Effects of losartan or enalapril on hemoglobin, circulating erythropoietin, and insulin-like growth factor-1 in patients with and without posttransplant erythrocytosis.
Both angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists reduce hemoglobin (Hb) levels in patients with posttransplantation erythrocytosis (PTE). However, their effects in transplant recipients without PTE are not certain, and the mechanism by which they reduce Hb levels in patients with PTE remains unclear. This study evaluated the effects of losartan and enalapril on Hb levels in relation to serum erythropoietin (EPO) and insulin-like growth factor-1 (IGF-1) levels in 8 patients with PTE and 10 patients without PTE. All 18 patients were treated sequentially with 24 weeks of losartan therapy, followed by 24 weeks of enalapril therapy; the two treatment phases were separated by a washout period. Patients with PTE showed significantly greater baseline Hb and IGF-1 concentrations compared with patients without PTE before both losartan and enalapril treatments. Baseline serum EPO levels were similar for patients with and without PTE. Baseline Hb level correlated significantly with IGF-1 level (r = 0.517; P = 0.002), but not with EPO level. Treatment with enalapril, 5 mg, reduced Hb levels more markedly than treatment with losartan, 50 mg, in patients with PTE. In patients without PTE, enalapril, 5 mg, mildly reduced Hb levels, whereas losartan, 50 mg, had no significant Hb-lowering effect. The reduction in Hb levels with enalapril therapy in patients with PTE was associated with a significant reduction in circulating IGF-1 levels, but not EPO levels, whereas losartan reduced Hb levels with no significant change in circulating IGF-1 and EPO levels. In patients without PTE, no significant change was noted in serum EPO and IGF-1 levels with either treatment. The differential Hb-lowering effect with losartan and enalapril treatment in patients with and without PTE suggests that the pathogenesis for PTE is complex and heterogeneous. Different erythropoietic mechanisms may be involved in patients with and without PTE. Further large-scale study is needed to determine the exact interaction between the renin-angiotensin system and regulation of IGF-1 and EPO synthesis and define the exact mechanism by which losartan and enalapril reduce Hb levels.
Wang
Angela Yee Moon
AY
Department of Medicine, Center of Clinical Trials and Epidemiological Research, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. awang@cuhk.edu.hk
Yu
Alex Wai Yin
AW
Lam
Christopher Wai Kei
CW
Yu
Ly Mee
LM
Li
Philip Kam Tao
PK
Goh
Juliana
J
Lui
Siu Fai
SF
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology*; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006454:Hemoglobins / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects*; D016030:Kidney Transplantation / Q000009:adverse effects*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011086:Polycythemia / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D006454:Hemoglobins; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I; D004656:Enalapril; D019808:Losartan