Urine biochemistry in septic and non-septic acute kidney injury: a prospective observational study

Purpose

Determine whether there are unique patterns to the urine biochemistry profile in septic compared with non-septic acute kidney injury (AKI) and whether urinary biochemistry predicts worsening AKI, need for renal replacement therapy and mortality.

Materials and Methods

Prospective cohort study of critically ill patients with septic and non-septic AKI, defined by the RIFLE (Risk, Injury, Failure, Loss, End-Stage) criteria. Urine biochemistry parameters were compared between septic and non-septic AKI and were correlated with neutrophil gelatinase-associated lipocalin (NGAL), worsening AKI, renal replacement therapy (RRT), and mortality.

Results

Eighty-three patients were enrolled, 43 (51.8%) with sepsis. RIFLE class was not different between groups (P = .43). Urine sodium (UNa) < 20 mmol/L, fractional excretion of sodium (FeNa) < 1%, and fractional excretion of urea (FeU) < 35% were observed in 25.3%, 57.8%, and 33.7%, respectively. Septic AKI had lower UNa compared with non-septic AKI (P = .04). There were no differences in FeNa or FeU between groups. Urine NGAL was higher for FeNa≥1% compared to FeNa<1% (177.4 ng/mL [31.9-956.5] vs 48.0 ng/mL [21.1-232.4], P = .04). FeNa showed low correlation with urine NGAL (P = .05) and plasma NGAL (P = .14). There was poor correlation between FeU and urine NGAL (P = .70) or plasma NGAL (P = .41). UNa, FeNa, and FeU showed poor discrimination for worsening AKI, RRT and mortality.

Conclusion

Urine biochemical profiles do not discriminate septic and non-septic AKI. UNa, FeNa, and FeU do not reliably predict biomarker release, worsening AKI, RRT or mortality. These data imply limited utility for these measures in clinical practice in critically ill patients with AKI.     

Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies

Purpose  

To test the hypothesis that hypoalbuminemia is independently associated with increased risk of acute kidney injury (AKI).     

Evaluation of urinary tissue inhibitor of metalloproteinase-2 in acute kidney injury: a prospective observational study

Introduction

Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an emerging acute kidney injury (AKI) biomarker. We evaluated the performance of urinary TIMP-2 in an adult mixed ICU by comparison with other biomarkers that reflect several different pathways of AKI.

Methods

In this study, we prospectively enrolled 98 adult critically ill patients who had been admitted to the adult mixed ICU. Urinary TIMP-2 and N-acetyl-β-d-glucosaminidase (NAG) and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6) and erythropoietin (EPO) were measured on ICU admission. We evaluated these biomarkers’ capability of detecting AKI and its severity as determined by using the Kidney Disease Improving Global Outcomes serum creatinine criteria, as well as its capacity to predict in-hospital mortality. The impact of sepsis, the leading cause of AKI in ICUs, was also evaluated.

Results

We found AKI in 42 patients (42.9%). All biomarkers were significantly higher in AKI than in non-AKI. In total, 27 patients (27.6%) developed severe AKI. Urinary TIMP-2 was able to distinguish severe AKI from non-severe AKI with an area under the receiver operating characteristic curve (AUC-ROC) of 0.80 (95% confidence interval, 0.66 to 0.90). A total of 41 cases (41.8%) were complicated with sepsis. Although plasma NGAL and IL-6 were increased by sepsis, urinary TIMP-2 and NAG were increased not by sepsis, but by the presence of severe AKI. Plasma EPO was increased only by septic AKI. In-hospital mortality was 15.3% in this cohort. Urinary TIMP-2 and NAG, and plasma NGAL, were significantly higher in non-survivors than in survivors, although plasma IL-6 and EPO were not. Among the biomarkers, only urinary TIMP-2 was able to predict in-hospital mortality significantly better than serum creatinine.

Conclusion

Urinary TIMP-2 can detect severe AKI with performance equivalent to plasma NGAL and urinary NAG, with an AUC-ROC value higher than 0.80. Furthermore, urinary TIMP-2 was associated with mortality. Sepsis appeared to have only a limited impact on urinary TIMP-2, in contrast to plasma NGAL.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0716-5) contains supplementary material, which is available to authorized users.     

Urinary interleukin-18 does not predict acute kidney injury after adult cardiac surgery: a prospective observational cohort study

Introduction  

Urinary interleukin-18 (IL-18) measured during the immediate postoperative period could be a promising predictor of acute kidney injury following adult cardiac surgery.     

Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study

Introduction  

Antibiotic de-escalation, which consists of the initial institution of empiric broad-spectrum antibiotics followed by antibiotic streamlining driven by microbiological documentation, is thought to provide maximum benefit for the individual patient, while reducing the selection pressure for resistance.     

Six-month outcome in acute kidney injury requiring renal replacement therapy in the ICU: a multicentre prospective study

Objective  

To assess quality of life (QOL), mortality rate and renal function 6 months after onset of renal replacement therapy (RRT) for acute kidney injury (AKI) in the ICU.     

