Sara Nisula

Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

IntroductionPositive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.MethodsWe conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.ResultsWe included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.ConclusionsPatients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.

Six-month survival and quality of life of intensive care patients with acute kidney injury.

IntroductionAcute kidney injury (AKI) has high incidence among the critically ill and associates with dismal outcome. Not only the long-term survival, but also the quality of life (QOL) of patients with AKI is relevant due to substantial burden of care regarding these patients. We aimed to study the long-term outcome and QOL of patients with AKI treated in intensive care units.MethodsWe conducted a predefined six-month follow-up of adult intensive care unit (ICU) patients from the prospective, observational, multi-centre FINNAKI study. We evaluated the QOL of survivors with the EuroQol (EQ-5D) questionnaire. We included all participating sites with at least 70% rate of QOL measurements in the analysis.ResultsOf the 1,568 study patients, 635 (40.5%, 95% confidence interval (CI) 38.0-43.0%) had AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of the 635 AKI patients, 224 (35.3%), as compared to 154/933 (16.5%) patients without AKI, died within six months. Of the 1,190 survivors, 959 (80.6%) answered the EQ-5D questionnaire at six months. The QOL (median with Interquartile range, IQR) measured with the EQ-5D index and compared to age- and sex-matched general population was: 0.676 (0.520-1.00) versus 0.826 (0.812-0.859) for AKI patients, and 0.690 (0.533-1.00) versus 0.845 (0.812-0.882) for patients without AKI (P <0.001 in both). The EQ-5D at the time of ICU admission was available for 774 (80.7%) of the six-month respondents. We detected a mean increase of 0.017 for non-AKI and of 0.024 for AKI patients in the EQ-5D index (P = 0.728). The EQ-5D visual analogue scores (median with IQR) of patients with AKI (70 (50–83)) and patients without AKI (75 (60–87)) were not different from the age- and sex-matched general population (69 (68–73) and 70 (68–77)).ConclusionsThe health-related quality of life of patients with and without AKI was already lower on ICU admission than that of the age- and sex-matched general population, and did not change significantly during critical illness. Patients with and without AKI rate their subjective health to be as good as age and sex-matched general population despite statistically significantly lower QOL indexes measured by EQ-5D.

Association of oliguria with the development of acute kidney injury in the critically ill

Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria (<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy (RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%) developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6-12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h. Thus, our findings underlie the importance of hourly UO measurements.Kidney International advance online publication, 9 September 2015; doi:10.1038/ki.2015.269.

Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study

Abstract Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72–1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22–0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury.

The urine protein NGAL predicts renal replacement therapy, but not acute kidney injury or 90-day mortality in critically ill adult patients.

BACKGROUND:Urine neutrophil gelatinase-associated lipocalin (uNGAL) is increasingly used as a biomarker for acute kidney injury (AKI). However, the clinical value of uNGAL with respect to AKI, renal replacement therapy (RRT), or 90-day mortality in critically ill patients is unclear. Accordingly, we tested the hypothesis that uNGAL is a clinically relevant biomarker for these end points in a large, nonselected cohort of critically ill adult patients. METHODS:We prospectively obtained urine samples from 1042 adult patients admitted to 15 Finnish intensive care units. We analyzed 3 samples (on admission, at 12 hours, and at 24 hours) with NGAL ELISA Rapid Kits (BioPorto® Diagnostics, Gentofte, Denmark). We chose the highest uNGAL (uNGAL24) for statistical analyses. We calculated the areas under receiver operating characteristics curves (AUC) with 95% confidence intervals (95% CIs), the best cutoff points with the Youden index, positive likelihood ratios (LR+), continuous net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). We performed sensitivity analyses excluding patients with AKI or RRT on day 1, sepsis, or with missing baseline serum creatinine concentration. RESULTS:In this study population, the AUC of uNGAL24 (95% CI) for development of AKI (defined by the Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was 0.733 (0.701–0.765), and the continuous NRI for AKI was 56.9%. For RRT, the AUC of uNGAL24 (95% CI) was 0.839 (0.797–0.880), and NRI 56.3%. For 90-day mortality, the AUC of uNGAL24 (95% CI) was 0.634 (0.593 to 0.675), and NRI 15.3%. The LR+ (95% CI) for RRT was 3.81 (3.26–4.47). CONCLUSION:In this study, we found that uNGAL associated well with the initiation of RRT but did not provide additional predictive value regarding AKI or 90-day mortality in critically ill patients.

Acute Kidney Injury After Cardiac Surgery by Complete KDIGO Criteria Predicts Increased Mortality.

OBJECTIVES Acute kidney injury (AKI) occurs frequently after cardiac surgery and is associated with increased mortality. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria for diagnosing AKI include creatinine and urine output values. However, the value of the latter is debated. The authors aimed to evaluate the incidence of AKI after cardiac surgery and the independent association of KDIGO criteria, especially the urine output criterion, and 2.5-year mortality. DESIGN Prospective, observational, cohort study. SETTING Single-center study in a university hospital. PARTICIPANTS The study comprised 638 cardiac surgical patients from September 1, 2011, to June 20, 2012. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Hourly urine output, daily plasma creatinine, risk factors for AKI, and variables for EuroSCORE II were recorded. AKI occurred in 183 (28.7%) patients. Patients with AKI diagnosed using only urine output had higher 2.5-year mortality than did patients without AKI (9/53 [17.0%] v 23/455 [5.1%], p = 0.001). AKI was associated with mortality (hazard ratios [95% confidence intervals]: 3.3 [1.8-6.1] for KDIGO 1; 5.8 [2.7-12.1] for KDIGO 2; and 7.9 [3.5-17.6]) for KDIGO 3. KDIGO stages and AKI diagnosed using urine output were associated with mortality even after adjusting for mortality risk assessed using EuroSCORE II and risk factors for AKI. CONCLUSIONS AKI diagnosed using only the urine output criterion without fulfilling the creatinine criterion and all stages of AKI were associated with long-term mortality. Preoperatively assessed mortality risk using EuroSCORE II did not predict this AKI-associated mortality.

Epidemiology of AKI

The reported incidence rates of AKI are strongly influenced both by the definition of AKI used and the studied population (all citizens/all hospitalized patients/all ICU-treated patients/only those with renal replacement therapy). So far only two studies [1, 2] (_ENREF_1both using RIFLE criteria) have used any of the recent definitions (RIFLE, AKIN, KDIGO – See Chap. 1) to evaluate the population-based incidence. The first retrospective study from Scotland representing a population of 523,390 reported the population-based incidence of hospital-treated AKI as 214/100,000/year [1]. Another retrospective study from one USA county area comprising a population of 124,277 reported a population-based incidence of 290/100,000/year for ICU-treated AKI [2]. Previously, the community-based incidence of non-RRT-requiring and RRT-requiring AKI in Northern California was estimated to be 384.1 and 24.4 per 100,000/year, respectively [3]. Most recently, in the FINNAKI study, the population-based incidence of ICU-treated AKI was 74.6/100,000 adults/year using both KDIGO creatinine and urine output criteria [4].