Use of Biomarkers to Identify Acute Kidney Injury to Help Detect Sepsis in Patients With Infection

Kellum, John A.; Artigas, Antonio; Gunnerson, Kyle J.; Honoré, Patrick M.; Kampf, J. Patrick; Kwan, Thomas; McPherson, Paul; Nguyen, H. Bryant; Rimmelé, Thomas; Shapiro, Nathan I.; Shi, Jing; Vincent, Jean‐Louis; Chawla, Lakhmir S.; Investigators, Sapphire

doi:10.1097/ccm.0000000000004845

Cited by 16 publications

(10 citation statements)

References 22 publications

(14 reference statements)

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“…[14][15][16][17] Given the impact sepsis-associated AKI has on morbidity and mortality, 3 prevention is imperative. The first step to successfully prevent AKI is an 19,20 Building on this, the implementation of protective measures may provide a way to improve outcomes, even if previous research has indicated that the pathophysiology of septic AKI may differ in parts from AKI induced by other causes. 21 The assumption that standard AKI prevention measures, like hemodynamic optimization and goaldirected therapy approaches to fluid resuscitation, may be insufficient in preventing sepsis-associated AKI has been fueled by null results regarding AKI incidence in major trials of early goal-directed therapy.…”

Section: Discussionmentioning

confidence: 99%

Implementation of Nephroprotective Measures to Prevent Acute Kidney Injury in Septic Patients: A Retrospective Cohort Study

Sadjadi

Porschen

Groote

et al. 2023

Anesthesia &Amp; Analgesia

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BACKGROUND: Sepsis remains the leading cause of mortality in critically ill patients, and mortality is increased when acute kidney injury (AKI) occurs. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends the implementation of supportive measures in patients at high risk for AKI. However, it remains unclear to what extent these nephroprotective measures are implemented in daily clinical practice in critically ill patients, especially those with high-risk exposures such as sepsis. METHODS: We analyzed the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to identify septic patients with and without AKI. The primary outcome of interest was the adherence to the KDIGO bundle consisting of avoidance of nephrotoxic agents, implementation of a functional hemodynamic monitoring, optimization of perfusion pressure and volume status, close monitoring of renal function, avoidance of hyperglycemia, and avoidance of radiocontrast agents. Secondary outcomes included the development of AKI, progression of AKI, the use of renal replacement therapy (RRT), mortality, and a composite end point consisting of progression of AKI and mortality within 7 days. RESULTS: Our analysis included 34,679 patients with sepsis with 1.6% receiving the complete bundle (10% received 5, 42.3% 4, 35.4% 3, and 9.8% 2 bundle components). In 56.4%, nephrotoxic agents were avoided, and hemodynamic optimization was reached in 86.5%. Secondary end points were improved in patients with bundle adherence. Avoidance of nephrotoxic drugs and optimization of hemodynamics were significantly associated with lower rates of AKI and improved patient outcomes, including 30-day mortality. CONCLUSIONS: Implementation of the KDIGO bundle is poor in patients with sepsis but may be associated with improved outcomes.

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Section: Discussionmentioning

confidence: 99%

Implementation of Nephroprotective Measures to Prevent Acute Kidney Injury in Septic Patients: A Retrospective Cohort Study

Sadjadi

Porschen

Groote

et al. 2023

Anesthesia &Amp; Analgesia

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“…The pathophysiology of sepsis-related organ dysfunction is characterized by dysregulated host responses, including inflammation and immunosuppression (2). The kidney is one of the most vulnerable organs in sepsis, with acute kidney injury (AKI) occurring in more than 50% of patients (3). Early identification is key to providing supportive care and limiting further insult (4).…”

Section: Introductionmentioning

confidence: 99%

Circ_0001818 targets miR-136-5p to increase lipopolysaccharide-induced HK2 cell injuries by activating TXNIP/NLRP3 inflammasome pathway

