Tetsu Ohnuma

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.

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.

Utility of the Penn Classification in Predicting Outcomes of Surgery for Acute Type A Aortic Dissection

The Penn classification, a risk assessment system for acute type A aortic dissection (AAAD), is based on preoperative ischemic conditions. We investigated whether Penn classes predict outcomes after surgery for AAAD. Three hundred fifty-one patients with DeBakey type I AAAD treated surgically, January 1997 to January 2011, were divided into 4 groups per Penn class: Aa (no ischemia, n = 187), Ab (localized ischemia with branch malperfusion, n = 67), Ac (generalized ischemia with circulatory collapse, n = 46), and Abc (localized and generalized ischemia, n = 51). Early and late outcomes were compared between groups. In-hospital mortality was 3% (6 of 187) for Penn Aa, 6% (4 of 67) for Penn Ab, 17% (8 of 46) for Penn Ac, and 22% (11 of 51) for Penn Abc. Multivariate logistic regression analysis showed Penn classes Ac and Abc, operation time >6 hours, and entry in the descending thoracic aorta to be risk factors for in-hospital mortality. Incidences of neurologic, respiratory, and hepatic complications differed between groups. Five-year cumulative survival was 85% in the Penn Aa group, 74% in the Penn Ab group (p = 0.027 vs Penn Aa), 78% in the Penn Ac group, and 67% in the Penn Abc group (p <0.001 vs Penn Aa). In conclusion, morbidity and mortality are high in patients with generalized ischemia. The Penn classification appears to be a useful risk assessment system for AAAD, predictive of outcomes.

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

IntroductionThe 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).MethodsThis 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.ResultsTotal 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.ConclusionsThe 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.

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 Demirjians score and Lianos score showed a better performance, further research will be required to confirm these findings.

Prediction Models and Their External Validation Studies for Mortality of Patients with Acute Kidney Injury: A Systematic Review.

Objectives To systematically review AKI outcome prediction models and their external validation studies, to describe the discrepancy of reported accuracy between the results of internal and external validations, and to identify variables frequently included in the prediction models. Methods We searched the MEDLINE and Web of Science electronic databases (until January 2016). Studies were eligible if they derived a model to predict mortality of AKI patients or externally validated at least one of the prediction models, and presented area under the receiver-operator characteristic curves (AUROC) to assess model discrimination. Studies were excluded if they described only results of logistic regression without reporting a scoring system, or if a prediction model was generated from a specific cohort. Results A total of 2204 potentially relevant articles were found and screened, of which 12 articles reporting original prediction models for hospital mortality in AKI patients and nine articles assessing external validation were selected. Among the 21 studies for AKI prediction models and their external validation, 12 were single-center (57%), and only three included more than 1,000 patients (14%). The definition of AKI was not uniform and none used recently published consensus criteria for AKI. Although good performance was reported in their internal validation, most of the prediction models had poor discrimination with an AUROC below 0.7 in the external validation studies. There were 10 common non-renal variables that were reported in more than three prediction models: mechanical ventilation, age, gender, hypotension, liver failure, oliguria, sepsis/septic shock, low albumin, consciousness and low platelet count. Conclusions Information in this systematic review should be useful for future prediction model derivation by providing potential candidate predictors, and for future external validation by listing up the published prediction models.

Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery–associated acute kidney injury: A multicenter randomized controlled trial

Purpose: To evaluate the effects of atrial natriuretic peptide (ANP) on renal function and medical costs in patients with acute kidney injury (AKI) associated with cardiac surgery. Materials and methods: The Japanese trial for AKI in Post‐cardiovascular surgery patients by ANP (JAPAN) was a prospective, multicenter, randomized, double‐blind, placebo‐controlled study conducted in 11 hospitals in Japan. Acute kidney injury was defined as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours. The patients were randomly assigned to receive ANP (0.02 &mgr;g kg−1 min−1) or placebo. The primary end point was a change in renal function. The secondary end points were a need for renal replacement therapy, the lengths of intensive care unit and hospital stays, and medical costs incurred over the 90‐day follow‐up. Results: Of the 77 randomized patients, 37 were in the ANP group and 40 were in the placebo group. Although ANP significantly (P = .018) increased urine output, it did not significantly improve renal function compared with placebo. There were no significant differences between the groups in the renal replacement therapy rate, the lengths of the intensive care unit and hospital stays, or medical costs. Conclusion: Atrial natriuretic peptide infusion did not show a renoprotective effect or cost‐saving effect in the treatment of cardiac surgery–associated AKI. HighlightsANP was administered in patients with AKI associated with cardiac surgery.ANP significantly increased urine output.ANP did not significantly improve renal function.ANP did not significantly reduce the renal replacement therapy rate or medical costs.

Physician attire in the intensive care unit in Japan influences visitors' perception of care

Purpose: The objective of this study is to evaluate the impact of physician attire and behavior on perceptions of care by ICU visitors in Japan. Materials and methods: Visitors were surveyed including 117 at a community hospital and 106 at a university hospital. Demographic data (age, gender, relationship to patient, length of stay) were collected. A seven‐point Likert scale (1 = strongly agree, 4 = neutral, 7 = strongly disagree) was used to judge physician attire (name tag, white coat, scrubs, short sleeve shirts, blue jeans, sneakers, clogs), behavior (addressing a patient, carrying a snack) and overall effect on perception of care. Results: There are no significant differences (p > 0.05) in demographics comparing the two ICUs, except for increased length of stay at the university ICU. Visitors scored the importance of a name tag (median 2, Interquartile Range 1–2), white coat [3,1–4], addressing the patient by last name [2,1–3], wearing scrubs [3,2–4], sneakers [4,3–5], clogs [4,4–5], short sleeves (4,3.5–5), blue jeans [5,4–6], and carrying a snack [6,5–7]. Visitors scored “attire affects perceptions of care” as [3,2–4]. Conclusions: Physician attire in the ICU affects perceptions of care. Implementation of attire guidelines which require clothing that does not meet visitor preferences should be accompanied by education programs. Highlights:Physician attire affects perceptions of care, but there are few studies in the intensive care unit (ICU), or from Japan.A majority of ICU visitors agree that doctors should wear a name tag, white coat and address patients by last name. A majority disagree that wearing blue jeans and carrying a snack is acceptable.As guidelines for attire are implemented to reduce nosocomial infections, preferences of patients and family must be considered.