Effect of pentoxifylline on renal toxicity of cyclosporine: results of a clinical trial after heart transplantation.
BACKGROUND
Pentoxifylline was suggested to prevent the renal release of endothelin caused by cyclosporine.


METHODS
We studied the renal-sparing effect of pentoxifylline in 44 patients who underwent heart transplantation between 1991 and 1994 and were randomized to a group treated with pentoxifylline (400 mg three times daily) or to a control group. All patients were treated according to the same immunosuppression protocol, including induction with perioperative rabbit anti-thymocyte antibody and maintenance with azathioprine, cyclosporine, and prednisone. Five patients withdrew voluntarily because of lack of compliance, and five patients died during the first month of the study.


RESULTS
There was no difference between the two groups in regard to age, sex, initial cardiopathy, the number of acute rejections, and the number of infection episodes. Urinary clearance of creatinine averaged 1.1 +/- 0.1 ml/sec, 1.3 +/- 0.1 ml/sec, and 1.3 +/- 0.1 ml/sec in the control patients (n = 16) and 1.2 +/- 0.1 ml/sec, 1.4 +/- 0.1 ml/sec, and 1.3 ml/sec in patients treated with pentoxifylline (n = 18) at initiation, 12 months, and 24 months of the study (p > 0.05), respectively. At these three times, the serum creatinine levels averaged 106 +/- 4 mmol/L, 119 +/- 4 mmol/L, and 126 +/- 5 mmol/L in the control group and 94 +/- 4 mmol/L, 114 +/- 4 mmol/L, and 127 +/- 5 mmol/L in patients treated with pentoxifylline, respectively (p > 0.05). Trough levels of cyclosporine throughout the study period averaged 212 +/- 8 mmol/L and 206 +/- 8 mmol/L in the control and treated groups, respectively (p > 0.05). Endothelin blood levels averaged 0.4 +/- 0.2 pg/ml for nine control patients and 0.4 +/- 0.1 pg/ml for a group of 10 patients treated with pentoxifylline (p > 0.05).


CONCLUSIONS
Pentoxifylline in association with cyclosporine did not result in a significant improvement in renal function during the first 2 years after heart transplantation.
Carrier
M
M
Montreal Heart Institute, Quebec, Canada.
Pelletier
G B
GB
White
M
M
Bois
D
D
Pelletier
L C
LC
D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000633:toxicity*; D016232:Endothelins / Q000378:metabolism; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000627:therapeutic use*; D011446:Prospective Studies; D014665:Vasodilator Agents / Q000627:therapeutic use*
D016232:Endothelins; D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D016572:Cyclosporine; D003404:Creatinine; D010431:Pentoxifylline