title: Increased risk of everolimus-associated acute kidney injury in cancer patients with impaired kidney function.
abstract: BACKGROUND
  Everolimus was recently introduced as a second-line treatment for renal cell carcinoma (RCC) and many other cancers. Several prospective studies have shown that serum creatinine levels are increased in a significant proportion of patients receiving everolimus. However, data on the occurrence of acute kidney injury (AKI) during everolimus treatment in clinical practice are sparse. Here, we report the incidence, risk factors, and clinical significance of AKI associated with everolimus treatment in patients with cancer.
  
  
  METHODS
  We analyzed patients who received everolimus for more than 4 weeks as an anticancer therapy. AKI was defined as increase in creatinine levels from baseline levels greater than 1.5-fold.
  
  
  RESULTS
  The majority of the 110 patients enrolled in this analysis had RCC (N=93, 84.5%). AKI developed in 21 (23%) RCC patients; none of the patients (N=17) with other cancers had AKI. Fourteen of 21 cases were considered to be everolimus-associated AKI, in which there were no other nephrotoxic insults other than everolimus at the onset of AKI. The incidence of AKI increased progressively as baseline estimated glomerular filtration rate (eGFR) decreased (10% in subjects with eGFR >90 mL/min/1.73 m2, 17% in subjects with eGFR 60-90 mL/min/1.73 m2, 28% in subjects with eGFR 30-60 mL/min/1.73 m2, and 100% in subjects with eGFR 15-30 mL/min/1.73 m2; P=0.029 for trend). Baseline eGFR was an independent risk factor for the development of everolimus-associated AKI (hazard ratio per 10 mL/min/1.73 m2 increase, 0.70; 95% confidential interval, 049-1.00; P=0.047). Nine of 14 patients with everolimus-associated AKI continued receiving the drug at a reduced dose or after a short-term off period. Administration of the drug was discontinued in four of 14 patients because of progression of an underlying malignancy. Only one patient stopped taking the drug because of AKI.
  
  
  CONCLUSIONS
  This paper suggests that AKI is a common adverse effect of everolimus treatment, especially in subjects with impaired renal function. However, the occurrence of AKI did not require the discontinuation of the drug, and the treatment decision should be made via a multidisciplinary approach, including the assessment of the oncological benefits of everolimus and other therapeutic options.
authors.forename: Sung Hae
authors.initials: SH
authors.lastname: Ha
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Park
authors.forename: Hye Ryoun
authors.initials: HR
authors.lastname: Jang
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.forename: Ho-Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Yoon-Goo
authors.initials: YG
authors.lastname: Kim
authors.forename: Dae Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Oh
authors.affiliation: Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. jungeun34.lee@samsung.com.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology*; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000503:physiopathology; D003404:Creatinine / Q000097:blood; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D003404:Creatinine; D020123:Sirolimus