title: Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant.
abstract: Abstract We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal.
authors.affiliation: University of Chicago Pritzker School of Medicine , Chicago, IL , USA.
authors.forename: Camille R
authors.initials: CR
authors.lastname: Petri
authors.forename: Peter H
authors.initials: PH
authors.lastname: O'Donnell
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Cao
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Artz
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.forename: Amittha
authors.initials: A
authors.lastname: Wickrema
authors.forename: Marjie
authors.initials: M
authors.lastname: Hard
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis; D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019540:Area Under Curve; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000077866:Clofarabine; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D000077866:Clofarabine
keywords: Clofarabine; acute kidney injury; glomerular filtration rate; pharmacokinetics