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Background: Sepsis‐associated acute kidney injury (SA‐AKI) is a common complication that can lead to renal failure in patients, significantly affecting the prognosis and survival of patients. Objective: In this study, we aimed to evaluate the predictive value of NOD‐like receptor protein 3 (NLRP3) and interleukin 18 (IL‐18) in peripheral blood mononuclear cells (PBMCs) of SA patients for the occurrence of SA‐AKI. Material and Methods: We screened AKI‐related data sets using the Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs) associated with AKI. KEGG and GO analysis were used to identify enriched molecular functions and pathways. The study included 62 SA patients admitted to the Department of Intensive Care Medicine of our hospital from February 2021 to June 2022, including 34 non‐AKI cases and 28 AKI cases, and 25 healthy volunteers were used as the control group. Real‐time quantitative polymerase chain reaction (RT‐qPCR) was used to detect the levels of NLRP3 and IL‐18 in PBMCs of the subjects. Results: Bioinformatics analysis and experimental validation showed that the expression levels of NLRP3 and IL‐18 were significantly upregulated in SA‐AKI patients. In addition, the expressions of NLRP3 and IL‐18 were positively correlated with APACHE II scores. ROC curve analysis revealed that NLRP3 and IL‐18 have the potential to diagnose SA‐AKI. Conclusion: This study provides preliminary evidence for NLRP3 and IL‐18 as potential diagnostic biomarkers for SA‐AKI. [ABSTRACT FROM AUTHOR]

Summary: Background: Acute kidney injury (AKI), particularly community-acquired AKI (CA-AKI), is a major health concern globally. The International Society of Nephrology's “0 by 25” initiative to reduce preventable deaths from AKI to zero by 2025 is not achievable in low and middle income countries, such as India, possibly due to a lack of data and measures to tackle this urgent public health issue. In India, CA-AKI predisposes younger patients to hospitalization, morbidity, and mortality. This is the first multicenter, prospective, cohort study investigating CA-AKI and its consequences in India. Methods: This study included data from patients with CA-AKI (>12 years of age) housed in the Indian Society of Nephrology-AKI registry, involving 9 participating tertiary care centers in India, for the period between November 2016 and October 2019. The etiological spectrum and renal and patient outcomes of CA-AKI at the index visit and at 1-month and 3-month follow-ups were analyzed. The impact of socioeconomic status (SES) on outcomes was also analyzed. Findings: Data from 3711 patients (mean [±SD] age 44.7 ± 16.5 years; 66.6% male) were analyzed. The most common comorbidities included hypertension (21.1%) and diabetes (19.1%). AKI occurred in medical, surgical, and obstetrical settings in 86.7%, 7.3%, and 6%, respectively. The most common causes of AKI were associated with sepsis (34.7%) and tropical fever (9.8%). Mortality at the index admission was 10.8%. Complete recovery (CR), partial recovery (PR), and dialysis dependency among survivors at the time of discharge were 22.1%, 57.7%, and 9.4%, respectively. Overall, at 3 months of follow-up, mortality rate, CR, PR, and dialysis dependency rates were 11.4%, 72.2%, 7.2%, and 1%, respectively. Multivariate analysis revealed that age >65 years, alcoholism, anuria, hypotension at presentation, thrombocytopenia, vasopressor use, transaminitis, and low SES were associated with mortality at the index admission. Interpretation: Sepsis and tropical fever were the most common causes of CA-AKI. Presentation of CA-AKI to tertiary care units was associated with high mortality, and a significant number of patients progressed to CKD. Individuals with a low SES had increased risk of mortality and require immediate attention and intervention. Funding: This study was funded by the Indian Society of Nephrology.

