Shusterman N H, Elliott W J, White W B
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
Am J Med. 1993 Aug;95(2):161-8. doi: 10.1016/0002-9343(93)90256-o.
Patients with hypertensive crises often experience reduced renal function that may worsen as the elevated blood pressure is treated. Fenoldopam, a novel, peripherally acting dopamine-1 agonist, lowers blood pressure through arteriolar vasodilation, with particularly prominent effects on the renal vascular bed. This study was conducted to examine the effects of fenoldopam on blood pressure and renal function compared to those of sodium nitroprusside in severely hypertensive patients with impaired renal function.
Renal function and systemic hemodynamics were studied in 19 severely hypertensive patients (diastolic blood pressure greater than or equal to 120 mm Hg) with impaired renal function (creatinine clearance less than or equal to 70 mL/min) enrolled in clinical trials of fenoldopam and sodium nitroprusside. For comparison, an additional 22 severely hypertensive patients with nonimpaired renal function were studied under the same conditions. Blood pressure and heart rate were measured at baseline before treatment and periodically during treatment. Renal function was determined before and during drug infusion by collection of timed urine specimens and blood samples. Creatinine clearance, urine flow rate, and sodium and potassium excretions were measured and compared.
In patients with impaired renal function, blood pressure (mean +/- SEM) was reduced successfully in both groups (fenoldopam: 214 +/- 8/139 +/- 6 mm Hg to 176 +/- 8/107 +/- 3 mm Hg, p < 0.001 for systolic and diastolic comparisons; nitroprusside: 226 +/- 4/145 +/- 5 mm Hg to 171 +/- 6/108 +/- 2 mm Hg, p < 0.001 for systolic and diastolic comparisons). Results of renal function studies showed significant increases in creatinine clearance (from 39 +/- 7 mL/min to 75 +/- 16 mL/min, p < 0.05), urine flow (from 119 +/- 37 mL/h to 275 +/- 84 mL/h, p < 0.01), and sodium excretion (from 75 +/- 22 microEq/min to 227 +/- 60 microEq/min, p < 0.01) in patients with impaired renal function treated with fenoldopam. No significant changes were seen in patients treated with nitroprusside. In patients with nonimpaired renal function, blood pressure was reduced by both agents, but only patients who received fenoldopam experienced significant increases in creatinine clearance, urine flow rate, and sodium excretion.
Fenoldopam, but not nitroprusside, improved renal function in severely hypertensive patients at all levels of baseline renal function while lowering blood pressure. Because of these effects, fenoldopam may be particularly useful in treating severely hypertensive patients with impaired renal function.
高血压危象患者常出现肾功能减退,且随着血压升高的治疗,肾功能可能会恶化。非诺多泮是一种新型的外周作用多巴胺-1激动剂,通过小动脉血管舒张降低血压,对肾血管床有特别显著的作用。本研究旨在比较非诺多泮与硝普钠对肾功能受损的重度高血压患者血压和肾功能的影响。
在参与非诺多泮和硝普钠临床试验的19例肾功能受损(肌酐清除率小于或等于70 mL/分钟)的重度高血压患者(舒张压大于或等于120 mmHg)中研究肾功能和全身血流动力学。为作比较,在相同条件下研究另外22例肾功能未受损的重度高血压患者。在治疗前的基线以及治疗期间定期测量血压和心率。通过收集定时尿液标本和血液样本,在药物输注前和输注期间测定肾功能。测量并比较肌酐清除率、尿流率以及钠和钾排泄量。
在肾功能受损的患者中,两组患者的血压(平均值±标准误)均成功降低(非诺多泮组:收缩压214±8 mmHg、舒张压139±6 mmHg降至收缩压176±8 mmHg、舒张压107±3 mmHg,收缩压和舒张压比较,p<0.001;硝普钠组:收缩压226±4 mmHg、舒张压145±5 mmHg降至收缩压171±6 mmHg、舒张压108±2 mmHg,收缩压和舒张压比较,p<0.001)。肾功能研究结果显示,接受非诺多泮治疗的肾功能受损患者的肌酐清除率(从39±7 mL/分钟增至75±16 mL/分钟,p<0.05)、尿流(从119±37 mL/小时增至275±84 mL/小时,p<0.01)和钠排泄(从75±22微当量/分钟增至227±60微当量/分钟,p<0.01)均显著增加。接受硝普钠治疗的患者未见显著变化。在肾功能未受损的患者中,两种药物均降低了血压,但只有接受非诺多泮治疗的患者肌酐清除率、尿流率和钠排泄有显著增加。
非诺多泮而非硝普钠在降低血压的同时改善了所有基线肾功能水平的重度高血压患者的肾功能。由于这些作用,非诺多泮可能对治疗肾功能受损的重度高血压患者特别有用。