Owan Theophilus E, Chen Horng H, Frantz Robert P, Karon Barry L, Miller Wayne L, Rodeheffer Richard J, Hodge David O, Burnett John C, Redfield Margaret M
Mayo Clinic College of Medicine, Division of Cardiovascular Diseases, Rochester, Minneosta 55905.
J Card Fail. 2008 May;14(4):267-75. doi: 10.1016/j.cardfail.2007.12.002.
Strategies to preserve renal function and enhance diuretic responsiveness during therapy for heart failure (HF) are needed. We hypothesized that brain natriuretic peptide (nesiritide) added to standard HF therapy would preserve renal function and enhance diuretic responsiveness.
Patients with HF with underlying renal dysfunction who were admitted with volume overload were randomized to standard therapy with nesiritide (2 mug/kg bolus; 0.01 mug/kg/min for 48 hours) or without nesiritide. Patients requiring intravenous vasodilator or inotropic therapy for rapid symptom relief were ineligible. In all patients, diuretics were administered according to a standardized dosing algorithm.
Patients (n = 72) had a mean creatinine level of 1.75 +/- 0.59 mg/dL. Patients receiving nesiritide had a lesser increase in creatinine (P = .048) and blood urea nitrogen (P = .02), but a greater reduction in blood pressure (P < .01). Nesiritide did not enhance diuretic responsiveness (P = .57) but increased 3'5' cyclic guanosine monophosphate and decreased endothelin more (P < .05 for both). There were no differences in the change in atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide, plasma renin activity, angiotensin II, and aldosterone between groups.
When used as adjuvant "renal protective" therapy in patients with HF with renal dysfunction, the recommended dose of nesiritide reduced blood pressure, did not seem to worsen renal function, and suppressed endothelin but did not enhance diuretic responsiveness or prevent activation of the renin-angiotensin-aldosterone system.
在心力衰竭(HF)治疗期间,需要采取策略来保护肾功能并增强利尿反应性。我们假设,在标准HF治疗中添加脑钠肽(奈西立肽)可保护肾功能并增强利尿反应性。
因容量超负荷入院的合并潜在肾功能不全的HF患者被随机分为接受奈西立肽标准治疗组(2μg/kg静脉推注;0.01μg/kg/分钟,持续48小时)或不接受奈西立肽组。需要静脉使用血管扩张剂或正性肌力药物以快速缓解症状 的患者不符合入组标准。所有患者均按照标准化给药方案使用利尿剂。
患者(n = 72)的平均肌酐水平为1.75±0.59mg/dL。接受奈西立肽治疗的患者肌酐(P = 0.048)和血尿素氮(P = 0.02)的升高幅度较小,但血压下降幅度更大(P < 0.01)。奈西立肽未增强利尿反应性(P = 0.57),但3',5'-环磷酸鸟苷增加更多,内皮素降低更多(两者P均< 0.05)。两组之间心房利钠肽、N末端脑钠肽原、血浆肾素活性、血管紧张素II和醛固酮的变化无差异。
当奈西立肽用于合并肾功能不全的HF患者的辅助“肾脏保护”治疗时,推荐剂量可降低血压,似乎不会使肾功能恶化,并可抑制内皮素,但不会增强利尿反应性或预防肾素-血管紧张素-醛固酮系统的激活。