Posttransplant erythrocytosis: a model for the investigation of the pharmacological control of renal erythropoietin production?
Posttransplant erythrocytosis (PTE) is a problem which occurs in 5-10% of renal transplant patients. The pathophysiology of PTE is not yet fully understood but does obviously not simply rely on elevated circulating erythropoietin (EPO) levels. In recent years pharmacological treatment alternatives to phlebotomy have been found. The therapeutic effect of angiotensin-converting enzyme inhibitors (ACEI) is well documented, even though the mechanism of action remains unclear and may not be directly related to the effects on EPO production. The evidence for the action of theophylline in PTE is more circumstantial and its mechanism of action also unclear. From the current state of knowledge one cannot conclude that its adenosine-antagonistic activity is the likely mechanism for the control of EPO levels. The effect of theophylline on erythrocytosis without elevated EPO levels does make a unifying hypothesis even more difficult. Therefore, PTE should not be used as a model disease to draw conclusions on the physiological control of EPO production, even though there appears to be a subgroup of patients that respond to pharmacological treatment with a reduction of erythrocytosis and of EPO levels. The question whether this is an accompanying phenomenon or a true effect on the underlying etiology can not be answered at present. From a practical point of view, after excluding secondary causes, treatment of PTE should be carried out with low doses of ACEI in order to achieve a reliable therapeutic effect.
Gleiter
C H
CH
Abteilung Klinische Pharmakologie, Georg-August-Universität, Göttingen, Germany.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000096:biosynthesis*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects*; D011086:Polycythemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D004921:Erythropoietin; D013806:Theophylline