Kidney Health Research Collaborative, University of California, San Francisco and San Francisco Veterans Affairs Health Care System, San Francisco, California, USA.
Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, USA.
Am J Hypertens. 2022 Dec 8;35(12):1006-1013. doi: 10.1093/ajh/hpac102.
Urine biomarkers of kidney tubule health may distinguish aspects of kidney damage that cannot be captured by current glomerular measures. Associations of clinical risk factors with specific kidney tubule biomarkers have not been evaluated in detail.
We performed a cross-sectional study in the Systolic Blood Pressure Intervention Trial among 2,436 participants with a baseline estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Associations between demographic and clinical characteristics with urine biomarkers of kidney tubule health were evaluated using simultaneous multivariable linear regression of selected variables.
Each standard deviation higher age (9 years) was associated with 13% higher levels of chitinase-3-like protein-1 (YKL-40), indicating higher levels of tubulointerstitial inflammation and repair. Men had 31% higher levels of alpha-1 microglobulin and 16% higher levels of beta-2 microglobulin, reflecting worse tubule resorptive function. Black race was associated with significantly higher levels of neutrophil gelatinase-associated lipocalin (12%) and lower kidney injury molecule-1 (26%) and uromodulin (22%). Each standard deviation (SD) higher systolic blood pressure (SBP) (16 mmHg) was associated with 10% higher beta-2 microglobulin and 10% higher alpha-1 microglobulin, reflecting lower tubule resorptive function.
Clinical and demographic characteristics, such as race, sex, and elevated SBP, are associated with unique profiles of tubular damage, which could reflect under-recognized patterns of kidney tubule disease among persons with decreased eGFR.
尿液肾小管健康生物标志物可以区分当前肾小球测量无法捕捉到的肾损伤方面。尚未详细评估临床危险因素与特定肾小管生物标志物之间的关联。
我们在基线估算肾小球滤过率（eGFR）<60 ml/min/1.73 m2 的收缩压干预试验中进行了一项横断面研究。使用选定变量的同时多变量线性回归评估了人口统计学和临床特征与肾小管健康的尿液生物标志物之间的关联。
年龄（9 岁）每增加一个标准差，壳聚糖酶-3 样蛋白-1（YKL-40）的水平就会升高 13%，表明肾小管间质炎症和修复水平较高。男性的α-1 微球蛋白水平升高 31%，β-2 微球蛋白水平升高 16%，反映出肾小管重吸收功能下降。黑种人种族与中性粒细胞明胶酶相关脂质运载蛋白（12%）水平显著升高和肾损伤分子-1（26%）和尿调蛋白（22%）水平降低有关。收缩压（SBP）每增加一个标准差（SD）（16mmHg），β-2 微球蛋白和α-1 微球蛋白的水平就会升高 10%，反映出肾小管重吸收功能下降。
临床和人口统计学特征，如种族、性别和升高的 SBP，与肾小管损伤的独特特征有关，这可能反映了 eGFR 降低的人群中肾小管疾病的潜在模式。
