Lee Chi-Ho, Lui David Tak-Wai, Cheung Chloe Yu-Yan, Fong Carol Ho-Yi, Yuen Michele Mae-Ann, Chow Wing-Sun, Xu Aimin, Lam Karen Siu-Ling
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong.
Nephrol Dial Transplant. 2023 Feb 28;40(4):788-96. doi: 10.1093/ndt/gfad034.
Thrombospondin-2 (TSP2) is a matricellular protein with tissue expression induced by hyperglycaemia. TSP2 has been implicated in non-diabetic renal injury in preclinical studies and high circulating levels were associated with worse kidney function in cross-sectional clinical studies. Therefore, we investigated the prospective associations of circulating TSP2 level with kidney function decline and the trajectories of estimated glomerular filtration rate (eGFR) in type 2 diabetes.
Baseline serum TSP2 level was measured in 5471 patients with type 2 diabetes to evaluate its association with incident eGFR decline, defined as ≥ 40% sustained eGFR decline, using multivariable Cox regression analysis. Among participants with relatively preserved kidney function (Baseline eGFR ≥ 60 ml/min/1.73m2), joint latent class modelling was employed to identify three different eGFR trajectories. Their associations with baseline serum TSP2 was evaluated using multinomial logistic regression analysis. The predictive performance of serum TSP2 level was examined using time-dependent c-statistics and calibration statistics.
Over a median follow-up of 8.8 years, 1083 patients (19.8%) developed eGFR decline. Baseline serum TSP2 level was independently associated with incident eGFR decline (HR 1.21, 95%CI 1.07-1.37, P = 0.002). With internal validation, incorporating serum TSP2 to a model of clinical risk factors including albuminuria led to significant improvement in c-statistics from 83.9 to 84.4 (P < 0.001). Among patients with eGFR ≥ 60 ml/min/1.73m2, baseline serum TSP2 level was independently associated with a rapidly declining eGFR trajectory (HR 1.63, 95%CI 1.26-2.10, P < 0.001).
Serum TSP2 level was independently associated with incident eGFR decline, particularly a rapidly declining trajectory, in type 2 diabetes.
血小板反应蛋白-2（TSP2）是一种基质细胞蛋白，其组织表达受高血糖诱导。在临床前研究中，TSP2与非糖尿病性肾损伤有关，在横断面临床研究中，循环水平升高与肾功能较差有关。因此，我们研究了2型糖尿病患者循环TSP2水平与肾功能下降以及估计肾小球滤过率（eGFR）轨迹的前瞻性关联。
对5471例2型糖尿病患者测定基线血清TSP2水平，采用多变量Cox回归分析评估其与eGFR下降事件的关联，eGFR下降定义为持续eGFR下降≥40%。在肾功能相对保留的参与者（基线eGFR≥60 ml/min/1.73m2）中，采用联合潜在类别模型识别三种不同的eGFR轨迹。使用多项逻辑回归分析评估它们与基线血清TSP2的关联。使用时间依赖性c统计量和校准统计量检验血清TSP2水平的预测性能。
在中位随访8.8年期间，1083例患者（19.8%）出现eGFR下降。基线血清TSP2水平与eGFR下降事件独立相关（HR 1.21，95%CI 1.07-1.37，P = 0.002）。经内部验证，将血清TSP2纳入包括蛋白尿在内的临床危险因素模型后，c统计量从83.9显著提高到84.4（P < 0.001）。在eGFR≥60 ml/min/...展开全部
