title: Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia.
abstract: BACKGROUND
  Monitoring renal function is important in imatinib-treated patients with chronic myeloid leukemia because serum creatinine may increase during the course of therapy. The mechanism of this increase and its reversibility on treatment cessation have never been investigated.
  
  
  METHODS
  We retrospectively analyzed data from imatinib-treated patients explored in our renal physiology unit with measurement of glomerular filtration rate (urinary clearance of (51)CrEDTA) and of urinary clearance and tubular secretion of creatinine. Results were compared with those of controls matched for measured glomerular filtration rate, age, gender, and ethnicity. We also analyzed variations of serum creatinine before and during imatinib cessation and after imatinib resumption in patients enrolled in imatinib discontinuation studies.
  
  
  RESULTS
  In 4 imatinib-treated patients who underwent thorough renal exploration, the part of creatinine clearance due to tubular secretion was negligible (2.4, 3.1, -1.3, and 2.8 mL/min) and significantly lower than that measured in their respective controls (17.7 ± 5.6, 43.0 ± 18.0, 23.1 ± 6.7, and 18.6 ± 5.6 mL/min, P < .001). In 1 patient, exploration was repeated after imatinib discontinuation and evidenced a recovery of creatinine tubular secretion (20.3 vs. 17.9 ± 5.2 mL/min in the control population, P = .2). In 15 patients of imatinib discontinuation studies, a median decrease in serum creatinine of 17.9% was observed after imatinib cessation. Resumption of treatment in 6 patients led to a median increase in serum creatinine of 18.8%.
  
  
  CONCLUSIONS
  Imatinib completely blunts tubular secretion of creatinine, a previously unreported pharmacologic property. This inhibition increases serum creatinine independently of any glomerular dysfunction and is fully reversible on imatinib cessation.
authors.affiliation: Department of Renal Physiology, DHU Fire, Bichat Hospital, AP-HP, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM, U1149, Centre de Recherche sur l'Inflammation, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Vidal-Petiot
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Adult Hematology, Saint-Louis Hospital, AP-HP, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.affiliation: Department of Renal Physiology, DHU Fire, Bichat Hospital, AP-HP, Paris, France.
authors.forename: Fidéline
authors.initials: F
authors.lastname: Serrano
authors.affiliation: Department of Renal Physiology, DHU Fire, Bichat Hospital, AP-HP, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stehlé
authors.affiliation: Department of Hematology, Avicenne Hospital, AP-HP, Bobigny, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Gardin
authors.affiliation: Department of Oncology and Hematology, Hôpital André Mignot, Le Chesnay, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Nephrology, Saint-Louis Hospital, AP-HP, Paris, France.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Peraldi
authors.affiliation: Department of Renal Physiology, DHU Fire, Bichat Hospital, AP-HP, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM, U1149, Centre de Recherche sur l'Inflammation, Paris, France. Electronic address: martin.flamant@aphp.fr.
authors.forename: Martin
authors.initials: M
authors.lastname: Flamant
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood*; D057915:Drug Substitution; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use*; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D003404:Creatinine
keywords: Acute kidney injury; Chronic myeloid leukemia; Creatinine; Glomerular filtration rate; Imatinib; Tubular secretion of creatinine