Clinical Features And Risk Factors Of Cisplatin Induced Acute Kidney Injury In The Elderly Patients

Background and Objectives:The incidence of acute kidney injury(AKI)in the elderly patients appears to be increasing over time.At present,there are few reports about the clinical research of elderly AKI in our country and abroad.The incidence of cancer in the elderly is higher.AKI caused by chemotherapy drugs is rising.Cisplatin is one of the first-line and broad-spectrum antitumor drugs.However,the specific mechanism of nephrotoxicity induced by cisplatin is not clear.And there is still no specific preventive measures.Whether advanced age is a predisposing factor for renal injury induced by platinum drugs is not consistent in the literature.The purpose of this study is to analyze the clinical characteristics and risk factors associated with AKI in the elderly,then analyze the incidence and influencing factors of the elderly AKI induced by cisplatin.At last,we perform a systematic review and meta-analysis about AKI in the elderly with platinum chemotherapy,which will help to guide the clinical prevention and treatment of elderly AKI,reduce the incidence of cisplatin induced AKI,and improve the poor prognosis in elderly AKI.Methods:1.Firstly,we used the patients’ medical records in the database(2009.1.1-2011.12.31)including 15 army hospitals.Eligible patients were aged ≥18 years,diagnosed as AKI using 2012 KDIGO AKI definition(major standard)and the extended standard.Exclusion criteria:Patients with chronic kidney disease stage 5,maintenance dialysis,kidney transplantation,and nephrectomy.To explore the morbidity and mortality of elderly AKI,clinical features and independent risk factors for death of elderly AKI were identified with logistic multivariate regression.2.Secondly,we selected chemotherapeutic patients with cisplatin in Chinese PLA General Hospital from 2013.1.1 to 2015.12.31.Inclusion criteria:patients more than 18 years,diagnosis of primary malignant tumors and the initial use of chemotherapy with cisplatin,having serum creatinine values pre-cisplatin and post-cisplatin 1-2 week’s treatment,with complete medical records.Exclusion criteria:synchronous radiotherapy or surgery before chemotherapy,recurrent malignant tumor,previously used cisplatin,lack of creatinine values before or after cisplatin therapy,lack of admission records or incomplete medical records.The characteristics and risk factors of cisplatin induced AKI in the elderly patients were identified by logistic multivariate regression analysis.3.The literature on the use of platinum drugs in the elderly was searched by the end of December 31,2016.Therefore,a systematic review and meta-analysis were performed to identify the risk of AKI in elderly patients.Results:1.The incidence of AKI in the elderly was 1.61%,and the mortality rate was 16.7%.There were 621,457 patients in the database.Total of 2814 AKI patients were selected,of which 1525 patients were more than 60 years.The average age of the elderly AKI was 73.3±8.2 years,the ratio of male:female was 1.6:1.The comorbidity with hypertension(44.2%vs 31.2%),coronary heart disease(16.1%vs 4.6%)or MODS(20.9%vs 16.9%)was significantly higher in the elderly than that of younger patients,respectively.The length of stay in ICU was more than younger patients.Renal biopsy performance and dialysis treatment was significantly lower in the elderly than in younger AKI patients.The ratio of pre-renal,renal and post-renal AKI in the elderly patients was 58.3%,30.5%,and 12,8%,respectively.52.4%of AKI in the elderly was classified as HA-AKI.The mortality rate of HA-AKI was higher than CA-AKI(20.8%vs 16.6%),and mechanical ventilation treatment was more common(22.5%vs 9.0%,p<0.001).But HA-AKI dialysis patients were less than CA-AKI(10.4%vs 14.8%).The major of AKI was in stage 1 or 2.The mortality rate of AKI increased with the number of organ failure in MODS.3)Aging(OR=1.041,95%CI 1.023,1.059),coronary heart disease(OR=1.98,95%CI,1.402,2.797),tumor(OR=2.302,95%CI 1.654,3.203),multiple organ dysfunction syndrome(MODS)(OR=3.023,95%CI 1.627,5.620),or mechanical ventilation treatment(OR=2.408,95%CI 1.187,4.887)were independent risk factors of death in the elderly AKI.2.The incidence of cisplatin induced AKI in the elderly patients was 9.46%.Total 527 patients from January 1,2013 to December 31,2015 were included in the study,of which 349 were classified to aged group.The average age of elderly patients with cisplatin was 68.25 ± 3.97 years.Male accounted for 79.1%.The comorbidity of hypertension,diabetes,or coronary heart disease were more common in the elderly than in the younger.Cisplatin was administrated by a single dose in 62.4%patients.The average dose of the elderly patients was less than that of the younger(64.32±25.93 vs 69.34±11.22mg/m2).But serum creatinine was higher(73.2± 15.16 vs 68.43±14.60μmol/L).There was no significant difference between the elderly and the younger groups with hydration and diuresis.The average age of AKI in the elderly was 67.45±2.79 years.There was no difference between male and female.There was no difference in the dosage of cisplatin,diuretics,hydration between AKI and non-AKI group in the elderly.However,there were significant differences in serum creatinine,eGFR,ACEI/ARB and single administration of cisplatin.Use of ACEI/ARB drugs(OR=3.398,95%CI 1.352,8.545)and single administration of cisplatin(OR=2.853,95%CI 1.229,6.621)were independent risk factors for cisplatin induced elderly AKI.3.A meta-analysis including 34 literatures showed that risk of elderly AKI induced by platinum drugs was significantly higher than that of younger patients with RR 1.43(95%CI 1.18,1.73).Cisplatin induced AKI in the elderly was significantly higher than that of younger patients,RR 1.42(95%CI 1.16,1.73).The incidence rate of Asian elderly AKI induced by platinum was significantly higher than that of Europe and North America,RR 2.63(95%CI 1.72,4.04).AKI induced by platinum drugs in elderly was gradel/Ⅱ,accounting for 74.8%.Conclusion:1.The incidence and mortality rate of AKI were both higher in the elderly than those in the younger.Eldely AKI patients especially HA-AKI with comorbidity of coronary heart disease or tumor had higher mortality rate.Age,coronary heart disease,tumor,MODS,or mechanical ventilation treatment were independent risk factors for death in elderly AKI.2.The incidence of cisplatin induced AKI in elderly patients was significantly higher than that in the younger.Single administration of cisplatin,combined application of ACEI/ARB drugs were independent risk factors for cisplatin induced AKI in the elderly.3.Cisplatin was the main platinum drug in elderly AKI.