Whole-blood neutrophil gelatinase-associated lipocalin to predict adverse events in acute kidney injury: A prospective observational cohort study

PurposeAcute kidney injury is common in intensive care units and is associated with increased morbidity and mortality. We evaluated the ability of whole-blood neutrophil gelatinase-associated lipocalin (wbNGAL) to predict mortality and need for renal replacement therapy (RRT) in critically ill patients with kidney dysfunction.MethodsWe prospectively enrolled adult patients in 5 Canadian intensive care units. We measured wbNGAL at the time of enrollment to determine whether NGAL concentration could predict the primary composite outcome of death or need for RRT by day 30 in addition to other secondary outcomes.ResultsWe recruited 234 patients; 227 were included in the analysis. In a multivariable model, wbNGAL did not predict 30-day mortality or need for RRT (odds ratio, 1.05; 95% confidence interval, 0.99-1.12). Neutrophil gelatinase-associated lipocalin was similar in patients who died (654 [303-1180] ng/mL) vs those who survived (541.5 [255.5-1080] ng/mL, P = .26) by 90 days. Whole-blood NGAL poorly predicted the primary outcome (area under receiver operator curve, 0.65; 95% confidence interval, 0.58-0.73).ConclusionsIn a cohort of critically ill patients with abnormal kidney function, wbNGAL was not effective in the prediction of death or RRT within 30 days. These data do not support the use of this biomarker for the detection of clinical outcomes in this population.     

The impacts of thyroid function on the diagnostic accuracy of Cystatin C to detect acute kidney injury in ICU patients: a prospective,observational study

Introduction

Cystatin C (Cysc) could be affected by thyroid function both in vivo and in vitro and thereby may have limited ability to reflect renal function. We aimed to assess the association between Cysc and thyroid hormones as well as the effect of thyroid function on the diagnostic accuracy of Cysc to detect acute kidney injury (AKI).

Methods

A total of 446 consecutive intensive care unit (ICU) patients were screened for eligibility in this prospective AKI observational study. Serum Cysc, thyroid hormones and serum creatinine (Scr) were measured upon entry to the ICU. We also collected each patient''s baseline characteristics including the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. The diagnostic performance of Cysc was assessed from the area under the receiver operator characteristic curve (AUC) in each quartile of thyroid hormone(s).

Results

A total of 114 (25.6%) patients had a clinical diagnosis of AKI upon entry to the ICU. The range of free thyroxine (FT4) value was 4.77 to 39.57 pmol/L. Multivariate linear regression showed that age (standardized beta = 0.128, P < 0.0001), baseline Scr level (standardized beta = 0.290, P < 0.0001), current Scr (standardized beta = 0.453, P < 0.0001), albumin (standardized beta = -0.086, P = 0.006), and FT4 (standardized beta = 0.062, P = 0.039) were related with Cysc. Patients were divided into four quartiles based on FT4 levels. The AUC for Cysc in detecting AKI in each quartile were as follows: 0.712 in quartile I, 0.754 in quartile II, 0.829 in quartile III and 0.797 in quartile IV. There was no significant difference in the AUC between any two groups (all P > 0.05). The optimal cut-off value of Cysc for diagnosing AKI increased across FT4 quartiles (1.15 mg/L in quartile I, 1.15 mg/L in quartile II, 1.35 mg/L in quartile III and 1.45 mg/L in quartile IV).

Conclusions

There was no significant impact of thyroid function on the diagnostic accuracy of Cysc to detect AKI in ICU patients. However, the optimal cut-off value of Cysc to detect AKI could be affected by thyroid function.     

NGAL、KIM-1、TIMP-2对脓毒症所致AKI早期诊断价值的前瞻性临床队列研究

目的评估血浆中性粒细胞明胶酶相关载脂蛋白（pNGAL）、尿中性粒细胞明胶酶相关载脂蛋白（uNGAL）、尿肾损伤分子-1（KIM-1）和尿金属蛋白酶抑制物-2（TIMP-2）对脓毒症急性肾损伤（AKI）的早期诊断价值。 方法收集2015年6月至2016年1月期间入住苏北人民医院重症医学科（ICU）的脓毒症患者,连续观察72 h,以是否出现AKI进行分组,即脓毒症AKI组及脓毒症非AKI组,收集各组患者的一般资料,入ICU时（0 h）,入ICU后6、12、24、48、72 h时的外周静脉血及尿液样本,并采用酶联免疫吸附试验（ELISA）测定各时刻pNGAL、uNGAL、尿KIM-1、尿TIMP-2的表达水平,绘制受试者工作特征（ROC）曲线,计算曲线下面积（AUC）,评价pNGAL、uNGAL、尿KIM-1、尿TIMP-2对脓毒症AKI的早期诊断价值。 结果研究期间共有522例患者入住我院ICU,最终纳入符合研究标准的脓毒症患者共90例,其中38例发生AKI,占42.22%。脓毒症AKI组患者pNGAL、uNGAL水平在入住ICU后6 h开始升高（P<0.05）,12 h开始明显升高,24 h达到峰值,在6、12、24、48、72 h时pNGAL浓度明显高于同时刻脓毒症非AKI组患者,差异具有统计学意义（P<0.05）。脓毒症AKI组患者尿KIM-1、尿TIMP-2水平在入住ICU后6 h开始升高（P<0.05）,12 h开始明显升高并达到峰值,在6、12、24、48、72 h时尿KIM-1水平明显高于同时刻脓毒症非AKI组患者,差异具有统计学意义（P<0.05）。ROC曲线显示pNGAL、uNGAL、尿KIM-1、尿TIMP-2的ROC的AUC分别为0.862、0.858、0.788、0.771,其诊断截断值分别为119.30、120.36、90.07、3299.50 ng/L。各时间点绘制ROC曲线显示,在T-12 h时,pNGAL、尿KIM-1及尿TIMP-2的ROC的AUC分别为1.00、0.96、0.92,在T-18 h时,uNGAL的ROC的AUC为0.95。 结论脓毒症AKI患者pNGAL、uNGAL、尿KIM-1、尿TIMP-2表达水平明显早于血肌酐升高,早于AKI临床诊断标准,有望用于脓毒症AKI的早期诊断。     

