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. 2019 Dec 31;13(4):660-665.
doi: 10.1093/ckj/sfz183. eCollection 2020 Aug.

Ifosfamide nephrotoxicity in adult patients

Gaël Ensergueix  1 , Nicolas Pallet  1 , Dominique Joly  2 , Charlène Levi  1 , Sophie Chauvet  1 , Claire Trivin  1 , Jean-Francois Augusto  3 , Rémi Boudet  4 , Hail Aboudagga  5 , Guy Touchard  6 , Dominique Nochy  7 , Marie Essig  8 , Eric Thervet  1 , Hélène Lazareth  1 , Alexandre Karras  1
Affiliations

Ifosfamide nephrotoxicity in adult patients

Gaël Ensergueix et al. Clin Kidney J. .

Abstract

Background: Ifosfamide, a widely prescribed antineoplasic agent, is frequently associated with kidney dysfunction. Its nephrotoxicity is well documented in children, but data are lacking in adult patients.

Methods: The aim of this retrospective study was to describe the clinical, biological and histological characteristics of ifosfamide nephrotoxicity.

Results: We report 34 patients (median age: 41 years) admitted in six French nephrology departments for kidney failure and/or tubular dysfunction. Fifteen patients (44.1%) received cisplatin as part of their chemotherapy. In 6 patients (17.7%), ifosfamide nephrotoxicity was revealed by a proximal tubular dysfunction (PTD), in 5 patients (14.4%) by an acute kidney injury (AKI), in 6 patients (17.7%) by a chronic kidney disease (CKD) and in 17 patients (49.7%) by an association of PTD and AKI. Fourteen renal biopsies (41.2%) were performed and revealed acute tubular necrosis (85.7%), vacuolation (78.6%) and nuclear atypias (71.4%) of renal epithelial cells, interstitial inflammation (71.4%) and fibrosis (57.1%). Electron microscopy showed mitochondrial enlargement and dysmorphic changes suggestive of mitochondrial toxicity. Ten patients (29.4%) progressed to Stage 5 CKD, six (17.6%) required haemodialysis and six patients died during a median follow-up period of 31 months. Risk factors for Stage 5 CKD were age and cisplatin co-administration.

Keywords: acute kidney injury; chronic kidney injury; ifosfamide; mitochondrial toxicity; nephrotoxicity; proximal tubular dysfunction.

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Figures

FIGURE 1
FIGURE 1
Masson’s trichrome staining of kidney biopsy showing (A) diffuse tubular denudation at low magnification (scale bar, 250 µm). At higher magnification, Masson’s staining showing (B) denudation of proximal tubular epithelium with loss of brush border (scale bar, 50 µm) and (C) vacuolization of epithelial cells and nuclear atypia (scale bar, 50 µm).
FIGURE 2
FIGURE 2
Representative images of transmission electron microscopy showing (A) enlarged and irregular mitochondria (white stars) and (B) disappearance of mitochondrial ridges (white arrows). Scale bar, 1 µm.
FIGURE 3
FIGURE 3
Comparison of eGFR evolution in patients receiving Ifosfamide or combination of Ifosfamide + Cisplatin using MDRD formula. (A) Global evolution of eGFR at start (D0) and after one, six, twelve months (M1, M6, M12) and at last follow-up (*P < 0.05). (B) Comparison of initial eGFR (D0) and eGFR at last follow-up between patients receiving Ifosfamide or Ifosfamide+cisplatin (*P < 0.05). D0, Day 0; M1, M6, M12, Months 1, 6, 12.
See this image and copyright information in PMC

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