Leukemia kidney infiltration can cause secondary polycythemia by activating hypoxia-inducible factor (HIF) pathway

Tomoo Osumi, Midori Awazu, Eriko Fujimura, Fumito Yamazaki, Akinori Hashiguchi, Hiroyuki Shimada

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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. C onclusion: 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.

Original languageEnglish
Pages (from-to)829-832
Number of pages4
JournalEuropean Journal of Pediatrics
Issue number6
Publication statusPublished - 2013 Jun


  • Acute lymphoblastic leukemia
  • Erythropoietin
  • HIF-1α
  • Renal ischemia
  • Secondary polycythemia

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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