Clinical risk conditions for acute lung injury in the intensive care unit and hospital ward: a prospective observational study

Background  

Little is known about the development of acute lung injury outside the intensive care unit. We set out to document the following: the association between predefined clinical conditions and the development of acute lung injury by using the American–European consensus definition; the frequency of lung injury development outside the intensive care unit; and the temporal relationship between antecedent clinical risk conditions, intensive care admission, and diagnosis of lung injury.     

Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

Introduction

Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis.

Methods

We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis.

Results

Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI.

Conclusions

The findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis.     

The safety of targeted antibiotic therapy for ventilator-associated pneumonia: a multicenter observational study

PURPOSE: The aim of this study was to determine the safety of targeted antibiotic therapy (TT) in ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: This was a secondary analysis from a multicenter trial of 740 patients with suspected VAP randomized to bronchoscopy or endotracheal aspirate cultures; all received empirical broad-spectrum antibiotics. Patients were grouped by whether they received TT, defined as tailoring or discontinuing antibiotics in response to enrolment culture results. RESULTS: For patients with a positive culture (n = 412), baseline demographics, clinical progression of infection and multiple organ dysfunction scores (MODS), and mortality were similar for those on TT (n = 320) or those who did not receive TT (NoTT) (n = 92). The TT group had more days alive and off broad-spectrum antibiotics (14.5 vs 13.2, P = .04). In patients with a negative culture (n = 327), those on TT (n = 230) had similar baseline demographics, less frequent final adjudicated diagnosis of VAP (63.0% vs 76.3%, P = .02), and less severe clinical progression of infection and MODS compared with NoTT (n = 97). The TT group had more days alive and off broad-spectrum antibiotics (15.9 vs 13.1, P < .001), lower delta MODS (2.0 vs 3.0, P = .01), fewer mechanical ventilation days (9.8 vs 14.7, P = .03), and similar mortality compared to NoTT. CONCLUSIONS: Targeted therapy is associated with less antibiotic use and no evidence of harm in the management of patients with VAP.     

Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study

Introduction

The role of systemic hemodynamics in the pathogenesis of septic acute kidney injury (AKI) has received little attention. The purpose of this study was to investigate the association between systemic hemodynamics and new or persistent of AKI in severe sepsis.

Methods

A retrospective study between 2006 and 2010 was performed in a surgical ICU in a teaching hospital. AKI was defined as development (new AKI) or persistent AKI during the five days following admission based on the Acute Kidney Injury Network (AKIN) criteria. We studied the association between the following hemodynamic targets within 24 hours of admission and AKI: central venous pressure (CVP), cardiac output (CO), mean arterial pressure (MAP), diastolic arterial pressure (DAP), central venous oxygen saturation (ScvO₂) or mixed venous oxygen saturation (SvO₂).

Results

This study included 137 ICU septic patients. Of these, 69 had new or persistent AKI. AKI patients had a higher Simplified Acute Physiology Score (SAPS II) (57 (46 to 67) vs. 45 (33 to 52), P < 0.001) and higher mortality (38% vs. 15%, P = 0.003) than those with no AKI or improving AKI. MAP, ScvO₂ and CO were not significantly different between groups. Patients with AKI had lower DAP and higher CVP (P = 0.0003). The CVP value was associated with the risk of developing new or persistent AKI even after adjustment for fluid balance and positive end-expiratory pressure (PEEP) level (OR = 1.22 (1.08 to 1.39), P = 0.002). A linear relationship between CVP and the risk of new or persistent AKI was observed.

Conclusions

We observed no association between most systemic hemodynamic parameters and AKI in septic patients. Association between elevated CVP and AKI suggests a role of venous congestion in the development of AKI. The paradigm that targeting high CVP may reduce occurrence of AKI should probably be revised. Furthermore, DAP should be considered as a potential important hemodynamic target for the kidney.