Background. Erythrocytosis occurs in 10 to 15 percent of renal-transplant recipients, and there is in vitro evidence that the production of erythropoietin is modulated by adenosine. Methods. We prospectively evaluated the effects of theophylline, a nonselective adenosine antagonist, in eight patients with erythrocytosis after renal transplantation and in five normal controls. Results. After an eight-week course of theophylline treatment, the mean (±SEM) serum erythropoietin levels were significantly reduced in both the renal-transplant recipients (from 60±14 units per liter at base line to 9±7 units after treatment; P<0.05) and the normal subjects (from 6.9±0.8 units per liter at base line to 4.7±0.5 units per liter after treatment; P<0.05). Similarly, the hematocrits were reduced in both the transplant recipients (from 0.58±0.04 at base line to 0.46±0.03 after treatment; P<0.05) and the normal subjects (from 0.43±0.01 at base line to 0.39±0.01; P<0.05). In the renal-transplant recipients, red-cell mass was also reduced after eight weeks of theophylline (from 3197±82 ml at base line to 2273±69 ml after treatment; P<0.05). The previous requirement of weekly phlebotomy was eliminated in all recipients. Plasma and urinary cyclic AMP levels were not increased. These effects were reproducible when the subjects were rechallenged with theophylline after a recovery period. Conclusions. Theophylline attenuates the production of erythropoietin both normal subjects and patients with erythrocytosis after renal transplantation and may be useful in the treatment of the latter condition.
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