Fluid management in patients with acute kidney injury-A post-hoc analysis of the FINNAKI study

Purpose: Whether positive fluid balance among patients with acute kidney injury (AKI) stems from decreased urine output, overzealous fluid administration, or both is poorly characterized. Materials and methods: This was a post hoc analysis of the prospective multicenter observational Finnish Acute Kidney Injury study including 824 AKI and 1162 non-AKI critically ill patients. Results: We matched 616 AKI (diagnosed during the three first intensive care unit (ICU) days) and non-AKI patients using propensity score. During the three first ICU days, AKI patients received median [IQR] of 11.4 L [8.0-15.2]L fluids and non-AKI patients 10.2 L [7.5-13.7]L, p < 0.001 while the fluid output among AKI patients was 4.7 L [3.0-7.2]L and among non-AKI patients 5.8 L [4.1-8.0]L, p < 0.001. In AKI patients, the median [IQR] cumulative fluid balance was 2.5 L [-0.2-6.0]L compared to 0.9 L [-1.4-3.6]L among non-AKI patients, p < 0.001. Among the 824 AKI patients, smaller volumes of fluid input with a multivariable OR of 0.90 (0.88-0.93) and better fluid output (multivariable OR 1.12 (1.07-1.18)) associated with enhanced change of resolution of AKI. Conclusions: AKI patients received more fluids albeit having lower fluid output compared to matched critically ill non-AKI patients. Smaller volumes of fluid input and higher fluid output were associated with better AKI recovery. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Identifying Cultural and Cognitive Proximity between Managers and Customers in Tornio and Haparanda Cross Border Region

Daily intercultural interactions in cross-border regions such as those between customers and managers can be a source of knowledge and ideas. However, such interactions can pose distinctive constraints and opportunities for learning and exchange of ideas. This study adopts a relatively fine–grained quantitative approach to study elements of cognitive and cultural proximity which have a major impact on these interactions. It is based on a survey of 91 managers of small service firms and 312 customers in the twin city of Tornio and Haparanda on the border between Finland and Sweden. Seven elements of proximity were identified and measured. Six elements of perceived cognitive and cultural proximity including values, conservative values towards new ideas, knowledge and use of technology, use of a foreign language, sufficiently focusing or providing specific details and ways of solving problems were found significant in terms of shaping perceptions of Swedish and Finnish managers and customers, which shape these interactions. The results enhance our understanding of how daily cross-border intercultural can be examined in the context of cross-border regional knowledge transfer

Association of endothelial and glycocalyx injury biomarkers with fluid administration, development of acute kidney injury, and 90-day mortality : data from the FINNAKI observational study

Abstract Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p  12 h from ICU admission (AKI>12 h). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI>12 h with OR (95% CI) of 12.71 (2.96–54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31–3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29–23.57], p < 0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44–4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67–11.79; p < 0.001) for 90-day mortality. Conclusions VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality

Two subphenotypes of septic acute kidney injury are associated with different 90-day mortality and renal recovery

Background The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcomes. Methods We performed a post hoc analysis of the prospective Finnish Acute Kidney Injury (FINNAKI) study cohort. We included patients admitted with sepsis and acute kidney injury during the first 48 h from admission to intensive care (according to Kidney Disease Improving Global Outcome criteria). Primary outcomes were 90-day mortality and renal recovery on day 5. We performed latent class analysis using 30 variables obtained on admission to classify subphenotypes. Second, we used logistic regression to assess the association of derived subphenotypes with 90-day mortality and renal recovery on day 5. Results In total, 301 patients with septic acute kidney injury were included. Based on the latent class analysis, a two-class model was chosen. Subphenotype 1 was assigned to 133 patients (44%) and subphenotype 2 to 168 patients (56%). Increased levels of inflammatory and endothelial injury markers characterized subphenotype 2. At 90 days, 29% of patients in subphenotype 1 and 41% of patients in subphenotype 2 had died. Subphenotype 2 was associated with a lower probability of short-term renal recovery and increased 90-day mortality. Conclusions In this post hoc analysis, we identified two subphenotypes of septic acute kidney injury with different clinical outcomes. Future studies are warranted to validate the suggested subphenotypes of septic acute kidney injury.Peer reviewe

Genetic risk factors have a substantial impact on healthy life years

The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; 'lost healthy life years'). We use genetic information from 735,748 individuals and consider 80 diseases. Rare variants had the highest effect on DALYs at the individual level. Among common variants, rs3798220 (LPA) had the strongest individual-level effect, with 1.18 DALYs from carrying 1 versus 0 copies. Being in the top 10% versus the bottom 90% of a polygenic score for multisite chronic pain had an effect of 3.63 DALYs. Some common variants had a population-level effect comparable to modifiable risk factors such as high sodium intake and low physical activity. Attributable DALYs vary between males and females for some genetic exposures. Genetic risk factors can explain a sizable number of healthy life years lost both at the individual and population level.Peer reviewe

