External Validation for Acute Kidney Injury Severity Scores: A Multicenter Retrospective Study in 14 Japanese ICUs.

BACKGROUND/AIMS: Acute kidney injury (AKI) is associated with high mortality. Multiple AKI severity scores have been derived to predict patient outcome. We externally validated new AKI severity scores using the Japanese Society for Physicians and Trainees in Intensive Care (JSEPTIC) database. METHODS: New AKI severity scores published in the 21st century (Mehta, Stuivenberg Hospital Acute Renal Failure (SHARF) II, Program to Improve Care in Acute Renal Disease (PICARD), Vellore and Demirjian), Liano, Simplified Acute Physiology Score (SAPS) II and lactate were compared using the JSEPTIC database that collected retrospectively 343 patients with AKI who required continuous renal replacement therapy (CRRT) in 14 intensive care units. Accuracy of the severity scores was assessed by the area under the receiver-operator characteristic curve (AUROC, discrimination) and Hosmer-Lemeshow test (H-L test, calibration). RESULTS: The median age was 69 years and 65.8% were male. The median SAPS II score was 53 and the hospital mortality was 58.6%. The AUROC curves revealed low discrimination ability of the new AKI severity scores (Mehta 0.65, SHARF II 0.64, PICARD 0.64, Vellore 0.64, Demirjian 0.69), similar to Liano 0.67, SAPS II 0.67 and lactate 0.64. The H-L test also demonstrated that all assessed scores except for Liano had significantly low calibration ability. CONCLUSIONS: Using a multicenter database of AKI patients requiring CRRT, this study externally validated new AKI severity scores. While the Demirjian's score and Liano's score showed a better performance, further research will be required to confirm these findings.

Sepsis may not be a risk factor for mortality in patients with acute kidney injury treated with continuous renal replacement therapy.

PURPOSE: We aimed to study the clinical characteristics, courses, and outcomes of critically ill patients with septic acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) in comparison with nonseptic AKI treated with CRRT. METHODS: This is a multicenter retrospective observational study conducted in 14 Japanese intensive care units in 2010. All adult patients with severe AKI treated with CRRT were eligible (n = 343), and information on patient characteristics, variables at CRRT initiation, CRRT settings, and outcomes was collected. Patients were categorized into the septic AKI group and the nonseptic AKI group according to contributing factors to AKI. RESULTS: Approximately half of study patients (48.7%) had sepsis/septic shock as a contributing factor to AKI, and patients with septic AKI treated with CRRT had more serious clinical conditions than patients with nonseptic AKI. However, no significant difference was observed in intensive care unit mortality (48.5% vs 43.8%; P = .44) and hospital mortality (61.1% vs 56.3%; P = .42) between patients with septic and nonseptic AKIs treated with CRRT. Furthermore, sepsis was associated with lower hospital mortality (odds ratio, 0.378; P = .012) in multivariable regression analysis. CONCLUSION: Sepsis may not be a risk factor for mortality in patients with AKI whose condition has become severe enough to require CRRT.

The lower limit of intensity to control uremia during continuous renal replacement therapy.

INTRODUCTION: The recommended lower limit of intensity during continuous renal replacement therapy (CRRT) is 20 or 25 mL/kg/h. However, limited information is available to support this threshold. We aimed to evaluate the impact of different intensities of CRRT on the clearance of creatinine and urea in critically ill patients with severe acute kidney injury (AKI). METHODS: This is a multicenter retrospective study conducted in 14 Japanese ICUs in 12 centers. All patients older than 18 years and treated with CRRT due to AKI were eligible. We evaluated the effect of CRRT intensity by two different definitions: daily intensity (the mean intensity over each 24-h period) and average intensity (the mean of daily intensity during the period while CRRT was performed). To study the effect of different CRRT intensity on clearance of urea and creatinine, all patients/daily observations were arbitrarily allocated to one of 4 groups based on the average intensity and daily intensity: <10, 10-15, 15-20, and >20 mL/kg/h. RESULTS: Total 316 patients were included and divided into the four groups according to average CRRT intensity. The groups comprised 64 (20.3%), 138 (43.7%), 68 (21.5%), and 46 patients (14.6%), respectively. Decreases in creatinine and urea increased as the average intensity increased over the first 7 days of CRRT. The relative changes of serum creatinine and urea levels remained close to 1 over the 7 days in the "<10" group. Total 1,101 daily observations were included and divided into the four groups according to daily CRRT intensity. The groups comprised 254 (23.1%), 470 (42.7%), 239 (21.7%), and 138 observations (12.5%), respectively. Creatinine and urea increased (negative daily change) only in the "<10" group and decreased with the increasing daily intensity in the other groups. CONCLUSIONS: The lower limit of delivered intensity to control uremia during CRRT was approximately between 10 and 15 mL/kg/h in our cohort. A prescribed intensity of approximately 15 mL/kg/h might be adequate to control uremia for patients with severe AKI in the ICU. However, considering the limitations due to the retrospective nature of this study, prospective studies are required to confirm our findings.

Validity of low-intensity continuous renal replacement therapy*.

