Impact of Treatment with Imatinib on Renal Histology in Albino Rats

Luma Al-Allaf, Hafidh Al-Ashoo

Abstract


Background: Targeted small molecule drugs have revolutionized treatment of chronic myelogenous
leukemia(CML) over the last decade. however, their use has been found to be associated with serious toxic
effects on a number of vital organs including the kidneys.
Objectives: This study aims to determine the histological changes of the kidney of rats after administration
of a dose of 75mg/kg/once/day of Imatinib mesylate for one month in comparison to control ones.
Study setting and design: This experimental study was conducted on 16 male Albino rats purchased from
Animal Houses of Veterinary College, University of Mosul, Mosul, Northern Iraq.
Methods: In this study a group of eight rats (40- 45 days) were administered orally daily dose of 75mg/Kg/30
days of imatinib mesylate (Glivec®; Novartis). Another group of 8 rats (40- 45 days) were administered
distilled water(D.W) . Kidneys tissues from each rat were obtained. The tissues were embedded in paraffin
and stained with hematoxylin-eosin, periodic acid schiff +Hematoxylin stain, Toluidin blue, and Masson’s
Trichrome.
Results: Rats treated with 75mg/kg /once/day of imatinib for 30 days showed different histological changes
in glomeruli and some parts of the urinary tubules in comparison with controls. The most evident features
are increase in Bowman's space, presence of lobulated or segmented glomeruli, shrunken glomeruli, dilated
tubules with sloughed epithelium, and cloudy degeneration. Congested glomerular capillaries are also
noticed sometimes in these sections with decreased Bowman's space .Dramatic renal injury in these rats was
represented with tubular cell swelling, loss of brush border of proximal convoluted tubules as well as
presence of cloudy degeneration of tubules. In addition, there was a focal accumulation of inflammatory
cells of early inflammation that infiltrate between the tubules at the cortical and corticomedullary portion
and early fibrosis is noticed. Sections obtained from rats treated with imatinib exhibit dilatation and
hyperemia in the intertubular cortical or juxtamedullary blood vessels with appearance of structureless
esinophilic area of necrosis . In addition , dilated tubules with accumulation of eosinophilic homogenous
material in tubular lumen were noticed . The interstitial tissue showed area of hypercellularity, interstitial
oedema and infiltration of mononuclear inflammatory cells (lymphocytes) which tend to be concentrated
around the tubules in the cortical and medullary zones.
Conclusion: Imatinib has adverse effects on the renal histology and results in alterations in the renal cortex
glomerular cells or tubular, which could play an important role in renal dysfunction. A clinical collaboration
between oncologists and nephrologists could be useful with the objective to optimize the management of
tyrosine kinase inhibitors.

Keywords


Imatinib mesylate, chronic myelogenous leukemia, nephrotoxicity, albino rats.

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