Effects of the calcium antagonist felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in cyclosporin-treated dermatological patients.
BACKGROUND
Deterioration of renal function and rise in blood pressure are clinically important side-effects of cyclosporin (CsA) treatment. Calcium antagonists may have a renoprotective effect against CsA nephrotoxicity.


OBJECTIVE
To investigate the effect of the dihydropyridine calcium-channel blocker felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in CsA-treated patients with no primary renal disease, 18 patients with various CsA-treated dermatological diseases were allocated to receive either felodipine 5 mg (extended release tablets) once daily for 4 weeks followed by placebo for 4 weeks, or vice versa, in a prospective, randomized, double-blind study. The patients were investigated before treatment and at the end of each treatment period.


RESULTS
After felodipine, both glomerular filtration rate (GFR) and renal plasma flow (RPF) were significantly higher compared to placebo (89.4 +/- 17.5 (mean +/- SD) vs 79.0 +/- 15.9 ml/min and 412.0 +/- 107.6 vs 326.1 +/- 78.0 ml/min respectively, P < 0.001 for both), and filtration fraction (FF) was lower (0.22 +/- 0.03 vs 0.25 +/- 0.03, P < 0.001). Both systolic and diastolic blood pressure were lower after felodipine compared to placebo (116 +/- 11/71 +/- 7 vs 133 +/- 18/83 +/- 10 mmHg, P < 0.001 for both). Furthermore, proximal output of sodium, i.e. fractional excretion of lithium, was higher after felodipine (26.9 +/- 7.3% vs 20.4 +/- 5.5%, P < 0.001) as well as total sodium excretion (0.33 +/- 0.19 vs 0.19 +/- 0.08 mmol/min, P < 0.001).


CONCLUSIONS
It is concluded, that felodipine 5 mg once daily for 4 weeks increased GFR, RPF, and sodium excretion in cyclosporin-treated dermatological patients with no primary renal disease. Furthermore, felodipine lowers blood pressure in these patients. The effects of felodipine may be due to an antagonizing effect against CsA-induced nephrotoxicity.
Madsen
J K
JK
Research Laboratory of Nephrology and Hypertension, Aarhus University Hospital, Denmark.
Zachariae
H
H
Pedersen
E B
EB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D015736:Felodipine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012079:Renal Circulation / Q000187:drug effects; D012871:Skin Diseases / Q000188:drug therapy* / Q000503:physiopathology; D012964:Sodium / Q000032:analysis
D002121:Calcium Channel Blockers; D012964:Sodium; D015736:Felodipine