Improvement in renal function by felodipine during cyclosporine treatment in acute and short-term studies.
The purpose was to study whether the calcium entry blocker, felodipine, could reduce the nephrotoxic and hypertensive effect of cyclosporine. The effect of felodipine on glomerular filtration rate (GFR), renal plasma flow (RPF), fractional excretion of sodium, lithium clearance and blood pressure was measured in three randomized, placebo-controlled studies of cyclosporine treated patients. In study one, 10 renal transplant recipients were examined within the first six months after transplantation in a cross-over design. Renal hemodynamics were determined after the acute ingestion of felodipine or placebo, with an interval of less than one week between the two examinations. In study two, 79 renal transplant recipients were randomized to a treatment with felodipine or placebo just before transplantation, and renal hemodynamics were determined after twelve weeks. In study three, 18 patients, who were treated with cyclosporine due to dermatological diseases, were examined in a cross-over design to determine their renal hemodynamics after four weeks of treatment with felodipine or placebo. Felodipine increased renal hemodynamics in study one (GFR 16%, RPF 33%, P < 0.01 for both), in study two (GFR 23%, RPF 28%, P < 0.05 for both), and in study three (GFR 13%, RPF 26%, P < 0.01 for both). FE(Na) was significantly increased by felodipine in studies one and three, but not in study two. Lithium clearance was significantly increased and blood pressure significantly reduced by felodipine in all three studies. It can be concluded that felodipine counteracts both the cyclosporine induced impairment in renal hemodynamics and the increase in blood pressure in acute and short-term studies.
Pedersen
E B
EB
Research Laboratory of Nephrology and Hypertension, University Hospital, Aarhus, Denmark.
Madsen
J K
JK
Sørensen
S S
SS
Zachariae
H
H
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D015736:Felodipine / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects; D008094:Lithium / Q000652:urine; D008297:Male; D012079:Renal Circulation / Q000187:drug effects
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008094:Lithium; D015736:Felodipine