Effects of theophylline on erythropoietin production in normal subjects and in patients with erythrocytosis after renal transplantation.
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 less than 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 less than 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 less than 0.05) and the normal subjects (from 0.43 +/- 0.01 at base line to 0.39 +/- 0.01; P less than 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 less than 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 in both normal subjects and patients with erythrocytosis after renal transplantation and may be useful in the treatment of the latter condition.
Bakris
G L
GL
Department of Medicine, Ochsner Medical Institutions, New Orleans, LA.
Sauter
E R
ER
Hussey
J L
JL
Fisher
J W
JW
Gaber
A O
AO
Winsett
R
R
D000328:Adult; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D004921:Erythropoietin / Q000096:biosynthesis*; D005260:Female; D006400:Hematocrit; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011086:Polycythemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D011183:Postoperative Complications / Q000378:metabolism; D011446:Prospective Studies; D013806:Theophylline / Q000494:pharmacology* / Q000627:therapeutic use
D004921:Erythropoietin; D013806:Theophylline; D000242:Cyclic AMP