背景:慢性心力衰竭(CHF)患者是否易于肾小管损害,在临床结局之前肾功能恶化(WRF)。
目的:肾小管损伤生物标志物的变化比肌酐(Cr)的变化更能预测后续临床事件,两者都有不同的临床决定因素。
方法:在2.2年间,在263例CHF患者中,我们同时重复收集了每位患者的中位9份血液和8份尿液样本.我们确定了血浆(Cr)和尿小管损伤生物标志物N-乙酰-β-d-氨基葡萄糖苷酶(NAG)的生物标志物轨迹的斜率(变化率),和肾损伤分子(KIM)-1。根据NAG和KIM-1斜率对肾小管损伤程度进行排序:两者均未增加,要么增加,或两者都增加;WRF定义为增加Cr斜率。复合终点包括HF住院,心脏死亡,左心室辅助装置放置,心脏移植。
结果:较高的基线NT-proBNP和较低的eGFR预测更严重的肾小管损伤(调整后的比值比,adj.或[95CI,95%置信区间]NT-proBNP每加倍:1.26[1.07-1.49];每10mL/min/1.73m2eGFR降低1.16[1.03-1.31])。更高的环路利尿剂剂量,较低的醛固酮拮抗剂剂量,和更高的eGFR预测WRF(呋塞米每40mg增加:1.32[1.08-1.62];螺内酯每25mg减少:1.76[1.07-2.89];每10mL/min/1.73m2eGFR增加:1.40[1.20-1.63])。WRF和较高等级的肾小管损伤单独导致较高的复合终点风险(调整后的风险比,adj.HR[95CI]:WRF1.9[1.1-3.4],管8.4[2.6-27.9];当综合风险最高15.0[2.0-111.0]时)。
结论:肾小管损伤斜率和WRF生物标志物具有不同的临床决定因素。两者都预测了临床结果,但这种关联在肾小管损伤中更强。两者的预后效应似乎是独立的和相加的。
BACKGROUND: It is uncertain that chronic heart failure (CHF) patients are susceptible to renal tubular damage with that of worsening renal function (WRF) preceding clinical outcomes.
OBJECTIVE: Changes in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants.
METHODS: During 2.2 years, we repeatedly simultaneously collected a median of 9 blood and 8 urine samples per patient in 263 CHF patients. We determined the slopes (rates of change) of the biomarker trajectories for plasma (Cr) and urinary tubular damage biomarkers N-acetyl-β-d-glucosaminidase (NAG), and kidney-injury-molecule (KIM)-1. The degree of tubular injury was ranked according to NAG and KIM-1 slopes: increase in neither, increase in either, or increase in both; WRF was defined as increasing Cr slope. The composite endpoint comprised HF-hospitalization, cardiac death, left ventricular assist device placement, and heart transplantation.
RESULTS: Higher baseline NT-proBNP and lower eGFR predicted more severe tubular damage (adjusted odds ratio, adj. OR [95%CI, 95% confidence interval] per doubling NT-proBNP: 1.26 [1.07-1.49]; per 10 mL/min/1.73 m2 eGFR decrease 1.16 [1.03-1.31]). Higher loop diuretic doses, lower aldosterone antagonist doses, and higher eGFR predicted WRF (furosemide per 40 mg increase: 1.32 [1.08-1.62]; spironolactone per 25 mg decrease: 1.76 [1.07-2.89]; per 10 mL/min/1.73 m2 eGFR increase: 1.40 [1.20-1.63]). WRF and higher rank of tubular injury individually entailed higher risk of the composite endpoint (adjusted hazard ratios, adj. HR [95%CI]: WRF 1.9 [1.1-3.4], tubular 8.4 [2.6-27.9]; when combined risk was highest 15.0 [2.0-111.0]).
CONCLUSIONS: Slopes of tubular damage and WRF biomarkers had different clinical determinants. Both predicted clinical outcome, but this association was stronger for tubular injury. Prognostic effects of both appeared independent and additive.