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Background The optimal timing to start continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) patients has not been accurately established. The recently proposed risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria for diagnosis and classification of AKI may provide a method for clinicians to decide the optimal timing for starting CRRT under uniform guidelines. The present study aimed: (1) to analyze the correlation between RIFLE stage at the start of CRRT and 90-day survival rate after CRRT start, (2) to further investigate the correlation of RIFLE stage with the malignant kidney outcome in the 90-day survivors, and (3) to determine the influence of the timing of CRRT defined by RIFLE classification on the 90-day survival and malignant kidney outcome in 90-day survivors. Methods A retrospective cohort analysis was performed on the data of 106 critically ill patients with AKI, treated with CRRT during a 6-year period in a university affiliated surgical intensive care unit (SICU). Information such as sex, age, RIFLE stage, sepsis, sepsis-related organ failure assessment (SOFA) score, number of organ failures before CRRT, CRRT time during SiCU, survival, and kidney outcome conditions at 90 days after CRRT start was collected. According to their baseline severity of AKI at the start of CRRT, the patients were assigned to three groups according to the increasing severity of RIFLE stages: RIFLE-R (risk of renal dysfunction, R), RIFLE-I (injury to the kidney, I) and RIFLE-F (failure of kidney function, F) using RIFLE criteria. The malignant kidney outcome was classified as RIFLE-L (loss of kidney function, L) or RIFLE-E (end-stage kidney disease, E) using RIFLE criteria. The correlation between RIFLE stage and 90-day survival rate was analyzed among these three RIFLE-categorized groups. Additionally, the association between RIFLE stage and the malignant kidney outcome (RIFLE-L+RIFLF-E) in the 90-day survivors was analyzed.Results Fifty-three of the overall 106 patients survived to 90 days after the start of CRRT. There were 16, 22 and 68 patients in RIFLE-R, RIFLE-I and RIFLE-F groups respectively with corresponding 90-day survival rate of 75.0% (12/16), 63.6% (14/22) and 39.7% (27/68) (P<0.01, compared among groups). The percentage of the malignant kidney outcome of 90-day survivors in the RIFLE-R, RIFLE-I, and RIFLE-F groups was 16.7% (2/12), 21.4% (3/14) and 55.6% (15/27), respectively (P for trend <0.01). After adjustment for other baseline risk factors, the relative risk (RR) for the 90-day mortality significantly increased with baseline RIFLE stage. Patients in RIFLE-F had a higher RR of 1.96 (95% confidence interval (CI): 1.06-3.62) than patients in RIFLE-I (RR: 1.09, 95% CI: 0.55-2.15) compared with patients in RIFLE-R (P for trend <0.01). Similarly, baseline RIFLE stage also significantly correlated with the odds ratio (OR) for the malignant kidney outcome in 90-day survivors (P for trend <0.05). Ninety-day survivors in the RIFLE-F group had a borderline significantly highest OR of 6.88 (95% CI: 0.85-55.67).Conclusions The RIFLE classification may be used to predict 90-day survival after starting CRRT and the malignant kidney outcome of 90-day survivors in the critically ill patients with AKI treated with CRRT. Starting CRRT prior to RIFLE-F stage may be the optimal timing. Prospective, multi-center, randomized controlled trials are needed to confirm its predictive value in these patients.