Zeng Xiaomin, Hu Yijun, Chen Yuanhan, Lin Zhanjie, Liang Yingying, Liu Baoyi, Zhong Pingting, Xiao Yu, Li Cong, Wu Guanrong, Kong Huiqian, Du Zijing, Ren Yun, Fang Ying, Ye Zhiming, Yang Xiaohong, Yu Honghua
Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Front Neurosci. 2021 Nov 18;15:703898. doi: 10.3389/fnins.2021.703898. eCollection 2021.
Widespread neural and microvascular injuries are common in chronic kidney disease (CKD), increasing risks of neurovascular complications and mortality. Early detection of such changes helps assess the risks of neurovascular complications for CKD patients. As an extension of central nervous system, the retina provides a characteristic window to observe neurovascular alterations in CKD. This study aimed to determine the presence of retinal neurovascular impairment in different stages of CKD. One hundred fifteen non-diabetic and non-dialytic CKD patients of all stages and a control group of 35 healthy subjects were included. Retinal neural and microvascular parameters were obtained by optical coherence tomography angiography (OCTA) examination. CKD 1-2 group (versus control group) had greater odds of having decreased retinal ganglion cell-inner plexiform layer thickness (GC-IPLt) (odds ratio [OR]: 0.92; 95% confidence interval [CI]: 0.86-0.98), increased ganglion cell complex-focal loss volume (GCC-FLV) (OR: 3.51; 95% CI: 1.27-9.67), and GCC-global loss volume (GCC-GLV) (OR: 2.48; 95% CI: 1.27-4.82). The presence of advanced stages of CKD (CKD 3-5 group versus CKD 1-2 group) had greater odds of having decreased retinal vessel density in superficial vascular plexus (SVP)-WholeImage (OR: 0.77, 95% CI: 0.63-0.92), SVP-ParaFovea (OR: 0.83, 95% CI: 0.71-0.97), SVP-ParaFovea (OR: 0.76, 95% CI: 0.63-0.91), deep vascular plexus (DVP)-WholeImage (OR: 0.89, 95% CI: 0.81-0.98), DVP-ParaFovea (OR: 0.88, 95% CI: 0.78-0.99), and DVP-PeriFovea (OR: 0.90, 95% CI: 0.83-0.98). Besides, stepwise multivariate linear regression among CKD patients showed that β2-microglobulin was negatively associated with GC-IPLt (β: -0.294; 95% CI: -0.469 ∼ -0.118), and parathyroid hormone was positively associated with increased GCC-FLV (β: 0.004; 95% CI: 0.002∼0.006) and GCC-GLV (β: 0.007; 95% CI: 0.004∼0.01). Urine protein to creatinine ratio was positively associated with increased GCC-FLV (β: 0.003; 95% CI: 0.001∼0.004) and GCC-GLV (β: 0.003; 95% CI: 0.001∼0.006). Retinal neuronal impairment is present in early stages of CKD (stages 1-2), and it is associated with accumulation of uremic toxins and higher UACR, while retinal microvascular hypoperfusion, which is associated with worse eGFR, was only observed in relatively advanced stages of CKD (stages 3-5). The results highlight the importance of monitoring retinal neurovascular impairment in different stages of CKD.
广泛的神经和微血管损伤在慢性肾脏病（CKD）中很常见，会增加神经血管并发症和死亡风险。早期发现这些变化有助于评估CKD患者发生神经血管并发症的风险。视网膜作为中枢神经系统的延伸，为观察CKD中的神经血管改变提供了一个独特的窗口。本研究旨在确定CKD不同阶段视网膜神经血管损伤的存在情况。纳入了115例各阶段的非糖尿病、非透析CKD患者以及35名健康受试者作为对照组。通过光学相干断层扫描血管造影（OCTA）检查获取视网膜神经和微血管参数。CKD 1-2组（与对照组相比）视网膜神经节细胞-内丛状层厚度（GC-IPLt）降低的几率更高（优势比[OR]：0.92；95%置信区间[CI]：0.86-0.98），神经节细胞复合体-局灶性损失体积（GCC-FLV）增加（OR：3.51；95%CI：1.27-9.67），以及GCC-整体损失体积（GCC-GLV）增加（OR：2.48；95%CI：1.27-4.82）。CKD晚期阶段（CKD 3-5组与CKD 1-2组相比），浅层血管丛（SVP）-全图像、SVP-黄斑旁、SVP-黄斑周、深层血管丛（DVP）-全图像、DVP-黄斑旁和DVP-黄斑周的视网膜血管密度降低的几率更高。此外，CKD患者的逐步多元线性回归显示，β2-微球蛋白与GC-IPLt呈负相关（β：-0.294；95%CI：-0.469～-0.118），甲状旁腺激素与GCC-FLV增加（β：0.004；95%CI：0.002～0.006）和GCC-GLV增加（β：0.007；95%CI：0.004～0.01）呈正相关。尿蛋白与肌酐比值与GCC-FLV增加（β：0.003；95%CI：0.001～0.004）和GCC-GLV增加（β：0.003；95%CI：0.001～0.006）呈正相关。视网膜神经元损伤存在于CKD早期阶段（1-2期），且与尿毒症毒素蓄积和更高的尿白蛋白肌酐比值相关，而与估算肾小球滤过率降低相关的视网膜微血管灌注不足仅在CKD相对晚期阶段（3-5期）观察到。结果强调了监测CKD不同阶段视网膜神经血管损伤的重要性。
