Kidney Health Research Collaborative and Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California; San Francisco VA Health Care System, San Francisco, California; Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Kidney Health Research Collaborative and Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California; San Francisco VA Health Care System, San Francisco, California.
Am J Kidney Dis. 2024 Jan;83(1):71-78. doi: 10.1053/j.ajkd.2023.05.017. Epub 2023 Sep 9.
RATIONALE & OBJECTIVE: Uromodulin (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.
Prospective cohort.
SETTING & PARTICIPANTS: Participants 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.
Baseline log-transformed UMOD and change in UMOD over 2 years.
KFRT and mortality.
Cox proportional hazards and mixed-effects models.
Among 500 participants with baseline serum UMOD levels (mean age, 54y; 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).
Small sample size and limited generalizability.
Lower 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 SUMMARY: Prior 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.
尿调蛋白（UMOD）是尿液中含量最丰富的蛋白质，已成为肾小管健康的有前途的生物标志物。循环 UMOD 也可检测到，但水平较低。我们评估了血清 UMOD 水平是否与接受替代治疗的新发肾衰竭（KFRT）风险和死亡率相关。
前瞻性队列研究。
在 AASK（非洲裔美国人肾脏病和高血压研究）中，有可用的储存血清样本，来自生物标志物测量的 0、12 和 24 个月访视。
基线对数转换的 UMOD 和 2 年内 UMOD 的变化。
KFRT 和死亡率。
Cox 比例风险和混合效应模型。
在 500 名基线血清 UMOD 水平的参与者中（平均年龄 54 岁；37%为女性），中位时间为 8.5 年期间发生了 161 例 KFRT 事件。在调整基线人口统计学因素、临床因素、肾小球滤过率、尿蛋白-肌酐比的对数转换以及随机治疗组后，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）。对于年度 UMOD 变化，每个标准差的降低与 KFRT 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。与培哚普利相比，美托洛尔（P<0.001）以及与标准血压目标相比，强化血压目标（P=0.002）的 UMOD 水平下降更为陡峭。
样本量小且推广性有限。
在患有高血压和慢性肾脏病的非裔美国成年人队列中，基线 UMOD 水平较低，随时间推移 UMOD 水平下降更为陡峭，与随后发生 KFRT 的风险较高相关。
先前对尿液中最丰富的蛋白质尿调蛋白（UMOD）和肾脏疾病的研究主要集中在尿液 UMOD 水平上。本研究评估了血清 UMOD 水平与高血压和慢性肾脏病的非裔美国成年人队列中接受替代治疗的肾衰竭（KFRT）风险和死亡率的相关性。研究发现，即使考虑了基线肾脏指标，基线 UMOD 水平较低的参与者更有可能经历 KFRT。同样，UMOD 年度下降幅度较大的参与者也有更高的肾衰竭风险。基线和年度 UMOD 变化均与死亡率无关。血清 UMOD 是肾脏健康的有前途的生物标志物。