Association of endothelial and glycocalyx injury biomarkers with fluid administration, development of acute kidney injury, and 90-day mortality: data from the FINNAKI observational study

Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality. Results SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p 12 h from ICU admission (AKI(>12 h)). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI(>12 h) with OR (95% CI) of 12.71 (2.96-54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31-3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29-23.57], p < 0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44-4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67-11.79; p < 0.001) for 90-day mortality. Conclusions VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality

Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases

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Overlap of genetic loci for central serous chorioretinopathy with age-related macular degeneration

IMPORTANCE Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases.OBJECTIVE To identify novel genetic risk factors for CSC and compare genetic risk factors for CSC and AMD.DESIGN, SETTING, AND PARTICIPANTS Using International Classification of Diseases, Ninth (ICD-9) and Tenth (ICD-10) Revision code-based inclusion and exclusion criteria, patients with CSC and controls were identified in both the FinnGen study and the Estonian Biobank (EstBB). Also included in ameta-analysis were previously reported patients with chronic CSC and controls. Data were analyzed from March 1 to September 31, 2022.MAIN OUTCOMES AND MEASURES Genome-wide association studies (GWASs) were performed in the biobank-based cohorts followed by ameta-analysis of all cohorts. The expression of genes prioritized by the polygenic priority score and nearest-gene methods were assessed in cultured choroidal endothelial cells and public ocular single-cell RNA sequencing data sets. The predictive utility of polygenic scores (PGSs) for CSC and AMD were evaluated in the FinnGen study.RESULTS A total of 1176 patients with CSC and 526 787 controls (312 162 female [59.3%]) were included in this analysis: 552 patients with CSC and 343 461 controls were identified in the FinnGen study, 103 patients with CSC and 178 573 controls were identified in the EstBB, and 521 patients with chronic CSC and 3577 controls were included in ameta-analysis. Two previously reported CSC risk loci were replicated (near CFH and GATA5) and 3 novel loci were identified (near CD34/46, NOTCH4, and PREX1). The CFH and NOTCH4 loci were associated with AMD but in the opposite direction. Prioritized genes showed increased expression in cultured choroidal endothelial cells compared with other genes in the loci (median [IQR] of log 2 [counts per million], 7.3 [0.6] vs 4.7 [3.7]; P =.004) and were differentially expressed in choroidal vascular endothelial cells in single-cell RNA sequencing data (mean [SD] fold change, 2.05 [0.38] compared with other cell types; P < 7.1 x 10(-20)). A PGS for AMD was predictive of reduced CSC risk (odds ratio, 0.76; 95% CI, 0.70-0.83 per +1 SD in AMD-PGS; P = 7.4 x 10(-10)). This association may have been mediated by loci containing complement genes.CONCLUSIONS AND RELEVANCE In this 3-cohort genetic association study, 5 genetic risk loci for CSC were identified, highlighting a likely role for genes involved in choroidal vascular function and complement regulation. Results suggest that polygenic AMD risk was associated with reduced risk of CSC and that this genetic overlap was largely due to loci containing complement genes.Ophthalmic researc

Different applications of the KDIGO criteria for AKI lead to different incidences in critically ill patients : a post hoc analysis from the prospective observational SICS-II study

Background Acute kidney injury (AKI) is a frequent and clinically relevant problem in critically ill patients. Various randomized controlled trials (RCT) have attempted to assess potentially beneficial treatments for AKI. Different approaches to applying the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI make a comparison of studies difficult. The objective of this study was to assess how different approaches may impact estimates of AKI incidence and whether the association between AKI and 90-day mortality varied by the approach used. Methods Consecutive acutely admitted adult intensive care patients were included in a prospective observational study. AKI was determined following the KDIGO criteria during the first 7 days of ICU admission. In this post hoc analysis, we assessed whether AKI incidence differed when applying the KDIGO criteria in 30 different possible methods, varying in (A) serum creatinine (sCr), (B) urine output (UO), and (C) the method of combining these two into an outcome, e.g., severe AKI. We assessed point estimates and 95% confidence intervals for each incidence. Univariable regression was used to assess the associations between AKI and 90-day mortality. Results A total of 1010 patients were included. Baseline creatinine was available in 449 (44%) patients. The incidence of any AKI ranged from 28% (95%CI 25-31%) to 75% (95%CI 72-77%) depending on the approach used. Methods to estimate missing baseline sCr caused a variation in AKI incidence up to 15%. Different methods of handling UO caused a variation of up to 35%. At 90 days, 263 patients (26%) had died, and all 30 variations were associated with 90-day mortality. Conclusions In this cohort of critically ill patients, AKI incidence varied from 28 to 75%, depending on the method used of applying the KDIGO criteria. A tighter adherence to KDIGO definitions is warranted to decrease the heterogeneity of AKI and increase the comparability of future studies.Peer reviewe