Associations of Baseline and Longitudinal Serum Uromodulin With Kidney Failure and Mortality: Results From the African American Study of Kidney Disease and Hypertension (AASK) Trial.
Associations of Baseline and Longitudinal Serum Uromodulin With Kidney Failure and Mortality: Results From the African American Study of Kidney Disease and Hypertension (AASK) Trial.
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基线和纵向血清尿调节蛋白与肾衰竭和死亡率的关联：非裔美国人肾脏疾病和高血压研究 (AASK) 试验的结果。
DOI：
10.1053/j.ajkd.2023.05.017
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Grams,MorganE
中科院分区：
文献类型：
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作者：
Chen,TeresaK;Estrella,MichelleM;Appel,LawrenceJ;Surapaneni,AdityaL;Köttgen,Anna;Obeid,Wassim;Parikh,ChiragR;Grams,MorganE
原理与目的尿调蛋白(UMOD)是尿液中含量最丰富的蛋白质，是一种很有前途的肾小管健康标志物。循环中的UMOD也可以检测到，但水平较低。我们评估了血清UMOD水平是否与使用替代疗法(KFRT)发生肾功能衰竭的风险和死亡率相关。研究设计前瞻性队列。设置和参与者AASK(非裔美国人肾脏疾病和高血压研究)的参与者使用来自0、12和24个月就诊的可用储存血清样本进行生物标记物测量。预测因素基线对数转换的UMOD和UMOD的变化超过2年。结果KFRT和死亡率。分析方法比例风险和混合效应模型。结果在500名血清UMOD水平基线(平均年龄54岁；女性为37%)的参与者中，KFRT事件发生在中位8.5年。在调整了基线人口学因素、临床因素、肾小球滤过率、对数转化尿蛋白/肌酐比率和随机治疗组后，基线UMOD水平降低50%与KFRT风险增加35%独立相关(调整后的HR，1.35；95%CI，1.07-1.70)。对于每年UMOD的变化，每1个标准差的变化与KFRT的风险增加67%相关(调整后的HR，1.67；95%CI，1.41-1.99)。基线UMOD和UMOD变化与死亡率无关。美托洛尔与雷米普利相比(P<；0.001)以及强化血压目标与标准血压目标(P=0.002)相比，UMOD水平下降幅度更大(P=0.002)。限制样本量小，推广有限。结论：在一组患有慢性肾脏疾病和高血压的非裔美国成年人中，UMOD水平较低，且随时间推移UMOD下降幅度较大，与随后发生KFRT的风险较高相关。在一组患有高血压和慢性肾脏疾病的非裔美国成年人中，本研究评估了血清UMOD水平与替代疗法(KFRT)肾衰竭风险和死亡率的关系。研究发现，即使考虑了基线肾脏指标，UMOD水平较低的参与者也更有可能经历KFRT。同样，经历了UMOD年下降幅度更大的参与者也有更高的肾衰竭风险。UMOD的基线和年度变化均与死亡率无关。血清UMOD是一种很有前景的肾脏健康生物标志物。
Rationale & ObjectiveUromodulin (UMOD) is the most abundant protein found in urine and has emerged as a promising biomarker of tubule health. Circulating UMOD is also detectable, but at lower levels. We evaluated whether serum UMOD levels were associated with the risks of incident kidney failure with replacement therapy (KFRT) and mortality.Study DesignProspective cohort.Setting & ParticipantsParticipants in AASK (the African American Study of Kidney Disease and Hypertension) with available stored serum samples from the 0-, 12-, and 24-month visits for biomarker measurement.PredictorsBaseline log-transformed UMOD and change in UMOD over 2 years.OutcomesKFRT and mortality.Analytical ApproachCox proportional hazards and mixed-effects models.ResultsAmong 500 participants with baseline serum UMOD levels (mean age, 54 y; 37% female), 161 KFRT events occurred during a median of 8.5 years. After adjusting for baseline demographic factors, clinical factors, glomerular filtration rate, log-transformed urine protein-creatinine ratio, and randomized treatment groups, a 50% lower baseline UMOD level was independently associated with a 35% higher risk of KFRT (adjusted HR, 1.35; 95% CI, 1.07-1.70). For annual UMOD change, each 1–standard deviation lower change was associated with a 67% higher risk of KFRT (adjusted HR, 1.67; 95% CI, 1.41-1.99). Baseline UMOD and UMOD change were not associated with mortality. UMOD levels declined more steeply for metoprolol versus ramipril (P< 0.001) as well as for intensive versus standard blood pressure goals (P= 0.002).LimitationsSmall sample size and limited generalizability.ConclusionsLower UMOD levels at baseline and steeper declines in UMOD over time were associated with a higher risk of subsequent KFRT in a cohort of African American adults with chronic kidney disease and hypertension.Plain-Language SummaryPrior studies of uromodulin (UMOD), the most abundant protein in urine, and kidney disease have focused primarily on urinary UMOD levels. The present study evaluated associations of serum UMOD levels with the risks of kidney failure with replacement therapy (KFRT) and mortality in a cohort of African American adults with hypertension and chronic kidney disease. It found that participants with lower levels of UMOD at baseline were more likely to experience KFRT even after accounting for baseline kidney measures. Similarly, participants who experienced steeper annual declines in UMOD also had a heightened risk of kidney failure. Neither baseline nor annual change in UMOD was associated with mortality. Serum UMOD is a promising biomarker of kidney health.