Wettersten Nicholas, Katz Ronit, Ascher Simon B, Scherzer Rebecca, Bullen Alexander L, Chen Teresa K, Campos Kasey, Garimella Pranav S, Estrella Michelle M, Shlipak Michael G, Ix Joachim H
Cardiology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA.
Division of Cardiology, Department of Medicine, University of California San Diego, San Diego, CA.
Kidney Med. 2025 May 14;7(7):101024. doi: 10.1016/j.xkme.2025.101024. eCollection 2025 Jul.
RATIONALE & OBJECTIVE: Among individuals with chronic kidney disease (CKD), higher blood levels of kidney injury molecule-1 (KIM-1) and soluble tumor necrosis factor receptors (TNFR-1 and TNFR-2) have been associated with greater risk of CKD progression. Their associations with risk of cardiovascular disease (CVD) and all-cause mortality in individuals with CKD remain uncertain. STUDY DESIGN: An observational cohort study. SETTING & PARTICIPANTS: Systolic Blood Pressure Intervention Trial participants with hypertension and CKD (eGFR <60 mL/min/1.73 m) but without diabetes. PREDICTORS: Plasma KIM-1, TNFR-1, and TNFR-2. OUTCOMES: A composite CVD outcome (acute coronary syndrome/myocardial infarction, stroke, heart failure, and CVD death) and all-cause mortality. ANALYTIC APPROACH: Cox proportional hazards models, adjusting for CVD risk factors, eGFR, and urine albumin-to-creatinine ratio. RESULTS: Total of 2,350 participants with a mean age of 73 ± 9 years, eGFR of 46 ± 10 mL/min/1.73m and 25% prevalence of CVD. Over more than 3 years follow-up, 293 CVD events (12%) and 160 deaths (7%) occurred. Higher KIM-1, TNFR-1, and TNFR-2 were associated with higher risk of the composite CVD outcome after adjusting for CVD risk factors, but associations were no longer significant after adjusting for eGFR and urine albumin-to-creatinine ratio (KIM-1: HR = 1.13, 95% CI, 0.99-1.30; TNFR-1: HR = 1.03, 95% CI, 0.72-1.46; TNFR-2: HR = 0.98, 95% CI, 0.76-1.26). In contrast, in fully adjusted models, higher plasma KIM-1 and TNFR-1, but not TNFR-2, were associated with higher risk of all-cause mortality (KIM-1: HR = 1.23, 95% CI, 1.01-1.49; TNFR-1: HR = 2.09, 95% CI, 1.14-3.83; TNFR-2: HR = 1.19, 95% CI, 0.85-1.66). LIMITATIONS: No individuals with diabetes or stroke. CONCLUSIONS: In individuals with hypertension and nondiabetic CKD, associations of higher plasma KIM-1, TNFR-1, and TNFR-2 concentrations with CVD events were not independent of eGFR and albuminuria, whereas higher levels of plasma KIM-1 and TNFR-1 were independently associated with greater risk of all-cause mortality.
原理与目的：在慢性肾脏病（CKD）患者中，较高的血肾损伤分子-1（KIM-1）水平及可溶性肿瘤坏死因子受体（TNFR-1和TNFR-2）水平与CKD进展风险增加相关。它们与CKD患者心血管疾病（CVD）风险及全因死亡率的关联仍不明确。 研究设计：一项观察性队列研究。 研究地点与参与者：收缩压干预试验中患有高血压和CKD（估算肾小球滤过率[eGFR]<60ml/min/1.73m²）但无糖尿病的参与者。 预测因素：血浆KIM-1、TNFR-1和TNFR-2。 研究结果：复合CVD结局（急性冠脉综合征/心肌梗死、中风、心力衰竭和CVD死亡）及全因死亡率。 分析方法：Cox比例风险模型，对CVD危险因素、eGFR和尿白蛋白与肌酐比值进行校正。 结果：共有2350名参与者，平均年龄73±9岁，eGFR为46±10ml/min/1.73m²，CVD患病率为25%。在超过3年的随访中，发生了293例CVD事件（12%）和160例死亡（7%）。校正CVD危险因素后，较高的KIM-1、TNFR-1和TNFR-2与复合CVD结局风险较高相关，但在校正eGFR和尿白蛋白与肌酐比值后，相关性不再显著（KIM-1：风险比[HR]=1.13，95%置信区间[CI]，0.99-1.30；TNFR-1：HR=1.03，95%CI，0.72-1.46；TNFR-2：HR=0.98，95%CI，0.76-1.26）。相比之下，在完全校正模型中，较高的血浆KIM-1和TNFR-1，但不包括TNFR-2，与全因死亡率风险较高相关（KIM-1：HR=1.23，95%CI，1.01-1.49；TNFR-1：HR=2.09，95%CI，1.14-3.83；TNFR-2：HR=1.19，95%CI，0.85-1.66）。 局限性：无糖尿病或中风患者。 结论：在患有高血压和非糖尿病CKD的个体中，较高的血浆KIM-1、TNFR-1和TNFR-2浓度与CVD事件的关联并非独立于eGFR和蛋白尿，而较高的血浆KIM-1和TNFR-1水平与全因死亡率风险增加独立相关。
Cochrane Database Syst Rev. 2025-2-18
Cochrane Database Syst Rev. 2022-2-24
Cochrane Database Syst Rev. 2025-5-6
Cochrane Database Syst Rev. 2024-10-15
Cochrane Database Syst Rev. 2021-11-5
Cochrane Database Syst Rev. 2018-9-24
Cochrane Database Syst Rev. 2023-7-19
Am J Kidney Dis. 2025-3-5
Int J Mol Sci. 2022-10-26
J Am Soc Nephrol. 2022-5
Clin J Am Soc Nephrol. 2022-2
Signal Transduct Target Ther. 2021-7-12
Zotero 插件
