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.
Am J Nephrol. 2024;55(1):106-114. doi: 10.1159/000534514. Epub 2023 Oct 9.
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.
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.
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.
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.
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。
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。
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。
在一项 2 队列研究中，uPTM-FetA 与 2 型糖尿病患者的肾功能下降独立相关。该生物标志物与传统危险因素相比具有显著的附加预测能力，表明其可用于 2 型糖尿病患者的肾功能进展。
