Acute effects of nifedipine in renal transplant recipients treated with cyclosporine or azathioprine.
Cyclosporine (CsA) impairs renal function, probably by preglomerular vasoconstriction. Vasodilating substances may therefore be of benefit to ameliorate CsA-induced renal dysfunction. We studied the acute effects on blood pressure and renal function of the dihydropyridine calcium antagonist nifedipine (10 mg orally) in 20 CsA-treated renal transplant patients. In addition, we compared the effects of nifedipine when given immediately before and 4 weeks after elective conversion from CsA to azathioprine. Compared with placebo (n = 14), administration of nifedipine led to a significant decrease in blood pressure and a strong natriuretic and diuretic response. Despite the reduction in blood pressure, glomerular filtration rate improved from 60 +/- 20 (mean +/- SD) to 69 +/- 24 mL/min/1.73 m2 (P < 0.001) and renal plasma flow (RPF) increased from 260 +/- 87 to 338 +/- 120 mL/min/1.73 m2 (P < 0.001). The combination of a decreased blood pressure with an increased RPF was reflected in a sharp decrease in renal vascular resistance (0.34 +/- 0.18 units v 0.23 +/- 0.10 units; P < 0.001). The conversion from CsA to azathioprine by itself led to significant increases in glomerular filtration rate (62 +/- 15 mL/min/1.73 m2 v 76 +/- 18 mL/min/1.73 m2; P < 0.05) and RPF (280 +/- 86 mL/min/1.73 m2 v 334 +/- 66 mL/min/1.73 m2; P < 0.05). During treatment with azathioprine an effect of nifedipine on glomerular filtration rate and RPF was no longer observed, although the natriuretic effect was similar on both occasions. The decrease in renal vascular resistance was larger during treatment with CsA than during treatment with azathioprine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Hilbrands
L B
LB
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Hoitsma
A J
AJ
van Hamersvelt
H W
HW
Wetzels
J F
JF
Huysmans
F T
FT
Koene
R A
RA
D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D004231:Diuresis / Q000187:drug effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D017595:Renal Plasma Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D016572:Cyclosporine; D009543:Nifedipine; D001379:Azathioprine