Fenoldopam, but not nitroprusside, improves renal function in severely hypertensive patients with impaired renal function.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Shusterman
N H
NH
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
Elliott
W J
WJ
White
W B
WB
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D003404:Creatinine / Q000378:metabolism; D005260:Female; D018818:Fenoldopam; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012720:Severity of Illness Index; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009599:Nitroprusside; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003404:Creatinine; D018818:Fenoldopam