Prophylactic isradipine treatment after kidney transplantation: a prospective double-blind placebo-controlled randomized trial.
There is evidence that calcium antagonists may have a beneficial effect on cyclosporine-induced nephropathy after transplantation. We treated 50 consecutive non-diabetic patients receiving their first cadaveric transplant with isradipine, a dihydropyridine calcium antagonist, or placebo in a double-blind, randomized, placebo-controlled trial. There were no significant differences between the two groups as regards age, weight, sex, HLA matching and ischaemic periods. To achieve optimal vasodilation, treatment was started intravenously 2 h before the transplantation procedure, and continued orally afterwards for 3 months. The immunosuppressive treatment included rabbit antithymocyte globulin on day 0, and oral cyclosporine from day 5. In both groups 7 patients had primary non-functioning grafts, but the incidence of never functioning kidneys due to vascular and thrombotic complications was significantly higher in the placebo group (0 vs 4 patients, P < 0.05). Hypertension was treated with oral labetolol in combination with guanfacine if necessary. In the placebo group antihypertensive medication had to be prescribed significantly more often (67% vs 33% of patients, P < 0.05), but resulted in similar blood pressure recordings in the two study groups. Cyclosporin A (CsA) plasma concentrations were also comparable but in the isradipine group a significantly higher dose of CsA was needed to achieve adequate levels (8.0 +/- 0.5 vs 6.2 +/- 0.5 mg/kg per day, P < 0.01). However, in the isradipine-treated patients creatinine clearance was significantly higher (66.1 +/- 4.5 vs 55.6 +/- 6.2 ml/min, P < 0.05) after 3 months. We conclude that isradipine is an effective antihypertensive agent after kidney transplantation. Isradipine ameliorates CsA-induced nephropathy and seems to protect against early postoperative vascular complications.
van den Dorpel
M A
MA
Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Zietse
R
R
Ijzermans
J N
JN
Weimar
W
W
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017275:Isradipine / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011183:Postoperative Complications / Q000517:prevention & control*; D014019:Tissue Donors
D000961:Antilymphocyte Serum; D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D010919:Placebos; D016572:Cyclosporine; D006854:Hydrocortisone; D017275:Isradipine