尿调蛋白与老年终末期肾病及肾功能下降的相关性：心血管健康研究。
Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study.
机构信息
Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA; Division of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Department of Biostatistics, University of Washington, Seattle, WA.
出版信息
Am J Kidney Dis. 2019 Oct;74(4):501-509. doi: 10.1053/j.ajkd.2019.02.024. Epub 2019 May 22.
RATIONALE & OBJECTIVE: Uromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy.
STUDY DESIGN
Case-cohort study and case-control study.
SETTING & PARTICIPANTS: Random subcohort (n=933) and additional cases of end-stage kidney disease (ESKD) and kidney function decline (≥30% decline in estimated glomerular filtration rate [eGFR]) during follow-up of the Cardiovascular Health Study (CHS).
PREDICTOR
sUMOD level.
OUTCOMES
ESKD (n=14) from the random subcohort and all additional ESKD cases from outside the random subcohort (n=39) during follow-up (10 years, case-cohort study); kidney function decline of≥30% eGFR at 9 years of follow-up in individuals with repeated eGFR assessments from the random subcohort (n=56) and additional cases (n=123). 224 participants from the random subcohort served as controls (case-control study).
ANALYTICAL APPROACH
Modified multivariable Cox regression for ESKD and multivariable logistic regression for kidney function decline. Both analyses adjusted for demographics, eGFR, urinary albumin-creatinine ratio, and other kidney disease progression risk factors.
RESULTS
Mean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127±64ng/mL and eGFR was 63±19mL/min/1.73m. In multivariable analysis, each 1-SD higher sUMOD level was associated with 63% lower risk for ESKD (HR, 0.37; 95% CI, 0.14-0.95). In demographic-adjusted analyses of kidney function decline, each 1-SD higher sUMOD level was associated with 25% lower odds of kidney function decline (OR, 0.75; 95% CI, 0.60-0.95); after multivariable adjustment, the association was attenuated and no longer significant (OR, 0.88; 95% CI, 0.68-1.14).
LIMITATIONS
Possibility of survival bias in the kidney function decline analysis.
CONCLUSIONS
Higher sUMOD levels may identify elderly persons at reduced risk for ESKD.
背景与目的
尿调蛋白由肾小管上皮细胞分泌到血清中，其水平降低与更严重的间质纤维化和肾小管萎缩有关。血清尿调蛋白（sUMOD）水平降低与死亡率和心血管疾病相关。然而，对于 sUMOD 水平与老年人（间质纤维化和肾小管萎缩高发人群）长期肾脏结局之间的关系，我们知之甚少。
研究设计
病例-队列研究和病例对照研究。
研究地点和参与者
心血管健康研究（CHS）中随机亚组（n=933）和随访期间（10 年，病例-队列研究）终末期肾病（ESKD）和肾功能下降（估计肾小球滤过率[eGFR]下降≥30%）的额外病例；在随机亚组中具有重复 eGFR 评估的个体（n=56）和额外病例（n=123）中，9 年随访时 eGFR 下降≥30%。随机亚组的 224 名参与者作为对照（病例对照研究）。
预测因子
sUMOD 水平。
结局
随机亚组中的 ESKD（n=14）和随机亚组以外的所有其他 ESKD 病例（n=39）（随访；10 年，病例-队列研究）；在随机亚组中具有重复 eGFR 评估的个体（n=56）和额外病例（n=123）中，9 年随访时 eGFR 下降≥30%（病例对照研究）。
分析方法
用于 ESKD 的改良多变量 Cox 回归和用于肾功能下降的多变量逻辑回归。这两种分析均调整了人口统计学、eGFR、尿白蛋白/肌酐比值和其他肾脏疾病进展风险因素。
结果
随机亚组的平均年龄为 78 岁，40%为男性，15%为黑人。sUMOD 水平的平均值为 127±64ng/mL，eGFR 为 63±19mL/min/1.73m。在多变量分析中，sUMOD 水平每增加 1 个标准差，ESKD 的风险降低 63%（HR，0.37；95%CI，0.14-0.95）。在肾功能下降的人口统计学调整分析中，sUMOD 水平每增加 1 个标准差，肾功能下降的几率降低 25%（OR，0.75；95%CI，0.60-0.95）；经过多变量调整后，这种关联减弱且不再显著（OR，0.88；95%CI，0.68-1.14）。
局限性
肾功能下降分析中可能存在生存偏倚。
结论
较高的 sUMOD 水平可能表明老年人患 ESKD 的风险降低。
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