Feng

Wang

You

et al. 2023

Shock

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Background: The implication of circular RNAs (circRNAs) in sepsis-related complications arouses much attention, which provides additional treatment options for sepsis-related complications. The purpose of this study is to unveil the function and functional mechanism of circ_0001818 in cell models of septic acute kidney injury (AKI). Methods: Septic AKI cell models were constructed using HK2 cells treated with lipopolysaccharide (LPS). The expression levels of circ_0001818, miR-136-5p, and thioredoxin interacting protein (TXNIP) mRNA were examined by quantitative real-time polymerase chain reaction. Cell viability and death were explored by CCK-8 and flow cytometry assays. The activity of oxidative stress-related markers was examined using commercial kits. The secretion of inflammatory factors was examined using ELISA kits. The binding between miR-136-5p and circ_0001818 or TXNIP was validated by dual-luciferase reporter test and pull-down assay. The receiver operating characteristic curve was depicted to assess the diagnostic value of circ_0001818, miR-136-5p, and TXNIP in serumal exosomes from patients with septic AKI. Results: Circ_0001818 expression was elevated in LPS-treated HK2 cells. Loss-offunction assays displayed that circ_0001818 downregulation alleviated LPS-induced HK2 cell death, oxidative stress, inflammatory release, and inflammasome activation. MiR-136-5p was targeted by circ_0001818, and inhibition of miR-136-5p attenuated the effects of circ_0001818 downregulation, thus recovering LPS-induced HK2 cell injuries. MiR-136-5p targeted the downstream TXNIP, and circ_0001818 dysregulation could affect TXNIP expression via targeting miR-136-5p. Overexpression of TXNIP overturned the effects of circ_0001818 downregulation. Moreover, circ_0001818, miR-136-5p, and TXNIP in serumal exosomes had diagnostic values. Conclusions: Circ_0001818 targets miR-136-5p to activate TXNIP expression, leading to the contribution of LPS-induced HK2 cell injury.

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“…Point-of-care C-reactive protein, procalcitonin, or lactate levels have also been proposed to help potentially identify those patients with infection at risk of progressing to sepsis in the community setting, although the benefit of such testing in nonhospitalized patients warrants further study (17,(22)(23)(24). Urinary biomarkers may hold promise in detecting organ injury from sepsis, as the urinary product of tissue inhibitor of metalloproteinase-2 × insulin-like growth factor binding protein 7 (NephroCheck Astute Medical, Inc., San Diego, CA) may help detect sepsis-related kidney injury in patients with infection (but not meeting sepsis criteria) nearly 1 day prior to traditional criteria of serum creatinine and urine output being met (25). Additional point-of-care technologies are also in development for molecular and immune-based diagnostics (26).…”

Section: Discussionmentioning

confidence: 99%

Frequency and Types of Healthcare Encounters in the Week Preceding a Sepsis Hospitalization: A Systematic Review

Flannery¹,

Venn²,

Gusovsky³

et al. 2022

Critical Care Explorations

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OBJECTIVES: Early recognition and treatment are critical to improving sepsis outcomes. We sought to identify the frequency and types of encounters that patients have with the healthcare system in the week prior to a sepsis hospitalization. DATA SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and the Cochrane Library. STUDY SELECTION: Observational cohort studies of patients hospitalized with sepsis or septic shock that were assessed for an outpatient or emergency department encounter with the healthcare system in the week prior to hospital admission. DATA EXTRACTION: The primary outcome was the proportion of patients with a healthcare encounter in the time period assessed (up to 1 week) prior to a hospitalization with sepsis. DATA SYNTHESIS: Six retrospective observational studies encompassing 6,785,728 sepsis admissions were included for evaluation, ranging from a 263-patient single-center cohort to a large database evaluating 6,731,827 sepsis admissions. The average (unweighted) proportion of patients having an encounter with the healthcare system in the week prior to a sepsis hospitalization was 32.7% and ranged from 10.3% to 52.9%. These encounters commonly involved presentation or potential symptoms of infectious diseases, antibiotic prescriptions, and appeared to increase in frequency closer to a sepsis hospitalization admission. No consistent factors were identified that distinguished a healthcare encounter as more or less likely to precede a sepsis hospitalization in the subsequent week. CONCLUSIONS: Patients that present to the hospital with sepsis are frequently evaluated in the healthcare system in the week prior to admission. Further research is necessary to understand if these encounters offer earlier opportunities for intervention to prevent the transition from infection to sepsis, whether they merely reflect the comorbidities of sepsis patients with a high baseline rate of healthcare encounters, or the declining trajectory of a patient’s overall health in response to infection.

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Use of Biomarkers to Identify Acute Kidney Injury to Help Detect Sepsis in Patients With Infection

Abstract: Supplemental Digital Content is available in the text.

Cited by 16 publications

References 22 publications

Implementation of Nephroprotective Measures to Prevent Acute Kidney Injury in Septic Patients: A Retrospective Cohort Study

Implementation of Nephroprotective Measures to Prevent Acute Kidney Injury in Septic Patients: A Retrospective Cohort Study

Circ_0001818 targets miR-136-5p to increase lipopolysaccharide-induced HK2 cell injuries by activating TXNIP/NLRP3 inflammasome pathway

Frequency and Types of Healthcare Encounters in the Week Preceding a Sepsis Hospitalization: A Systematic Review

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