Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Internal Medicine, Section of Cardiovascular Medicine.
Clin J Am Soc Nephrol. 2019 May 7;14(5):712-718. doi: 10.2215/CJN.11600918. Epub 2019 Apr 22.
Diuretic resistance can limit successful decongestion of patients with heart failure. Because loop diuretics tightly bind albumin, low serum albumin and high urine albumin can theoretically limit diuretic delivery to the site of action. However, it is unknown if this represents a clinically relevant mechanism of diuretic resistance in human heart failure.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 208 outpatients with heart failure at the Yale Transitional Care Center undergoing diuretic treatment were studied. Blood and urine chemistries were collected at baseline and 1.5 hours postdiuretic administration. Urine diuretic levels were normalized to urine creatinine and adjusted for diuretic dose administered, and diuretic efficiency was calculated as sodium output per doubling of the loop diuretic dose. Findings were validated in an inpatient heart failure cohort (=60).
Serum albumin levels in the outpatient cohort ranged from 2.4 to 4.9 g/dl, with a median of 3.7 g/dl (interquartile range, 3.5-4.1). Serum albumin had no association with urinary diuretic delivery (=-0.05; =0.52), but higher levels weakly correlated with better diuretic efficiency (=0.17; =0.02). However, serum albumin inversely correlated with systemic inflammation as assessed by plasma IL-6 (=-0.35; <0.001), and controlling for IL-6 eliminated the diuretic efficiency-serum albumin association (=0.12; =0.12). In the inpatient cohort, there was no association between serum albumin and urinary diuretic excretion (=0.15; =0.32) or diuretic efficiency (=-0.16; =0.25). In the outpatient cohort, 39% of patients had microalbuminuria, and 18% had macroalbuminuria. There was no correlation between albuminuria and diuretic efficiency after adjusting for kidney function (=-0.02; =0.89). Results were similar in the inpatient cohort.
Serum albumin levels were not associated with urinary diuretic excretion, and urinary albumin levels were not associated with diuretic efficiency.
利尿剂抵抗会限制心力衰竭患者成功消肿。由于袢利尿剂与白蛋白紧密结合,因此理论上血清白蛋白低和尿白蛋白高会限制利尿剂到达作用部位。然而,目前尚不清楚这是否代表心力衰竭患者中利尿剂抵抗的一种临床相关机制。
设计、设置、参与者和测量:共有 208 名在耶鲁过渡护理中心接受利尿剂治疗的心力衰竭门诊患者参与了本研究。在给予利尿剂后 1.5 小时采集血和尿化学物质。将尿利尿剂水平标准化为尿肌酐,并根据给予的利尿剂剂量进行调整,利尿剂效率计算为每加倍给予袢利尿剂剂量的钠输出量。在住院心力衰竭队列(=60)中验证了发现。
门诊患者队列的血清白蛋白水平范围为 2.4 至 4.9 g/dl,中位数为 3.7 g/dl(四分位距,3.5-4.1)。血清白蛋白与尿利尿剂输送无关联(=-0.05;=0.52),但较高水平与更好的利尿剂效率呈弱相关(=0.17;=0.02)。然而,血清白蛋白与通过血浆 IL-6 评估的全身炎症呈负相关(=-0.35;<0.001),控制 IL-6 后消除了利尿剂效率-血清白蛋白的关联(=0.12;=0.12)。在住院患者队列中,血清白蛋白与尿利尿剂排泄(=0.15;=0.32)或利尿剂效率(=-0.16;=0.25)之间没有关联。在门诊患者队列中,39%的患者有微量白蛋白尿,18%的患者有大量白蛋白尿。调整肾功能后,白蛋白尿与利尿剂效率之间无相关性(=-0.02;=0.89)。住院患者队列中的结果相似。
血清白蛋白水平与尿利尿剂排泄无关,尿白蛋白水平与利尿剂效率无关。