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Plasma proteomic characterization of the development of acute kidney injury in early sepsis patients.

ABSTRACT: Acute kidney injury (AKI) develops frequently in the course of patients with sepsis and strongly associates with in-hospital mortality. However, diagnosing AKI involves a considerable lag-time because it depends on assessing an increase in serum creatinine, and offers no insight in the underlying pathophysiology. Consequently, identifying a set of proteins reflecting the development of AKI may improve earlier recognition of AKI and the understanding of its pathophysiology. A targeted plasma proteomic approach was performed in early sepsis patients with and without subsequent AKI development in a matched pair design (n = 19 each). Principal component analysis identified 53 proteins associated with development of AKI, which were further analysed using Enrichr gene ontology and pathway analysis. Nine differentially expressed proteins from the targeted proteomics were increased among patients who subsequently developed AKI and correlated with principal components, namely CALCA, CALR, CA12, CLEC1A, PTK7, KIM-1, NPPC, NUCB2 and PGF. We demonstrated the biological insight in the development of AKI in early sepsis compared to non-AKI sepsis.

SUBMITTER: Star BS

PROVIDER: S-EPMC9668831 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Plasma proteomic characterization of the development of acute kidney injury in early sepsis patients.

Star B S BS Boahen C K CK van der Slikke E C EC Quinten V M VM Ter Maaten J C JC Henning R H RH Kumar V V Bouma H R HR

Scientific reports 20221116 1

Acute kidney injury (AKI) develops frequently in the course of patients with sepsis and strongly associates with in-hospital mortality. However, diagnosing AKI involves a considerable lag-time because it depends on assessing an increase in serum creatinine, and offers no insight in the underlying pathophysiology. Consequently, identifying a set of proteins reflecting the development of AKI may improve earlier recognition of AKI and the understanding of its pathophysiology. A targeted plasma prot ...[more]

PMID: 36385130

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Project description:ImportanceThe prevalence of obesity is increasing in the intensive care unit (ICU). Although obesity is a known risk factor for chronic kidney disease, its association with early sepsis-associated acute kidney injury (SA-AKI) and their combined association with patient outcomes warrant further investigation.ObjectiveTo explore the association between obesity, early SA-AKI incidence, and clinical outcomes in patients with sepsis.Design, setting, and participantsThis nationwide, prospective cohort study analyzed patients aged 19 years or older who had sepsis and were admitted to 20 tertiary hospital ICUs in Korea between September 1, 2019, and December 31, 2021. Patients with preexisting stage 3A to 5 chronic kidney disease and those with missing body mass index (BMI) values were excluded.ExposuresSepsis and hospitalization in the ICU.Main outcomes and measuresThe primary outcome was SA-AKI incidence within 48 hours of ICU admission, and secondary outcomes were mortality and clinical recovery (survival to discharge within 30 days). Patients were categorized by BMI (calculated as weight in kilograms divided by height in meters squared), and data were analyzed by logistic regression adjusted for key characteristics and clinical factors. Multivariable fractional polynomial regression models and restricted cubic spline models were used to analyze the clinical outcomes with BMI as a continuous variable.ResultsOf the 4041 patients (median age, 73 years [IQR, 63-81 years]; 2349 [58.1%] male) included in the study, 1367 (33.8%) developed early SA-AKI. Obesity was associated with a higher incidence of SA-AKI compared with normal weight (adjusted odds ratio [AOR], 1.40; 95% CI, 1.15-1.70), as was every increase in BMI of 10 (OR, 1.75; 95% CI, 1.47-2.08). While obesity was associated with lower in-hospital mortality in patients without SA-AKI compared with their counterparts without obesity (ie, underweight, normal weight, overweight) (AOR, 0.72; 95% CI, 0.54-0.94), no difference in mortality was observed in those with SA-AKI (AOR, 0.85; 95% CI, 0.65-1.12). Although patients with obesity without SA-AKI had a greater likelihood of clinical recovery than their counterparts without obesity, clinical recovery was less likely among those with both obesity and SA-AKI.Conclusions and relevanceIn this cohort study of patients with sepsis, obesity was associated with a higher risk of early SA-AKI and the presence of SA-AKI modified the association of obesity with clinical outcomes.

Project description:BackgroundIn the context of sepsis patients, hypertension has a significant impact on the likelihood of developing sepsis-associated acute kidney injury (S-AKI), leading to a considerable burden. Moreover, sepsis is responsible for over 50 % of cases of acute kidney injuries (AKI) and is linked to an increased likelihood of death during hospitalization. The objective of this research is to develop a dependable and strong nomogram framework, utilizing the variables accessible within the first 24 h of admission, for the anticipation of S-AKI in sepsis patients who have hypertension.MethodsIn this study that looked back, a total of 462 patients with sepsis and high blood pressure were identified from Nanfang Hospital. These patients were then split into a training set (consisting of 347 patients) and a validation set (consisting of 115 patients). A multivariate logistic regression analysis and a univariate logistic regression analysis were performed to identify the factors that independently predict S-AKI. Based on these independent predictors, the model was constructed. To evaluate the efficacy of the designed nomogram, several analyses were conducted, including calibration curves, receiver operating characteristics curves, and decision curve analysis.ResultsThe findings of this research indicated that diabetes, prothrombin time activity (PTA), thrombin time (TT), cystatin C, creatinine (Cr), and procalcitonin (PCT) were autonomous prognosticators for S-AKI in sepsis individuals with hypertension. The nomogram model, built using these predictors, demonstrated satisfactory discrimination in both the training (AUC = 0.823) and validation (AUC = 0.929) groups. The S-AKI nomogram demonstrated superior predictive ability in assessing S-AKI within the hypertension grade I (AUC = 0.901) set, surpassing the hypertension grade II (AUC = 0.816) and III (AUC = 0.810) sets. The nomogram exhibited satisfactory calibration and clinical utility based on the calibration curve and decision curve analysis.ConclusionIn patients with sepsis and high blood pressure, the nomogram that was created offers a dependable and strong evaluation for predicting S-AKI. This evaluation provides valuable insights to enhance individualized treatment, ultimately resulting in improved clinical outcomes.

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Plasma proteomic characterization of the development of acute kidney injury in early sepsis patients.

Publications

Plasma proteomic characterization of the development of acute kidney injury in early sepsis patients.

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