Fenoldopam reverses cyclosporine-induced renal vasoconstriction in kidney transplant recipients.
Cyclosporine causes renal vasoconstriction and reduced renal blood flow that may contribute to chronic nephrotoxicity. This effect has not been consistently reversed by available pharmacologic agents. The efficacy of orally administered fenoldopam, a dopamine-1 (DA-1) agonist with renal vasodilator properties, was evaluated in six patients whose condition was stable 3 to 6 months following renal transplantation. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate (PAH) clearances, respectively, at baseline, after the acute oral administration of 100 mg of fenoldopam, and following 3 weeks of chronic oral fenoldopam therapy (100 mg thrice daily). Mean ERPF increased from 3.15 +/- 0.17 mL/s/1.73 m2 (189 +/- 10 mL/min/1.73 m2) at baseline to 3.48 +/- 0.17 mL/s/1.73 m2 (209 +/- 10 mL/min/1.73 m2) 4 hours after acute administration of fenoldopam (P = 0.04). Urine flow rate and fractional excretion of sodium also increased after acute administration, but not significantly. Mean systolic (SBP) and diastolic blood pressure (DBP) decreased maximally by 18 and 6 mm Hg, respectively, and mean pulse rate increased maximally by 8 bpm between 75 and 90 minutes after both acute and chronic administration. GFR was unchanged following both acute and chronic administration. The increase in ERPF was not maintained to the end of the dosing interval during chronic administration, probably due to the short half-life of fenoldopam. However, the renal vasodilatory response was still observed 3 to 4 hours after readministration of the drug following 3 weeks of oral dosing. Thus, fenoldopam significantly reverses the renal vasoconstriction caused by cyclosporine in renal transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
Jorkasky
D K
DK
Presbyterian Medical Center of Philadelphia, PA 19104.
Audet
P
P
Shusterman
N
N
Ilson
B
B
Dafoe
D
D
Hedrich
D
D
Stote
R M
RM
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D016572:Cyclosporine / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D015259:Dopamine Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018818:Fenoldopam; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D015259:Dopamine Agents; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016572:Cyclosporine; D018818:Fenoldopam