Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism by which angiotensin-converting enzyme inhibitors reduce red cell mass in renal transplant recipients with erythrocytosis is unclear. To examine the role of angiotensin II in this disorder, losartan (a competitive antagonist of the angiotensin II type 1 [AT1] receptor) was administered to 23 patients with erythrocytosis. Fourteen patients took 25 mg/d for 8 wk; nine others were treated with 50 mg/d for 8 wk. Hematocrit decreased from 0.527 +/- 0.027 to 0.487 +/- 0.045 after 8 wk (P < 0.01)--by at least 0.04 in 19 patients. Decrement in hematocrit in the initial 8 wk of therapy was significantly greater in patients administered 50 mg/d than in patients on 25 mg/d. Twelve of 14 patients initially treated with 25 mg/d showed a small change in hematocrit; the dose was increased to 50 mg/d for 8 more wk. Hematocrit decreased from 0.528 +/- 0.030 before losartan treatment to 0.483 +/- 0.055 after 16 wk (P < 0.01). After therapy, serum erythropoietin significantly decreased in eight patients with elevated baseline levels, but not in 15 patients with normal baseline levels; however, hematocrit significantly decreased in both groups. Losartan was withdrawn in 16 patients; hematocrit increased from 0.440 +/- 0.057 to 0.495 +/- 0.049 after 8.9 +/- 7.5 wk (P < 0.001), without change in serum erythropoietin. Thus, specific blockade of AT1 receptors inhibited erythropoiesis, suggesting a pathogenic role for angiotensin II in posttransplant erythrocytosis.
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PMID:Losartan, an angiotensin II type 1 receptor antagonist, lowers hematocrit in posttransplant erythrocytosis. 962 Dec 96

Posttransplant erythrocytosis (PTE) is defined as a persistently elevated hematocrit to a level greater than 51% after renal transplantation. It occurs in 10% to 15% of graft recipients and usually develops 8 to 24 months after engraftment. Spontaneous remission of established PTE is observed in one fourth of the patients within 2 years from onset, whereas in the remaining three fourths it persists for several years, only to remit after loss of renal function from rejection. Predisposing factors include male gender, retention of native kidneys, smoking, transplant renal artery stenosis, adequate erythropoiesis prior to transplantation, and rejection-free course with well-functioning renal graft. Just as in other forms of erythrocytosis, a substantial number (approximately 60%) of patients with PTE experience malaise, headache, plethora, lethargy, and dizziness. Thromboembolic events occur in 10% to 30% of the cases; 1% to 2% eventually die of associated complications. Posttransplant erythrocytosis results from the combined trophic effect of multiple and interrelated erythropoietic factors. Among them, endogenous erythropoietin appears to play the central role. Persistent erythropoietin secretion from the diseased and chronically ischemic native kidneys does not conform to the normal feedback regulation, thereby establishing a form of "tertiary hypererythropoietinemia." However, erythropoietin levels in most PTE patients still remain within the "normal range," indicating that erythrocytosis finally ensues by the contributory action of additional growth factors on erythroid progenitors, such as angiotensin II, androgens, and insulin-like growth factor 1 (IGF-1). Inactivation of the renin-angiotensin system (RAS) by an angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin II type 1 AT1 receptor blocker represents the most effective, safe, and well-tolerated therapeutic modality.
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PMID:Posttransplant erythrocytosis. 1263 34