Impaired erythropoietin production in mice treated with cyclosporin A
AM Vannucchi, A Grossi, A Bosi, D Rafanelli, S Guidi, R Saccardi, R Alterini and PR Ferrini
Department of Hematology, Careggi Hospital, Florence, Italy.
Because recent data indicate that erythropoietin (Epo) production is
defective in allogeneic bone marrow transplant (BMT) patients, we
investigated the role of the immunosuppressant, nephrotoxic, agent
cyclosporin A (CsA) on renal Epo production using an animal model. Mice
were injected with 1.0 to 40.0 mg/kg/d CsA for 15 days. Thereafter,
circulating Epo levels were evaluated in both intact animals and in mice
made anemic with phenylhydrazine (PHZ). Serum Epo levels measured in
CsA-treated animals were then compared with the predicted levels, which had
been calculated in a reference population of normal, either intact or
anemic, mice. In CsA-treated, intact animals both hematocrit and serum Epo
levels were not significantly different from controls. However, serum Epo
levels in CsA-treated, anemic mice were significantly lower than those
expected in a control population of untreated, anemic mice with similar
degrees of anemia. No significant increase in serum creatinine was recorded
even at the highest doses of CsA used, nor were we able to document signs
of renal toxicity by histologic examination of the kidneys. Therefore,
therapeutical doses of CsA appear to affect the production of Epo under
conditions in which the demand of the hormone is increased, as in response
to anemia. We suggest that a subclinical kidney toxicity produced by CsA
might have a role in the pathogenesis of the impaired Epo production
observed in BMT patients, and may contribute to a delayed erythroid
engraftment in at least some BMT patients.
Volume 78,
Issue 6,
pp. 1615-1618,
09/15/1991
Copyright © 1991 by The American Society of Hematology
