Carlsson Axel C, Larsson Anders, Helmersson-Karlqvist Johanna, Lind Lars, Ingelsson Erik, Larsson Tobias E, Bottai Matteo, Sundström Johan, Ärnlöv Johan
Centre for Family Medicine, Department of Neurobiology, Care Sciences, and Society, Karolinska Institute, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden;
Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1393-401. doi: 10.2215/CJN.11901113. Epub 2014 Jun 12.
Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).
During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).
These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.
肾损伤分子-1（KIM-1）已被认为是急性肾小管损伤具有临床相关性的高度特异性生物标志物。然而，缺乏基于社区的KIM-1尿水平与心血管死亡风险之间关联的数据。本研究旨在调查尿KIM-1与心血管死亡之间的关联。
设计、设置、参与者及测量：这是一项前瞻性研究，采用基于社区的乌普萨拉成年男性纵向研究（N = 590；平均年龄77岁；基线期，1997 - 2001年；中位随访8.1年；随访结束于2008年）。
在随访期间，89名参与者死于心血管原因（发病率为每100人年有风险人群中2.07例）。模型针对心血管危险因素（年龄、收缩压、糖尿病、吸烟、体重指数、总胆固醇、高密度脂蛋白胆固醇、抗高血压治疗、降脂治疗、阿司匹林治疗以及心血管疾病史）以及肾功能障碍和损伤标志物（基于胱抑素C的估算肾小球滤过率和尿白蛋白/肌酐比值）进行了调整。较高的尿KIM-1/肌酐（来自24小时尿液收集）与心血管死亡风险较高相关（每标准差增加的风险比，1.27；95%置信区间[95%CI]，1.05至1.54；P = 0.01）。与KIM-1/肌酐低（<175 ng/mmol）、估算肾小球滤过率正常（>60 ml/min per 1.73 m²）且尿白蛋白正常（白蛋白/肌酐比值<3 g/mol）的参与者相比，KIM-1/肌酐高（上五分位数，≥175 ng/mmol）、估算肾小球滤过率低（≤60 ml/min per 1.73 m²）且有微量白蛋白尿/大量白蛋白尿（白蛋白/肌酐比值≥3 g/mol）的参与者风险增加超过8倍（风险比，8.56；95%CI，4.17至17.56；P < 0.001）。
这些发现表明，较高的尿KIM-1可能独立于已确定的心血管危险因素、估算肾小球滤过率和蛋白尿而使心血管死亡风险更高。需要进一步研究以进一步评估在临床环境中测量KIM-1的效用。
