title: Leukemia kidney infiltration can cause secondary polycythemia by activating hypoxia-inducible factor (HIF) pathway.
abstract: Secondary polycythemia with increased production of erythropoietin (EPO) is known to occur in kidney diseases such as hydronephrosis and cystic disease, but the mechanism remains unclear. We report an 18-year-old female with isolated renal relapse of acute lymphoblastic leukemia accompanied by polycythemia. At the relapse, she presented with bilateral nephromegaly, mild renal dysfunction, and erythrocytosis with increased serum EPO levels up to 52.1 mIU/mL (9.1-32.8). Renal biopsy demonstrated diffuse lymphoblastic infiltration. The expression of hypoxia-inducible factor (HIF)-1α, which is undetectable in normal kidney, was observed in the renal tubule epithelium compressed by lymphoblastic cells. These findings suggest that erythrocytosis was caused by renal ischemia due to leukemic infiltration. Polycythemia probably became apparent because of the lack of leukemic involvement of the bone marrow. With chemotherapy, the serum EPO level rapidly decreased to normal range accompanied by the normalization of kidney size and function. Renal leukemic infiltration may enhance EPO production, although not recognized in the majority of cases because of bone marrow involvement.
  
  
  CONCLUSIONS
  Our case has clarified the mechanism of previously reported polycythemia associated with renal diseases as renal ischemia. Furthermore, we have added renal ischemia resulting from tumor infiltration to the list of causes of secondary polycythemia.
authors.affiliation: Department of Pediatrics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Osumi
authors.forename: Midori
authors.initials: M
authors.lastname: Awazu
authors.forename: Eriko
authors.initials: E
authors.lastname: Fujimura
authors.forename: Fumito
authors.initials: F
authors.lastname: Yamazaki
authors.forename: Akinori
authors.initials: A
authors.lastname: Hashiguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007511:Ischemia / Q000209:etiology* / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D011086:Polycythemia / Q000209:etiology* / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D012008:Recurrence
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit