Dataset Information

Genetic variants in SERPINA4 and SERPINA5, but not BCL2 and SIK3 are associated with acute kidney injury in critically ill patients with septic shock.

ABSTRACT: Acute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited. Recently the first hypothesis-free genetic association studies have been published to explore individual susceptibility to AKI. We aimed to replicate the previously identified associations between five candidate single nucleotide polymorphisms (SNP) in apoptosis-related genes BCL2, SERPINA4, SERPINA5, and SIK3 and the development of AKI, using a prospective cohort of critically ill patients with sepsis/septic shock, in Finland.This is a prospective, observational multicenter study. Of 2567 patients without chronic kidney disease and with genetic samples included in the Finnish Acute Kidney Injury (FINNAKI) study, 837 patients had sepsis and 627 patients had septic shock. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, considering stages 2 and 3 affected (severe AKI), stage 0 unaffected, and stage 1 indecisive. Genotyping was done using iPLEXTM Assay (Agena Bioscience). The genotyped SNPs were rs8094315 and rs12457893 in the intron of the BCL2 gene, rs2093266 in the SERPINA4 gene, rs1955656 in the SERPINA5 gene and rs625145 in the SIK3 gene. Association analyses were performed using logistic regression with PLINK software.We found no significant associations between the SNPs and severe AKI in patients with sepsis/septic shock, even after adjustment for confounders. Among patients with septic shock (252 with severe AKI and 226 without AKI (149 with KDIGO stage 1 excluded)), the SNPs rs2093266 and rs1955656 were significantly (odds ratio 0.63, p?=?0.04276) associated with stage 2-3 AKI after adjusting for clinical and demographic variables.The SNPs rs2093266 in the SERPINA4 and rs1955656 in the SERPINA5 were associated with the development of severe AKI (KDIGO stage 2-3) in critically ill patients with septic shock. For the other SNPs, we did not confirm the previously reported associations.

SUBMITTER: Vilander LM

PROVIDER: S-EPMC5341446 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Genetic variants in SERPINA4 and SERPINA5, but not BCL2 and SIK3 are associated with acute kidney injury in critically ill patients with septic shock.

Vilander Laura M LM Kaunisto Mari A MA Vaara Suvi T ST Pettilä Ville V

Critical care (London, England) 20170308 1

<h4>Background</h4>Acute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited. Recently the first hypothesis-free genetic association studies have been published to explore individual susceptibility to AKI. We aimed to replicate the previously identified associations between five candidate single nucleotide polymorphisms (SNP) in apoptosis-related genes BCL2, SERPINA4, SERPINA5, and SIK3 and the development of AKI, u ...[more]

PMID: 28270177

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Project description:Sepsis is commonly associated with acute kidney injury (AKI), particularly in those requiring dialysis (AKI-D). To date, Sepsis-3 criteria have not been applied to AKI-D patients. We investigated sepsis prevalence defined by Sepsis-3 criteria and evaluated the outcomes of septic-associated AKI-D among critically ill patients. Using the data collected from a prospective multi-center observational study, we applied the Sepsis-3 criteria to critically ill AKI-D patients treated in intensive care units (ICUs) in 30 hospitals between September 2014 and December 2015. We described the prevalence, outcomes, and characteristics of sepsis as defined by the screening Sepsis-3 criteria among AKI-D patients, and compared the outcomes of AKI-D patients with or without sepsis using the Sepsis-3 criteria. A total of 1078 patients (median 70 years; 673 (62.4%) men) with AKI-D were analyzed. The main etiology of AKI was sepsis (71.43%) and the most frequent indication for acute dialysis was oliguria (64.4%). A total of 577 (53.3% of 1078 patients) met the Sepsis-3 criteria, and 206 among the 577 patients (19.1%) had septic shock. Having sepsis and septic shock were independently associated with 90-day mortality among these ICU AKI-D patients (hazard ratio (HR) 1.23 (p = 0.027) and 1.39 (p = 0.004), respectively). Taking mortality as a competing risk factor, AKI-D patients with septic shock had a significantly reduced chance of weaning from dialysis at 90 days than those without sepsis (HR 0.65, p = 0.026). The combination of the Sepsis-3 criteria with the AKI risk score led to better performance in forecasting 90-day mortality. Sepsis affects more than 50% of ICU AKI patients requiring dialysis, and one-fifth of these patients had septic shock. In AKI-D patients, coexistent with or induced by sepsis (as screened by the Sepsis-3 criteria), there is a significantly higher mortality and reduced chance of recovering sufficient renal function, when compared to those without sepsis.

Project description:BackgroundHaemoadsorption has been described as an effective way to control increased pro- and anti-inflammatory mediators ("cytokine storm") in septic shock patients. No prospective or randomised clinical study has yet confirmed these results. However, no study has yet prospectively specifically investigated patients in severe septic shock with sepsis-associated acute kidney injury (SA-AKI). Therefore, we aimed to examine whether haemoadsorption could influence intensive care unit (ICU) and hospital mortality in these patients. Furthermore, we examined the influence of haemoadsorption on length of stay in the ICU and therapeutic support.MethodsRetrospective control group and prospective intervention group design in a tertiary hospital in central Europe (Germany). Intervention was the implementation of haemoadsorption for patients in septic shock with SA-AKI. 76 patients were included in this analysis.ResultsSeverity of illness as depicted by APACHE II was higher in patients treated with haemoadsorption. Risk-adjusted ICU mortality rates (O/E ratios) did not differ significantly between the groups (0.80 vs. 0.83). We observed in patients treated with haemoadsorption a shorter LOS and shorter therapeutic support such as catecholamine dependency and duration of RRT. However, in multivariate analysis (logistic regression for mortality, competing risk for LOS), we found no significant differences between the two groups.ConclusionsThe implementation of haemoadsorption for patients in septic shock with acute renal failure did not lead to a reduction in ICU or hospital mortality rates. Despite univariate analysis delivering some evidence for a shorter duration of ICU-related treatments in the haemoadsorption group, these results did not remain significant in multivariate analysis. Trial registration CytoSorb® registry https://clinicaltrials.gov/ct2/show/NCT02312024 . December 9, 2014.Databasehttps://www.cytosorb-registry.org/ (registration for content acquisition is necessary).

Project description:BackgroundAssessment of acute kidney injury (AKI) in septic patients remains imprecise. In adults, the classification of septic patients by clinical AKI phenotypes (severity and timing) demonstrates unique associations with patient outcome vs. broadly defined AKI.MethodsIn a multinational prospective observational study, AKI diagnosis in critically ill septic children was stratified by duration (transient vs. persistent) and severity (mild vs. severe by creatinine change and urine output). The outcomes of interest were mortality and intensive care unit resource complexity at 28 days.ResultsSeven hundred and fifty-seven septic children were studied (male 52.7%, age 4.6 years (1.5-11.9)). Mortality (overall 12.1%) was different between severe AKI and mild AKI (18.3 vs. 4.4%, p < 0.001) as well as intensive care unit (ICU) complexity (overall 34.5%, 45 vs. 21.7%, p < 0.001). Patients with Persistent AKI had fewer ICU-free days (17 (7, 21) vs. 24 (17, 26), p < 0.001) and higher ICU complexity (52.8 vs. 22.9%, p = 0.002) than transient AKI, even after exclusion of patients with early mortality. AKI phenotypes incorporating temporal and severity data correlate with unique survival (range 4.4-21.6%) and ICU-free days (range of 15-25 days) CONCLUSIONS: The outcome of septic children with AKI changes by clinical phenotype. Our findings underscore the importance of prognostic enrichment in sepsis and AKI for the purpose of trial design and patient management.ImpactAlthough AKI occurs commonly in patients with sepsis (S-AKI), outcomes for children with S-AKI varies based on the severity and timing of the AKI. Existing S-AKI pediatric data utilize a broad singular definition of kidney injury. Increasing the precision of AKI classification results in a new understanding of how S-AKI associates with patient outcome. A refined classification of S-AKI identifies subgroups of children, making possible a targeted and a personalized medicine approach to S-AKI study and management.

Dataset Information

Genetic variants in SERPINA4 and SERPINA5, but not BCL2 and SIK3 are associated with acute kidney injury in critically ill patients with septic shock.

Publications

Genetic variants in SERPINA4 and SERPINA5, but not BCL2 and SIK3 are associated with acute kidney injury in critically ill patients with septic shock.

Similar Datasets

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