Retinal structural and vascular alterations in diabetic kidney disease: A bidirectional Mendelian randomization study

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research Pub Date : 2026-07-01 Epub Date: 2026-03-03 DOI:10.1016/j.mvr.2026.104928

Shulei Man , Kefan Mou , Yifan Zhang , Yuzhu Gao , Xue Wu , Hanyue Xu , Ming Zhang

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引用次数: 0

Abstract

Purpose

Growing evidence indicates retinal thickness and microvascular changes have been associated with diabetic kidney disease (DKD). Nevertheless, the causal links between them have yet to be fully elucidated. We utilized Mendelian randomization (MR) to investigate the bidirectional causal relationship between DKD and retinal structural and vascular alterations.

Methods

The bidirectional two-sample MR was conducted using genome-wide association studies (GWAS) summary statistics from European populations. Eight DKD-related phenotypes were investigated in relation to retinal layer thickness and microvascular traits.

Results

The forward MR revealed that macroalbuminuria was associated with increased inner nuclear layer (INL) thickness (OR 1.006 [95% CI 1.000–1.012], P = 0.040), and the combined phenotype of chronic kidney disease and diabetic kidney disease (CKD-DN) was linked to greater choroidal thickness (OR 1.005 [95% CI 1.000–1.009], P = 0.047). All DKD showed negative associations with retinal vascular density (RVD) (OR 0.979 [95% CI 0.965–0.993], P = 0.003) and retinal vascular fractal dimension (RVFD) (OR 0.980 [95% CI 0.966–0.993], P = 0.004). In reverse MR, increased INL thickness predicted higher risk of end-stage renal disease (ESRD) (OR 1.444 [95% CI 1.110–1.878], P = 0.006) and extreme chronic kidney disease (CKD) (OR 1.322 [95% CI 1.026–1.704], P = 0.031). Thickening of outer retinal layers was associated with CKD (OR 1.144 [95% CI 1.020–1.284], P = 0.021).

Conclusions

These findings highlight a potential bidirectional causal link between renal dysfunction and retinal neurovascular changes. Retinal imaging biomarkers may serve as noninvasive indicators of DKD risk and progression, warranting further validation.

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糖尿病肾病视网膜结构和血管改变：一项双向孟德尔随机研究

目的：越来越多的证据表明视网膜厚度和微血管变化与糖尿病肾病（DKD）有关。然而，它们之间的因果关系尚未得到充分阐明。我们使用孟德尔随机化（MR）来研究DKD与视网膜结构和血管改变之间的双向因果关系。方法：利用欧洲人群的全基因组关联研究（GWAS）汇总统计数据进行双向双样本MR。研究了8种dkd相关表型与视网膜层厚度和微血管性状的关系。结果：前向MR显示，大量蛋白尿与内核层（INL）厚度增加有关（OR 1.006 [95% CI 1.000-1.012], P = 0.040），慢性肾病和糖尿病肾病（CKD-DN）联合表型与脉络膜厚度增加有关（OR 1.005 [95% CI 1.000-1.009], P = 0.047）。DKD与视网膜血管密度（RVD）（OR 0.979 [95% CI 0.965 ~ 0.993], P = 0.003）、视网膜血管分形维数（RVFD）（OR 0.980 [95% CI 0.966 ~ 0.993], P = 0.004）呈负相关。在反向MR中，INL厚度增加预示着终末期肾病（ESRD）（OR 1.444 [95% CI 1.110-1.878], P = 0.006）和极端慢性肾病（CKD）（OR 1.322 [95% CI 1.026-1.704], P = 0.031）的风险增加。视网膜外层增厚与CKD相关（OR 1.144 [95% CI 1.020-1.284], P = 0.021）。结论：这些发现强调了肾功能障碍和视网膜神经血管改变之间潜在的双向因果关系。视网膜成像生物标志物可以作为DKD风险和进展的非侵入性指标，需要进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microvascular research 医学-外周血管病

CiteScore

6.00

自引率

3.20%

发文量

158

审稿时长

43 days

期刊介绍： Microvascular Research is dedicated to the dissemination of fundamental information related to the microvascular field. Full-length articles presenting the results of original research and brief communications are featured. Research Areas include: • Angiogenesis • Biochemistry • Bioengineering • Biomathematics • Biophysics • Cancer • Circulatory homeostasis • Comparative physiology • Drug delivery • Neuropharmacology • Microvascular pathology • Rheology • Tissue Engineering.