Renal function and risk of dementia: a Mendelian randomization study

The burgeoning recognition of the nexus between renal functionality and the prevalence of dementia has precipitated a surge in research endeavors. This study aims to substantiate the causal relationship between kidney functionality and dementia. We utilized clinical renal function metrics from the Chronic Kidney Disease Genetics (CKDGen) Consortium and diverse dementia types (Alzheimer’s disease [AD] and vascular dementia) from the FinnGen Biobank by using Mendelian randomization analysis. At the stratum of genetic susceptibility, we tested the causal relationship between variations index in renal function and the occurrence of dementia. Inverse-variance weighted (IVW) method was the main analysis, and several supplementary analyses and sensitivity analyses were performed to test the causal estimates. The findings indicate a significant correlation between each unit increase in cystatin C-based estimated glomerular filtration rate (eGFR-cys) levels was significantly associated with a reduction in the incidence of late-onset Alzheimer’s disease (LOAD) (IVW: OR = 0.35, 95% CI: 0.13–0.91, p = 0.031). After adjusting for creatinine-based eGFR (eGFR-cre) and urinary albumin-to-creatinine ratio (UACR), a causal relationship was still identified between elevated levels of eGFR-cys and decreased risk of LOAD (IVW: OR: 0.08; 95% CI: 0.01–0.97, p = 0.047). Sensitivity tests demonstrated the reliability of causal estimates. The association between renal function based on cystatin C and the augmented risk of developing AD lends support to the perspective that regular monitoring of cystatin C may be a valuable investigative biomarker.

肾脏功能与痴呆症发病率之间联系的日益被认识，引发了研究领域的蓬勃发展。本研究旨在证实肾脏功能与痴呆症之间的因果关系。我们通过孟德尔随机化分析，利用慢性肾脏病遗传学（CKDGen）联盟的临床肾脏功能指标和来自FinnGen生物库的多种痴呆类型（阿尔茨海默病[AD]和血管性痴呆）进行了研究。在遗传易感性的层面上，我们检验了肾脏功能变异指数与痴呆症发生之间的因果关系。逆方差加权（IVW）方法是主要分析手段，并进行了多项补充分析和敏感性分析，以检验因果估计的可靠性。研究发现，基于半胱氨酸C的估计肾小球滤过率（eGFR-cys）水平的每单位增加与晚发性阿尔茨海默病（LOAD）发病率的降低存在显著相关性（IVW：比值比=0.35，95%置信区间：0.13–0.91，p=0.031）。在调整了基于肌酐的eGFR（eGFR-cre）和尿微量白蛋白与肌酐比（UACR）之后，eGFR-cys水平的升高与LOAD风险降低之间的因果关系依然存在（IVW：比值比=0.08；95%置信区间：0.01–0.97，p=0.047）。敏感性测试证明了因果估计的可靠性。基于半胱氨酸C的肾脏功能与阿尔茨海默病发展风险增加之间的关联，支持了定期监测半胱氨酸C可能是一个有价值的探索性生物标志物的观点。