El-Refai Mostafa, Krivospitskaya Olesya, Peterson Edward L, Wells Karen, Williams L Keoki, Lanfear David E
Department of Internal Medicine, Henry Ford Hospital, Detroit MI, 48202, USA.
J Clin Exp Cardiolog. 2011 Nov 22;2(10). doi: 10.4172/2155-9880.1000164.
Worsening renal function (WRF) during heart failure (HF) hospitalization is an accepted correlate of poor prognosis. Loop diuretics are increasingly being considered as a potential cause of worsened HF outcomes, perhaps via WRF. However, the magnitude of worsening in renal function attributable to loop diuretics has not been quantified.
This was a retrospective cohort study of patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between Jan 1, 2000 and June 30, 2008. Patients with preexisting end-stage renal disease were excluded. Daily creatinine (Cr) measurements, furosemide dosing (only loop diuretic on hospital formulary), and radiocontrast dye studies were collected using administrative data. Day-to-day changes in Cr and MDRD estimated glomerular filtration (eGFR) were calculated. The first Cr or eGFR value during hospitalization or in the emergency department was considered baseline. Generalized estimating equations were used to test the association furosemide exposure over previous 2 days to the daily change in Cr and eGFR. Covariates included undergoing radiocontrast study, age, race, gender, and baseline Cr or eGFR.
Among 6071 patients who met inclusion criteria there were a total of 20,645 observations. This cohort was 51% female, 68% African American, and baseline Cr was 1.36 mg/dl. Furosemide exposure was associated with an average daily increase in Cr of 0.021 mg/dL and decrease in eGFR of 0.72 ml/min/1.73m2 (per 100 mg furosemide daily, both p<0.001). Over a typical length of stay of 5 days this would amount to a Cr increase of 0.11 mg/dL or decrease in eGFR of 3.6 ml/min/1.73m. Furosemide exposure accounted for only 0.4% and 0.1% of the variation in Cr and eGFR changes, respectively. Undergoing radiocontrast study, African American race, and higher age were associated with day-to-day creatinine increases (all p<0.01). Reanaysis after classifying furosemide exposure into low (<40mg/day), medium (40-100mg/day), and high (>100mg/day) and censoring patients-days after radiocontrast exposure did not significantly affect the magnitude of the worsening renal function.
While loop diuretic exposure is statistically associated with WRF among hospitalized HF patients, the associated magnitude of renal function change is very small, and loop diuretics explain little of the variability in renal function during hospitalization. More important explanatory factors likely exist but remain unidentified.
心力衰竭（HF）住院期间肾功能恶化（WRF）是公认的预后不良相关因素。袢利尿剂越来越被认为是导致HF结局恶化的一个潜在原因，可能是通过WRF起作用。然而，归因于袢利尿剂的肾功能恶化程度尚未被量化。
这是一项回顾性队列研究，研究对象为2000年1月1日至2008年6月30日期间在一个大型医疗系统接受治疗且出院诊断为HF的患者。排除已患有终末期肾病的患者。使用管理数据收集每日肌酐（Cr）测量值、呋塞米给药剂量（医院处方中唯一的袢利尿剂）以及放射造影剂研究数据。计算Cr和MDRD估计肾小球滤过率（eGFR）的每日变化。住院期间或急诊科的首个Cr或eGFR值被视为基线值。使用广义估计方程来检验过去2天的呋塞米暴露与Cr和eGFR每日变化之间的关联。协变量包括是否接受放射造影剂研究、年龄、种族、性别以及基线Cr或eGFR。
在符合纳入标准的6071例患者中，共有20645次观察。该队列中51%为女性，68%为非裔美国人，基线Cr为1.36mg/dl。呋塞米暴露与Cr平均每日增加0.021mg/dL以及eGFR平均每日降低0.72ml/min/1.73m²相关（每日每100mg呋塞米，p均<0.001）。在典型的5天住院期间，这相当于Cr增加0.11mg/dL或eGFR降低3.6ml/min/1.73m²。呋塞米暴露分别仅占Cr和eGFR变化变异的0.4%和0.1%。接受放射造影剂研究、非裔美国人种族以及较高年龄与每日肌酐增加相关（所有p<0.01）。将呋塞米暴露分为低（<40mg/天）、中（40 - 100mg/天）和高（>100mg/天），并对放射造影剂暴露后的患者天数进行审查后重新分析，并未显著影响肾功能恶化的程度。
虽然在住院HF患者中，袢利尿剂暴露与WRF在统计学上相关，但相关的肾功能变化程度非常小，且袢利尿剂对住院期间肾功能变异性的解释作用很小。可能存在更重要的解释因素，但仍未确定。
