title: Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study.
abstract: Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin-associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients.
authors.affiliation: Wayne State University, School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Zeenat Yousuf
authors.initials: ZY
authors.lastname: Bhat
authors.affiliation: Wayne State University, School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Pravit
authors.initials: P
authors.lastname: Cadnapaphornchai
authors.affiliation: Wayne State University, School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ginsburg
authors.affiliation: Wayne State University, School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Milani
authors.initials: M
authors.lastname: Sivagnanam
authors.affiliation: Patel Hospital, Civil Lines, Jalandhar City, Punjab, India.
authors.forename: Shamit
authors.initials: S
authors.lastname: Chopra
authors.affiliation: Cass Street, Ear, Nose & Throat Associates, Traverse City, Michigan, United States of America.
authors.forename: Corey K
authors.initials: CK
authors.lastname: Treadway
authors.affiliation: Wayne State University, School of Medicine, Detroit, Michigan, United States of America.|Karmanos Cancer Institute, Detroit, Michigan, United States of America.
authors.forename: Ho-Sheng
authors.initials: HS
authors.lastname: Lin
authors.affiliation: Wayne State University, School of Medicine, Detroit, Michigan, United States of America.|Karmanos Cancer Institute, Detroit, Michigan, United States of America.
authors.forename: George
authors.initials: G
authors.lastname: Yoo
authors.affiliation: Wayne State University, School of Medicine, Detroit, Michigan, United States of America.|Karmanos Cancer Institute, Detroit, Michigan, United States of America.
authors.forename: Ammar
authors.initials: A
authors.lastname: Sukari
authors.affiliation: Wayne State University, School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Mona D
authors.initials: MD
authors.lastname: Doshi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000401:mortality; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D003404:Creatinine; D002945:Cisplatin