Hematopoietic Stem Cell Mobilization–Associated Granulocytosis Severely Worsens Acute Renal Failure

ABSTRACT. Acute renal failure (ARF), resulting from ischemic or toxic insults, remains a major health care problem because of its grave prognosis and the limited effectiveness of available treatment modalities. On the basis of the recent demonstration that hematopoietic stem cells can differentiate into renal cells and the authors’ observation here that ARF results in a rise in peripheral CD34+ cells, the authors tested whether a further increase in circulating stem cell numbers, induced by their mobilization from the bone marrow, would improve renal function and outcome in mice with ischemic ARF. Unexpected, it was found that the boosting of peripheral stem cell numbers failed to exert any renoprotective effects but rather was associated both with greatly increased severity of renal failure and mortality. Because identical ischemic injury in neutropenic mice resulted in milder renal insufficiency and significantly reduced mortality, it was deduced that the adverse effects of pharmacologic stem cell mobilization are primarily mediated by the concomitant induction of marked granulocytosis. In this manner, high numbers of activated granulocytes seem to obscure the potential renoprotective and positive survival effects of pluripotent hematopoietic stem cells, mediated by both their injurious renal and systemic actions. The data strongly argue against the clinical use of granulocytosis-inducing hematopoietic stem cell mobilization protocols for the prevention or treatment of ischemic ARF. Additional caution with this regimen may be warranted in patients with underlying renal insufficiency and those who develop renal insufficiency while undergoing stem cell mobilization in preparation for an autologous bone marrow transplant.