尿胎球蛋白 A 片段可预测两种不同种族 2 型糖尿病队列中估算肾小球滤过率的进行性下降。

Urinary Fetuin-A Fragments Predict Progressive Estimated Glomerular Filtration Rate Decline in Two Independent Type 2 Diabetes Cohorts of Different Ethnicities.

机构信息

Department of Pediatrics, Division of Nephrology, National Taiwan University Hospital, Taipei, Taiwan,

Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

出版信息

Am J Nephrol. 2024;55(1):106-114. doi: 10.1159/000534514. Epub 2023 Oct 9.

DOI:10.1159/000534514

Abstract

INTRODUCTION

There is a great clinical need for novel markers to predict kidney function decline in patients with type 2 diabetes. We explored the potential of posttranslationally modified fetuin-A fragments in urine (uPTM-FetA) as such a marker.

METHODS

We included patients with type 2 diabetes from two independent, nonoverlapping prospective cohort studies. A cut-off for uPTM-FetA, measured via ELISA method, was determined using the Youden index in the primary cohort of patients with type 2 diabetes from Taiwan. Kidney endpoint was defined as an estimated glomerular filtration rate (eGFR) decline ≥30% from baseline, reaching of an eGFR <15 mL/min/1.73 m2, or a need of renal replacement therapy. Prospective associations were assessed in Cox regression models. All analyses were replicated in a cohort of patients with type 2 diabetes from the Netherlands.

RESULTS

In total, 294 patients with type 2 diabetes (age 61 ± 10 years, 55% male, eGFR 88 ± 16 mL/min/1.73 m2) were included in the primary cohort. During a follow-up of median 4.6 years, 42 participants (14%) experienced the kidney endpoint. Using the defined cut-off, a high uPTM-FetA was associated with a higher risk of renal function decline (Plog-rank < 0.0001). This association was similar in subgroups depending on albuminuria. This association remained, independent of age, sex, baseline eGFR, albuminuria, HbA1c, and other potential confounders (HR: 9.94; 95% CI: 2.96-33.40; p < 0.001 in the final model). Analyses in the validation cohort (376 patients with type 2 diabetes, age 64 ± 11 years, 66% male, eGFR 76 ± 24 mL/min/1.73 m2) using the same cut-off yielded similar results.

CONCLUSION

uPTM-FetA was independently associated with kidney function decline in patients with type 2 diabetes validated in a 2-cohort study. The significant additive predictive power of this biomarker from conventional risk factors suggests its clinical use for renal function progression in patients with type 2 diabetes.

摘要

简介

临床上急需新的标志物来预测 2 型糖尿病患者的肾功能下降。我们探讨了尿液中翻译后修饰的胎球蛋白-A 片段（uPTM-FetA）作为此类标志物的潜力。

方法

我们纳入了来自两个独立、无重叠的前瞻性队列研究的 2 型糖尿病患者。在台湾的 2 型糖尿病患者的主要队列中，使用 ELISA 方法测量 uPTM-FetA 的截断值，通过 Youden 指数确定。肾脏终点定义为 eGFR 较基线下降≥30%，达到 eGFR <15 mL/min/1.73 m2，或需要肾脏替代治疗。在 Cox 回归模型中评估前瞻性关联。所有分析均在来自荷兰的 2 型糖尿病患者队列中进行了复制。

结果

总共纳入了 294 例 2 型糖尿病患者（年龄 61 ± 10 岁，55%为男性，eGFR 88 ± 16 mL/min/1.73 m2）。在中位随访 4.6 年期间，42 名患者（14%）出现了肾脏终点。使用定义的截断值，uPTM-FetA 较高与肾功能下降的风险较高相关（对数秩检验 <0.0001）。这种关联在根据白蛋白尿的亚组中是相似的。这种关联仍然存在，独立于年龄、性别、基线 eGFR、白蛋白尿、HbA1c 和其他潜在的混杂因素（最终模型中的 HR：9.94；95%CI：2.96-33.40；p <0.001）。在使用相同截断值的验证队列（376 例 2 型糖尿病患者，年龄 64 ± 11 岁，66%为男性，eGFR 76 ± 24 mL/min/1.73 m2）中进行的分析得出了类似的结果。