Respiratory parameters and acute kidney injury in acute respiratory distress syndrome: a causal inference study.

BACKGROUND: Assess the respiratory-related parameters associated with subsequent severe acute kidney injury in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). METHODS: Retrospective cohort, analyzing a large public database-Multiparameter Intelligent Monitoring in Intensive Care-III. Adult patients with at least 48 h of mechanical ventilation (MV), under volume controlled ventilation and an oxygenation index less than 300 mmHg were included. RESULTS: A total of 1,142 patients had complete data and were included in the final analyses. According to a causal directed acyclic graph (DAG) that included respiratory system compliance (Crs), tidal volume (Vt), driving pressure (ΔP), plateau pressure (PPlat), PEEP, PaO2 and PaCO2 as possible exposures related to severe AKI, only Crs and PEEP levels had significant causal association with severe acute kidney injury (AKI) (OR 0.90, 95% CI: 0.84-0.94 for each 5-mL/cmH2O reduction in Crs; OR, 1.05 95% CI: 1.03-1.10 for each 1-cmH2O increase of PEEP). Using mediation analysis, we examined whether any mechanical ventilation, blood gas or hemodynamic parameters could explain the effects of Csr on AKI. Only PEEP mediated the significant but small effect (less than 5%) of Csr on severe AKI. The effects of PEEP, in turn, were not mediated by any other evaluated parameter. Several sensitivity analyses with (I) need of renal replacement therapy (RRT) as an alternative outcome and (II) only patients with Vt <8 mL/kg, confirmed our main findings. In trying to validate our DAG assumptions, we confirmed that only ΔP was associated with mortality but not with severe AKI. CONCLUSIONS: Crs and PEEP are the only respiratory-related variables with a direct causal association in severe AKI. No mechanical ventilator or blood gas parameter mediated the effects of Crs. Approaches reducing Vt and/or ΔP in ARDS can have limited effect on renal protection.

Prediction of 60-Day Case Fatality in Critically Ill Patients Receiving Renal Replacement Therapy: External Validation of a Prediction Model.

BACKGROUND: A recent prognostic model, predicting 60-day case fatality in critically ill patients requiring renal replacement therapy (RRT), has been developed (Acute Renal Failure Trial Network [ATN] study). Because many prognostic models are suggested in literature, but just a few have found its way into clinical practice, we aimed to externally validate this prediction model in an independent cohort. METHODS: A total of 1,053 critically ill patients requiring RRT from the MIMIC-III database were analyzed. The models' discrimination was evaluated using c-statistics. Calibration was evaluated by Hosmer-Lemeshow (H-L) test and GiViTi calibration belt. RESULTS: In a case-mix population, including patients with normal or altered serum creatinine (sCr) at intensive care unit admission, discrimination was moderate, with a c-statistic of 0.71 in the nonintegerized risk model. In patients with altered baseline sCr, better discrimination was achieved with the integer risk model (0.76, 95% confidence interval, 0.71-0.81). As for the calibration, although the H-L test was good only in patients with normal/slightly altered sCr at admission, the calibration belt disclosed no significant deviations from the bisector line for any of the models in patients, regardless of admission sCr. Of note, a refitted model had a c-statistics of 0.85, similar to the derivation cohort. CONCLUSIONS: The ATN prognostic model can be useful in a broad cohort of critically ill patients. Although it showed only moderate discrimination capacity when patients with elevated admission sCr were included, using a refitted model improved it, illustrating the need for continuous external validation and updating of prognostic models over time before their implementation in clinical practice.

Quantitative Renal Echogenicity as a Tool for Diagnosis of Advanced Chronic Kidney Disease in Patients with Glomerulopathies and no Liver Disease.