OBJECTIVE: To study the hospital mortality of patients with severe acute kidney injury treated with low-intensity continuous renal replacement therapy. DESIGN: Multicenter retrospective observational study (Japanese Society for Physicians and Trainees in Intensive Care), combined with previously conducted multinational prospective observational study (Beginning and Ending Supportive Therapy). SETTING: Fourteen Japanese ICUs in 12 tertiary hospitals (Japanese Society for Physicians and Trainees in Intensive Care) and 54 ICUs in 23 countries (Beginning and Ending Supportive Therapy). PATIENTS: Consecutive adult patients with severe acute kidney injury requiring continuous renal replacement therapy admitted to the participating ICUs in 2010 (Japanese Society for Physicians and Trainees in Intensive Care, n = 343) and 2001 (Beginning and Ending Supportive Therapy Beginning and Ending Supportive Therapy, n = 1,006). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, variables at continuous renal replacement therapy initiation, continuous renal replacement therapy settings, and outcomes (ICU and hospital mortality and renal replacement therapy requirement at hospital discharge) were collected. Continuous renal replacement therapy intensity was arbitrarily classified into seven subclasses: less than 10, 10-15, 15-20, 20-25, 25-30, 30-35, and more than 35 mL/kg/hr. Multivariable logistic regression analysis was conducted to investigate risk factors for hospital mortality. The continuous renal replacement therapy dose in the Japanese Society for Physicians and Trainees in Intensive Care database was less than half of the Beginning and Ending Supportive Therapy database (800 mL/hr vs 2,000 mL/hr, p < 0.001). Even after adjusting for the body weight and dilution factor, continuous renal replacement therapy intensity was statistically different (14.3 mL/kg/hr vs 20.4 mL/kg/hr, p < 0.001). Patients in the Japanese Society for Physicians and Trainees in Intensive Care database had a lower ICU mortality (46.1% vs 55.3%, p = 0.003) and hospital mortality (58.6% vs 64.2%, p = 0.070) compared with patients in the Beginning and Ending Supportive Therapy database. In multivariable regression analysis after combining the two databases, no continuous renal replacement therapy intensity subclasses were found to be statistically different from the reference intensity (20-25 mL/kg/hr). Several sensitivity analyses (patients with sepsis, patients from Western countries in the Beginning and Ending Supportive Therapy database) confirmed no intensity-outcome relationship. CONCLUSIONS: Continuous renal replacement therapy at a mean intensity of 14.3 mL/kg/hr did not have worse outcome compared with 20-25 mL/kg/hr of continuous renal replacement therapy, currently considered the standard intensity. However, our study is insufficient to support the use of low-intensity continuous renal replacement therapy, and more studies are needed to confirm our findings.

Who may not benefit from continuous renal replacement therapy in acute kidney injury?

This study aimed to identify factors that may predict early kidney recovery (less than 48 hours) or early death (within 48 hours) after initiating continuous renal replacement therapy (CRRT) in acute kidney injury (AKI) patients. This is a multicenter retrospective observational study of 14 Japanese Intensive care units (ICUs) in 12 tertiary hospitals. Consecutive adult patients with severe AKI requiring CRRT admitted to the participating ICUs in 2010 (n=343) were included. Patient characteristics, variables at CRRT initiation, settings, and outcomes were collected. Patients were grouped into early kidney recovery group (CRRT discontinuation within 48 hours after initiation, n=52), early death group (death within 48 hours after CRRT initiation, n=52), and the rest as the control group (n=239). The mean duration of CRRT in the early kidney recovery group and early death group was 1.3 and 0.9 days, respectively. In multivariable regression analysis, in comparison with the control group, urine output (mL/h) (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03), duration between ICU admission to CRRT initiation (days) (OR: 0.65, 95% CI: 0.43-0.87), and the sepsis-related organ failure assessment score (OR: 0.87, 95% CI; 0.78-0.96) were related to early kidney recovery. Serum lactate (mmol/L) (OR: 1.19, 95% CI: 1.11-1.28), albumin (g/dL) (OR: 0.52, 95% CI: 0.28-0.92), vasopressor use (OR: 3.68, 95% CI: 1.37-12.16), and neurological disease (OR: 9.64, 96% CI: 1.22-92.95) were related to early death. Identifying AKI patients who do not benefit from CRRT and differentiating such patients from the study cohort may allow previous and future studies to effectively evaluate the indication and role of CRRT.

Low-dose continuous renal replacement therapy for acute kidney injury.

BACKGROUND: Continuous renal replacement therapy (CRRT) is used increasingly to treat acute kidney injury (AKI), which is a common condition in the intensive care unit (ICU). However, the optimal CRRT dose for the treatment of AKI is still a matter of controversy. This study was conducted to ascertain the minimal dose of CRRT that can be effective on AKI patient outcomes. METHODS: This was a retrospective observational study in two ICUs of academic medical centers in Japan. Patients aged 15 years or older admitted to the ICUs from January 2007 to July 2010 and treated with CRRT for AKI during their ICU stay were included. Data were retrospectively collected from patient records. Patients were categorized by doses that were above (higher-dose group) or below (lower-dose group) the median. Major outcome measures were hospital mortality, ICU mortality, and renal recovery at hospital discharge. RESULTS: 131 AKI patients were treated with continuous veno-venous hemodiafiltration (CVVHDF) during the study period. The median dose of CVVHDF was 16 ml/kg per hr (IQR = 14 to 20). Hospital mortality was 44%, which was significantly lower than the predicted mortality (56%, p<0.01). Patients who received lower-dose CRRT tend to have lower mortality rates (36% vs. higher-dose 53%; p = 0.055). CONCLUSIONS: We found that low-dose CRRT did not increase mortality in critically ill patients with AKI. We also found that AKI patients treated with lower-dose CRRT non-significantly but numerically lower hospital mortality compared to higher-dose CRRT.