He Daijun, Li Chenglong, Yang Chao, Wang Jinwei, Zhao Ming-Hui, Gao Bixia, Zhang Luxia
Department of Nephrology, Peking University First Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China; Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China; Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.
National Institute of Health Data Science at Peking University, Beijing, China.
Atherosclerosis. 2025 Sep;408:120452. doi: 10.1016/j.atherosclerosis.2025.120452. Epub 2025 Jul 17.
Difference between cystatin C and creatinine-based estimated glomerular filtration rate (eGFRdiff) has been suggested to reflect factors that are associated with vascular risk, independent of kidney function. We aimed to prospectively evaluate the association between eGFRdiff and peripheral artery disease (PAD), as well as the potential modifying role of diabetes.
This prospective cohort study included 466,245 participants with concurrent measured serum creatinine and cystatin C and free of PAD at baseline (2006-2010) from the UK Biobank. eGFRdiff was calculated as absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based eGFRs. The incidence of PAD was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with incident PAD. Potential modification by diabetes was examined. The relative importance and the additive value of eGFRdiff in predicting PAD was evaluated.
During a median follow-up of 13.8 years, PAD developed in 7210 participants. Each standard deviation increment of eGFRabdiff was associated with a 33 % lower risk of PAD. For each 10 % increment in eGFRrediff, the hazard ratio (95 % confidence interval) was 0.78 (0.77, 0.80) for PAD. Consistent associations were observed between eGFRdiff and PAD, irrespective of the presence of diabetes. Adding eGFRdiff into the established model could improve the performance of PAD prediction.
eGFRdiff was significantly associated with risk of incident PAD irrespective of the presence of diabetes and provided additional value in predicting PAD.
胱抑素C与基于肌酐的估计肾小球滤过率之间的差异（eGFRdiff）被认为可反映与血管风险相关的因素，且独立于肾功能。我们旨在前瞻性评估eGFRdiff与外周动脉疾病（PAD）之间的关联，以及糖尿病的潜在调节作用。
这项前瞻性队列研究纳入了英国生物银行中466245名在基线时（2006 - 2010年）同时测量了血清肌酐和胱抑素C且无PAD的参与者。eGFRdiff计算为基于胱抑素C的eGFR与基于肌酐的eGFR之间的绝对差值（eGFRabdiff）和比值（eGFRrediff）。使用电子健康记录确定PAD的发病率。采用Cox比例风险回归模型评估eGFRdiff与新发PAD之间的关联。研究了糖尿病的潜在调节作用。评估了eGFRdiff在预测PAD中的相对重要性和附加值。
在中位随访13.8年期间，7210名参与者发生了PAD。eGFRabdiff每增加一个标准差与PAD风险降低33%相关。对于eGFRrediff每增加10%，PAD的风险比（95%置信区间）为0.78（0.77，0.80）。无论是否存在糖尿病，eGFRdiff与PAD之间均观察到一致的关联。将eGFRdiff纳入已建立的模型可提高PAD预测的性能。
无论是否存在糖尿病，eGFRdiff均与新发PAD风险显著相关，并在预测PAD方面提供了额外价值。