BACKGROUND/AIMS: Glomerulopathy patients are prone to developing transitory reduced glomerular filtration rate (GFR), which can be difficult to differentiate from irreversible chronic kidney disease (CKD). Renal ultrasound can be useful, but differently from renal length, quantitative renal echogenicity has not been formerly evaluated regarding its capacity to identify irreversible advanced CKD. METHODS: A prospective study was performed, where quantitative renal echogenicity was performed during renal biopsy in patients with suspected glomerular disease (n=197). Quantitative echogenicity was measured as the inverse of the ratio between the mean pixel densities of the renal cortex and adjacent liver using ScionImage software. Patients were followed during a six-months period to ascertain irreversible advanced CKD. Quantitative renal echogenicity and histopathology parameters discriminatory capacity were compared regarding their capacity to detect advanced and irreversible CKD - estimated GFR less than 30mL/min/1.73m2 confirmed after a six-month follow-up. RESULTS: At renal biopsy, the mean eGFR was 53.9±33.6 mL/min/1.73m2 and 63 (32.0%) patients had an eGFR less than 30 mL/min/1.73m2. Mean kidney/liver echogenicity ratio was 1.06±0.19 and it was inversely correlated with eGFR at follow-up (r=-0.684, p<0.001). Multivariate analysis was performed to create a histopathology index that correctly identifies irreversible advanced CKD. Renal echogenicity discriminatory capacity to identify irreversible advanced CKD was 0.793 (0.719 -0.867), similar to the histopathology index. Elevated renal echogenicity with best discriminatory capacity was a kidney/liver ratio greater than 1.15. This cutoff had a predictive positive value of 92% in patients with eGFR less than 30mL/min/1.73m2. CONCLUSION: Quantitative renal echogenicity can be a useful tool in patients with glomerular disease and normal kidney size (>8cm) to identify those patients with irreversible advanced CKD.

Polymyxin-B and vancomycin-associated acute kidney injury in critically ill patients.

BACKGROUND: This study aims to investigate renal toxicities of Polymyxin B and Vancomycin among critically ill patients and risk factors for acute kidney injury (AKI). METHODS: This is a cross-sectional study conducted with patients admitted to an intensive care unit (ICU) of a tertiary hospital in Brazil. Patients were divided into two groups: those who used association of Polymyxin B + Vancomycin (Group I) and those who used only Polymyxin B (Group II). Risk factors for AKI were also analyzed. RESULTS: A total of 115 patients were included. Mean age was 59.2 ± 16.1 years, and 52.2% were males. Group I presented higher GFR (117.1 ± 70.5 vs. 91.5 ± 50 ml/min/1.73 m², p = 0.02) as well as lower creatinine (0.9 ± 0.82 vs. 1.0 ± 0.59 mg/dL, p = 0.014) and urea (51.8 ± 23.7 vs. 94.5 ± 4.9 mg/dL, p = 0.006) than group II on admission. Group I also manifested significantly higher incidence of AKI than group II (62.7% vs. 28.5%, p = 0.005), even when stratified according to RIFLE criteria ('Risk' 33.9% vs. 10.7%; 'Injury' 10.2% vs. 8.9%; 'Failure' 18.6% vs. 8.9%; p = 0.03). Accumulated Polymyxin B dose > 10 million IU was an independent predictor for AKI (OR = 2.72, 95% CI = 1.13-6.51, p = 0.024). CONCLUSIONS: Although patients who received Polymyxin B plus vancomycin had more favorable clinical profile and higher previous GFR, they presented a higher AKI incidence than those patients who received Polymyxin B alone. Cumulative Polymyxin B dose > 10 million IU was independently associated to AKI.

Hyponatremia and risk factors for death in human visceral leishmaniasis: new insights from a cross-sectional study in Brazil.

