Cao Can, Zhang Jiale, Ma Tong, Miao Juan, Sun Weiwei
Department of Nephrology and Endocrinology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Front Endocrinol (Lausanne). 2025 May 21;16:1557813. doi: 10.3389/fendo.2025.1557813. eCollection 2025.
Diabetic kidney disease (DKD) represents a leading complication of diabetes, frequently progressing to end-stage renal disease (ESRD), which significantly impairs patients' quality of life and imposes substantial healthcare burdens. Consequently, early detection and intervention in DKD are paramount. The incorporation of surrogate endpoints in clinical trials has emerged as a pivotal strategy for assessing the efficacy of novel therapies, facilitating the reduction of trial duration and associated costs. Currently, the rate of change in estimated glomerular filtration rate (eGFR) and urinary albumin excretion, either independently or in combination, serve as reliable surrogate endpoints for evaluating DKD progression. Although novel biomarkers such as KIM-1 and TNFR2 are not yet recommended as standalone surrogate endpoints for DKD, they hold potential when used in combination with established markers, such as eGFR slope and urinary albumin change rate, to improve the prediction of ESRD risk. While omics-based indicators demonstrate promise in DKD research, their utility requires further validation, particularly through long-term follow-up and dynamic monitoring, to establish their effectiveness and clinical applicability. Future research should prioritize the validation and optimization of potential surrogate endpoints through long-term follow-up studies and large-scale cohorts.
糖尿病肾病（DKD）是糖尿病的主要并发症，常进展为终末期肾病（ESRD），这严重损害患者的生活质量并带来巨大的医疗负担。因此，DKD的早期检测和干预至关重要。在临床试验中纳入替代终点已成为评估新疗法疗效的关键策略，有助于缩短试验持续时间和降低相关成本。目前，估计肾小球滤过率（eGFR）和尿白蛋白排泄的变化率，单独或联合使用，是评估DKD进展的可靠替代终点。尽管新型生物标志物如KIM-1和TNFR2尚未被推荐作为DKD的独立替代终点，但它们与既定标志物（如eGFR斜率和尿白蛋白变化率）联合使用时，在改善ESRD风险预测方面具有潜力。虽然基于组学的指标在DKD研究中显示出前景，但其效用需要进一步验证，特别是通过长期随访和动态监测，以确定其有效性和临床适用性。未来的研究应通过长期随访研究和大规模队列优先验证和优化潜在的替代终点。
