Beneficial effects of pentoxifylline on cyclosporine-induced nephrotoxicity.

1. Hypertension and renal failure are the two most common and severe complications due to cyclosporine A (CsA) therapy after transplantation. To determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the toxic effects of CsA, three groups of rats were studied. 2. The first group of rats (n = 11) received daily injections of CsA (15 mg/kg, i.m.) and PTX (45 mg/kg, i.p., b.i.d.), the second group of rats (n = 11) was treated with CsA only and the third group of rats (n = 11) served as the control group (vehicle treatment). 3. Whole blood CsA levels were similar in CsA + PTX and CsA alone groups. Although CsA treatment significantly increased mean arterial blood pressure (110.00 +/- 2.48 mmHg; P < 0.01), there was no significant increase in the PTX co-treated group (104.09 +/- 2.96 mmHg) compared with initial values. In both the CsA alone and CsA + PTX groups the heart rate (365.45 +/- 6.65 and 357.27 +/- 7.23 b.p.m., respectively; P < 0.05) were found to be significantly higher than initial values. Serum creatinine levels increased significantly in the CsA alone group (1.40 +/- 0.11 mg/dL; P < 0.01) compared with control values (0.81 +/- 0.04 mg/dL). This increase was prevented by co-treatment with PTX (serum creatinine 1.11 +/- 0.01 mg/dL; P < 0.05). Total [99mTc]-DTPA percentage renal uptake, as an index of glomerular filtration rate (GFR), was markedly and significantly lower in the CsA alone group (10.01 +/- 0.79%; P < 0.01) than in the control group (18.19 +/- 1.32%). Pentoxifylline co-treatment attenuated this decrease compared with GFR in the CsA alone group (13.00 +/- 0.75%; P < 0.01). 4. These results suggest that the co-administration of PTX with CsA may prevent the dose-limiting toxic effects of CsA therapy.