BACKGROUND: Visceral leishmaniasis (VL) is an important and potentially fatal neglected tropical disease. The aim of this study was to investigate hyponatremia and risk factors for death among VL patients. METHODS: This is a cross-sectional study with VL patients admitted to a tertiary hospital in Northeast Brazil, from 2002 to 2009. Patients were divided into two groups: non-survivors and survivors. Hyponatremia was defined as serum sodium < 135 mEq/L. A logistic regression model was done to investigate risk factors for death. RESULTS: A total of 285 VL patients were included, with mean age 37 ± 15 years, and 74% were males. Thirty-four patients died (11.9%). Non-survivors had a significantly higher prevalence of dyspnea (38.2 vs. 16.7%, p = 0.003), pulmonary crackles (11.8 vs. 4.0%, p = 0.049), dehydration (23.5 vs. 10.8%, p = 0.033), oliguria (8.8 vs. 0.8%, p = 0.001) and jaundice (47.1 vs. 14.3%, p < 0.001). They also presented higher prevalence of hyponatremia (41.9 vs. 24.1%, p = 0.035), thrombocytopenia (91.2 vs. 65.3%, p = 0.002) and severe hypoalbuminemia (78.3 vs. 35.3%, p < 0.001). In multivariate analysis, moderate/severe hyponatremia (OR = 2.278, 95% CI = 1.046-4.962), thrombocytopenia (OR = 5.482, 95% CI = 1.629-18.443), jaundice (OR = 5.133, 95% CI = 1.793-14.696) and severe hypoalbuminemia (OR = 6.479, 95% CI = 2.124-19.766) were predictors of death. CONCLUSION: Higher prevalence of dehydration, oliguria, pulmonary symptoms and liver involvement was found in non-survivors VL patients. Hypoalbuminemia and hyponatremia were frequent and significantly associated with mortality.

Renal Outcomes in Critically Ill Patients Receiving Propofol or Midazolam.

BACKGROUND AND OBJECTIVES: Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is limited to patients undergoing cardiac surgery. There are no data about its association with oliguria and AKI in critically ill patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We obtained data from the Multiparameter Intelligent Monitoring in Intensive Care II database (2001-2008). Patient selection criteria included adult patients in their first intensive care unit (ICU) admission, need for mechanical ventilation, and treatment with propofol or midazolam. Propensity score analysis (1:1) was used and renal-related outcomes (AKI, oliguria, cumulative fluid balance, and need for RRT) were evaluated during the first 7 days of ICU stay. RESULTS: There were 1396 propofol/midazolam-matched patients. AKI in the first 7-day ICU time period was statistically lower in propofol-treated patients compared with midazolam-treated patients (55.0% versus 67.3%, P<0.001). Propofol was associated with lower AKI incidence using both urine output (45.0% versus 55.7%, P<0.001) and serum creatinine criteria (28.8% versus 37.2%, P=0.001). Patients receiving propofol had oliguria (<400 ml/d) less frequently (12.4% versus 19.6%, P=0.001) and had diuretics prescribed less often (8.5% versus 14.3%, P=0.001). In addition, during the first 7 days of ICU stay, patients receiving propofol less frequently achieved cumulative fluid balance >5% of body weight (50.1% versus 58.3%, P=0.01). The need for RRT in the first 7 days of ICU stay was also less frequent in propofol-treated patients (3.4% versus 5.9%, P=0.03). ICU mortality was lower in propofol-treated patients (14.6% versus 29.7%, P<0.001). CONCLUSIONS: In this large, propensity-matched ICU population, patients treated with propofol had a lower risk of AKI, fluid-related complications, and need for RRT.

Increased serum bicarbonate in critically ill patients: a retrospective analysis.

PURPOSE: Although metabolic alkalosis is a common occurrence, no study has evaluated its prevalence, associated factors or outcomes in critically ill patients. METHODS: This is a retrospective study from the Multiparameter Intelligent Monitoring in Intensive Care II database. From 23,529 adult patient records, 18,982 patients met the inclusion criteria. RESULTS: Serum bicarbonate levels demonstrated a U-shaped association with mortality with knots at 25 and 30 mEq/l. Of the total included patients, 5,565 (29.3 %) had at least one serum bicarbonate level measurement >30 mEq/l. The majority were exposed to multiple factors that are classically associated with metabolic alkalosis (mainly diuretic use, hypernatremia, hypokalemia and high gastric output). Patients with increased serum bicarbonate exhibited increased ICU LOS, more days on mechanical ventilation and higher hospital mortality. After multivariate adjustment, each 5-mEq/l increment in the serum bicarbonate level above 30 mEq/l was associated with an odds ratio of 1.21 for hospital mortality. The association between increased serum bicarbonate levels and mortality occurs independently of its possible etiologies. CONCLUSION: An increased serum bicarbonate level is common in critically ill patients; this can be attributed to multiple factors in the majority of cases, and its presence and duration negatively influence patient outcomes.

