Semnani-Azad Zhila, Wang Windy Z N, Cole David E C, Johnston Luke W, Wong Betty Y L, Fu Lei, Retnakaran Ravi, Harris Stewart B, Hanley Anthony J
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada.
J Endocr Soc. 2024 Jan 31;8(3):bvae014. doi: 10.1210/jendso/bvae014. eCollection 2024 Jan 16.
Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined.
Our objective was to assess the association of uVDBP with longitudinal changes in kidney function.
Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727). Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used as measures of kidney function. Measurements of uVDBP were performed with enzyme-linked immunosorbent assay and normalized to urine creatinine (uVDBP:cr). Generalized estimating equations (GEEs) evaluated longitudinal associations of uVDBP and uVDBP:cr with measures of kidney function, adjusting for covariates.
Renal uVDBP loss increased with ACR severity at baseline. Individuals with normoalbuminuria, microalbuminuria, and macroalbuminuria had median log uVDBP:cr concentrations of 1.62 μg/mmol, 2.63 μg/mmol, and 2.48 μg/mmol, respectively, and ACR positively correlated with uVDBP concentrations ( = 0.37; < .001). There was no significant association between uVDBP and eGFR at baseline. Adjusted longitudinal GEE models indicated that each SD increase both in baseline and longitudinal uVDBP:cr was significantly associated with higher ACR over 6 years (β = 30.67 and β = 32.91, respectively). Conversely, neither baseline nor longitudinal uVDBP:cr measures showed a significant association with changes in eGFR over time. These results suggest that loss of uVDBP:cr over time may be a useful marker for predicting renal tubular damage in individuals at risk for diabetes.
近期研究报告称，糖尿病肾病患者的尿维生素D结合蛋白（uVDBP）浓度升高，尽管尚未研究uVDBP预测肾功能随时间恶化的效用。
我们的目的是评估uVDBP与肾功能纵向变化之间的关联。
来自前瞻性代谢和胰岛细胞评估（PROMISE）研究的有2型糖尿病风险的成年人在6年内进行了3次评估（n = 727）。尿白蛋白与肌酐比值（ACR）和估计肾小球滤过率（eGFR）用作肾功能指标。采用酶联免疫吸附测定法测量uVDBP，并将其标准化为尿肌酐（uVDBP:cr）。广义估计方程（GEE）评估uVDBP和uVDBP:cr与肾功能指标的纵向关联，并对协变量进行调整。
基线时，肾脏uVDBP丢失随ACR严重程度增加。正常白蛋白尿、微量白蛋白尿和大量白蛋白尿患者的uVDBP:cr中位数浓度分别为1.62μg/mmol、2.63μg/mmol和2.48μg/mmol，且ACR与uVDBP浓度呈正相关（ = 0.37； <.001）。基线时uVDBP与eGFR之间无显著关联。调整后的纵向GEE模型表明，基线和纵向uVDBP:cr每增加1个标准差，在6年内均与较高的ACR显著相关（β分别为30.67和32.91）。相反，基线和纵向uVDBP:cr测量值均未显示与eGFR随时间的变化有显著关联。这些结果表明，随着时间推移uVDBP:cr的丢失可能是预测糖尿病风险个体肾小管损伤的有用标志物。
