酐 (eGFRcre) 和血清胱抑素 C (eGFRcys) 的估计肾小球滤过率用作工具变量，认知功能结果包括语言-数字推理测试、反应时间、视觉记忆和数字记忆。

结果

我们没有发现任何证据表明基因决定的 SUA、eGFRcre 或 eGFRcys 对认知功能结果有因果影响。ACR 多基因评分与言语数字推理或数字记忆之间没有关联。然而，有暗示性证据表明，遗传性 ACR 增加与反应速度减慢和视觉记忆能力较差之间存在关系。在使用未加权多基因评分的分析以及按性别和年龄类别分层的分析中，ACR 不再与视觉记忆显着相关。多效性调整估计值与主要分析的方向一致，但与零值重叠。

结论

这项 MR 研究不支持 SUA、eGFRcre 或 eGFRcys 对认知表现的因果影响。基因增加的 ACR 与较慢的处理速度和视觉记忆有关，但结果需要在独立样本中进行确认。