AKI complications in critically ill patients: association with mortality rates and RRT.

BACKGROUND AND OBJECTIVES: AKI is associated with short- and long-term mortality. However, the exact contribution of AKI complications to the burden of mortality and whether RRT has any beneficial effect on reducing mortality rates in critically ill AKI patients are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective analysis using data from the Multiparameter Intelligent Monitoring in Intensive Care II project. A total of 18,410 adult patients were enrolled from four intensive care units from a university hospital from 2001 to 2008. RESULTS: Overall, 10,245 patients developed AKI. After adjustments, the odds ratios (ORs) for hospital mortality were 1.73 (95% confidence interval [95% CI], 1.52 to 1.98) for AKI stage 1, 1.88 (95% CI, 1.57 to 2.25) for stage 2, and 2.89 (95% CI, 2.41 to 3.46) for stage 3. Totals of 33%, 59%, and 70% of the excess mortality rates associated with AKI stages 1, 2, and 3, respectively, were attenuated by the inclusion of each AKI-related complication in the model. The main burden of excess hospital mortality associated with AKI was attenuated by metabolic acidosis and cumulative fluid balance. Long-term mortality was not attenuated by any of the associated complications. Next, we used two different approaches to explore the associations between RRT, AKI complications, and hospital mortality: multivariate analysis and propensity score matching. In both approaches, the sensitivity analysis for RRT was associated with a better hospital survival in only the following AKI-related subgroups: hyperkalemia (OR, 0.55; 95% CI, 0.35 to 0.85), metabolic acidosis (OR, 0.70; 95% CI, 0.53 to 0.92), cumulative fluid balance >5% of body weight (OR, 0.60; 95% CI, 0.40 to 0.88), and azotemia (OR, 0.57; 95% CI, 0.40 to 0.81). CONCLUSIONS: A majority of the excess risk of mortality associated with AKI was attenuated by its fluid volume and metabolic complications, particularly in severe AKI. In addition, this study demonstrated that RRT is associated with a better outcome in patients with AKI-related complications.

Kidney Disease Improving Global Outcomes or creatinine kinetics criteria in acute kidney injury: a proof of concept study.

BACKGROUND: It has been recently mathematically demonstrated that the percentage increase in serum creatinine (SCr) can delay acute kidney injury (AKI) diagnosis in patients with previous chronic kidney disease (CKD). Based on creatinine (Cr) kinetics, it was suggested a new AKI classification using absolute increase in SCr elevation over specified time periods. However, this classification has not been evaluated in clinical studies. METHODS: A prospective cohort study evaluated myocardial infarction patients during the first 7 days of hospital stay with daily SCr measurements. They were classified using Kidney Disease Improving Global Outcomes (KDIGO) and Cr kinetics systems. Both classifications were compared by net reclassification improvement (NRI) and area under the receiver operator characteristic (AuROC) curve regarding hospital mortality. RESULTS: A total of 584 patients were included, of which 34.1% had previous CKD. Patients had more AKI by KDIGO than by Cr kinetics criteria (25.7 versus 18.0%, P < 0.001) and 81 patients (13.9%) had different AKI severity classification. Patients with AKI by KDIGO criteria and non-AKI by Cr kinetics had higher hospital mortality rates than patients with non-AKI using both classifications [adjusted mortality odds ratios (ORs): 4.753; 95% confidence interval (CI): 1.119-9.023, P = 0.014]. In patients with previous CKD, NRI analysis was 6.2% favoring Cr kinetics criteria. However, there was no difference using the AuROC curve analysis. In patients with no previous CKD, NRI analysis was 33.0%, favoring KDIGO, and this was in accordance with a better AuROC curve (0.828 versus 0.664, P < 0.05). CONCLUSIONS: AKI classification proposed by a Cr kinetics model can be superior when diagnosing patients with previous CKD. However, KDIGO had a better performance in patients with no previous CKD.