Brankovic Milos, Akkerhuis K Martijn, Hoorn Ewout J, van Boven Nick, van den Berge Jan C, Constantinescu Alina, Brugts Jasper, van Ramshorst Jan, Germans Tjeerd, Hillege Hans, Boersma Eric, Umans Victor, Kardys Isabella
Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands.
Clin Cardiol. 2020 Jun;43(6):630-638. doi: 10.1002/clc.23359. Epub 2020 Apr 16.
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.
Changes in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants.
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.
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 m 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 m 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]).
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.
慢性心力衰竭（CHF）患者是否易患肾小管损伤以及肾功能恶化（WRF）是否先于临床结局尚不确定。
肾小管损伤生物标志物的变化比肌酐（Cr）变化更能预测后续临床事件，且两者具有不同的临床决定因素。
在2.2年期间，我们对263例CHF患者反复同时采集血液样本（每位患者中位数为9份）和尿液样本（每位患者中位数为8份）。我们确定了血浆（Cr）和肾小管损伤生物标志物N-乙酰-β-D-氨基葡萄糖苷酶（NAG）以及肾损伤分子（KIM）-1的生物标志物轨迹斜率（变化率）。根据NAG和KIM-1斜率对肾小管损伤程度进行分级：两者均未增加、两者之一增加或两者均增加；WRF定义为Cr斜率增加。复合终点包括心力衰竭住院、心源性死亡、左心室辅助装置置入和心脏移植。
较高的基线NT-proBNP和较低的估算肾小球滤过率（eGFR）预示着更严重的肾小管损伤（NT-proBNP每增加一倍的调整优势比，adj. OR [95%置信区间，95%CI]：1.26 [1.07 - 1.49]；eGFR每降低10 mL/min/1.73m²，调整优势比为1.16 [1.03 - 1.31]）。较高的襻利尿剂剂量、较低的醛固酮拮抗剂剂量和较高的eGFR预示着WRF（呋塞米每增加40mg：1.32 [1.08 - 1.62]；螺内酯每减少25mg：1.76 [1.07 - 2.89]；eGFR每增加10 mL/min/1.73m²：1.40 [1.20 - 1.63]）。WRF和较高等级的肾小管损伤分别导致复合终点风险更高（调整后的风险比，adj. HR [95%CI]：WRF为1.9 [1.1 - 3.4]，肾小管损伤为8.4 [2.6 - 27.9]；两者合并时风险最高，为15.0 [2.0 - 111.0]）。
肾小管损伤和WRF生物标志物的斜率具有不同的临床决定因素。两者均能预测临床结局，但这种关联在肾小管损伤方面更强。两者预测预后的作用似乎是独立且相加的。