Curcumin and bone marrow stem cells (BMSCs)-derived exosomes are considered to be useful for the treatment of many human diseases, including sepsis-associated acute kidney injury (SA-AKI). However, the role and underlying molecular mechanism of curcumin-loaded BMSCs-derived exosomes in the progression of SA-AKI remain unclear. Exosomes (BMSCs-EXO Curcumin or BMSCs-EXO Control ) were isolated from curcumin or DMSO-treated BMSCs, and then co-cultured with LPS-induced HK2 cells. Cell proliferation and apoptosis were determined by cell counting kit 8 (CCK8) assay, 5-ethynyl-2-deoxyuridine (EdU) assay, and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used for examining inflammatory factors. The levels of SOD, MDA, and ROS were tested to assess oxidative stress. The levels of fat mass and obesity-associated protein (FTO) and oxidative stress responsive 1 (OXSR1) were detected by quantitative real-time PCR and western blot. Methylated RNA immunoprecipitation (MeRIP) assay and RNA immunoprecipitation (RIP) assay were used for measuring the interaction between FTO and OXSR1. BMSCs-EXO Curcumin treatment could inhibit LPS-induced HK2 cell apoptosis, inflammation, and oxidative stress. FTO was downregulated in SA-AKI patients and LPS-induced HK2 cells, while was upregulated in BMSCs-EXO Curcumin . Exosomal FTO from curcumin-induced BMSCs suppressed apoptosis, inflammation, and oxidative stress in LPS-induced HK2 cells. FTO decreased OXSR1 expression through m6A modification, and the inhibitory effect of FTO on LPS-induced HK2 cell injury could be eliminated by OXSR1 overexpression. In animal experiments, BMSCs-EXO Curcumin alleviated kidney injury in SA-AKI mice models by regulating FTO/OXSR1 axis. In conclusion, exosomal FTO from curcumin-induced BMSCs reduced OXSR1 expression to alleviate LPS-induced HK2 cell injury and improve kidney function in CLP-induced mice models, providing a new target for SA-AKI., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Introduction: Sepsis is defined as life-threatening organ dysfunction in result of the host's dysregulated response to infection and septic shock. Sepsis-associated kidney injury is usually defined as concurrent presence of acute kidney injury (AKI) and sepsis without other significant causative factors. Method: The current retrospective study was conducted to elucidate beneficial and side effects of CytoSorb®. A total of 17 patients were primarily treated with continuous renal replacement therapy in combination with CytoSorb. The demand for norepinephrine, mean arterial pressure, lactate, and procalcitonin (PCT) levels, as well as ICU length of stay, was measured. Result: The blood lactate levels decreased by 32.30% when comparing mean levels before and after treatment. All patients who survived (n = 14) had reduction in vasopressor demand to 68.96% of their initial dose before the start of treatment. Hospital survival was greater in patients who initially had higher vasopressor demand compared to their nonsurviving counterparts, but in whom vasopressor dosages were reduced significantly during their treatments. Mortality as predicted by APACHE II score in the overall patient population was 79.9%, whereas, the observed ICU mortality was 31%. The baseline PCT levels on patients received 1, 2, and 3 CytoSorbs were 27.08 ± 5.81 ng/mL, 13.28 ± 2.62 ng/mL, and 21.03 ± 6.56 ng/mL, respectively. Observed PCT levels at 24 h after the last treatment on patients received 1, 2, and 3 CytoSorb were 31.55 ± 15.70 ng/mL, 5.61 ± 1.77 ng/mL, and 8.11 ± 3.62 ng/mL, respectively. Conclusion: In conclusion, it seems that applying the CytoSorb in combination with CRRT in ICU septic patients with AKI, is related to a significant decrease in mortality, if the integrity and continuity of the treatment be kept, as much as possible. This study presented an effectively positive outcome with cytokine adsorber treatment as an adjuvant along with standard treatment in a high-risk mortality case of septic shock with organ failure. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is one of the most frequent pathophysiologic disorders encountered in hospitalized patients, with sepsis frequently implicated in pathogenesis. Reactive oxygen species (ROS) seem to have a significant contribution to sepsis-induced AKI. Proposed mechanisms include induction of cell membrane lipid peroxidation, protein denaturing, and direct DNA damage, all of which have deleterious effect. These changes constitute oxidative injury to the kidneys. Objective: To evaluate the antioxidant actions of indirect bilirubin and uric acid on outcomes of sepsis-associated AKI. Methods: Ninety-eight patients admitted to the intensive care unit (ICU), at a large tertiary center, with sepsis and AKI were evaluated for serum levels of uric acid, bilirubin (primarily indirect), and procalcitonin. The primary endpoints studied were the need for hemodialysis and death. Results: Thirty-two (33%) patients developed AKI requiring hemodialysis (HD). These patients had higher SOFA scores (p < 0.001) and lower levels of indirect bilirubin (p < 0.001) compared to those not requiring HD. There was no statistically significant difference in serum uric acid levels. Logistic regression analysis identified creatinine level, total and indirect bilirubin levels, and leukocyte count as significant predictors of patient death. Conclusion: Higher leukocyte counts and creatinine levels were independently associated with poor outcomes in ICU patients with sepsis. Additionally, lower indirect bilirubin levels were also noted to be associated with similar outcomes. The latter provides insights into oxidative stress as a major player in the pathogenesis of sepsis-induced AKI, with a potential protective role of indirect bilirubin. [ABSTRACT FROM AUTHOR]

Abstract Background Recent studies have suggested a low potential risk for contrast medium-induced kidney injury in patients with relatively normal renal function. However, whether contrast media cause additional deterioration of renal function in patients with acute kidney injury (AKI), including those with sepsis-associated AKI, remains unclear. This study aimed to evaluate the effect of contrast media on renal function and mortality in patients with sepsis who already had AKI. Methods We performed a propensity score-matched historical cohort study in the medico-surgical intensive care unit of Jichi Medical University Hospital. Adult patients who were diagnosed with sepsis and AKI were enrolled. Records from our sepsis database from 2011 to 2017 were examined. Septic patients with AKI who received contrast media within 24 h of admission (C group) were matched 1:1 with septic patients who did not receive contrast media (NC group). The primary outcome was deterioration of kidney function (DRF), which was defined as an elevation of serum creatinine levels (> 0.3 mg/dL or 1.5-fold from baseline) or induction of renal replacement therapy. Results A total of 339 septic patients with AKI were included. After propensity score adjustment, the DRF rate was similar between the C and NC groups (34.0% versus 35.0%; P = 1.00). The 7-day mortality (3.0% versus 6.0%; P = 0.50), 28-day mortality (9.2% versus 15.0%; P = 0.25), and 90-day mortality (25.8% versus 32.1%; P = 0.45) rates were comparable between the two groups. In propensity-adjusted subsets of a high-risk subset (AKI stages 2 and 3 on admission), the rate of DRF was also similar between the two groups. Conclusions A single administration of contrast media was not associated with exacerbation of AKI or increased short/long-term mortality in patients with sepsis.

It was recently proposed to distinguish early from late sepsis-associated acute kidney injury (SA-AKI). We aimed to determine the relative frequency of these entities in critically ill patients and to describe their characteristics and outcomes. We included in this retrospective cohort study all adult patients admitted for sepsis in a tertiary ICU between 2010 and 2020. We excluded those on chronic dialysis or without consent. We extracted serum creatinine, hourly urinary output, and clinical and socio-demographic data from medical records until day 7 or ICU discharge. AKI presence and characteristics were assessed daily using KDIGO criteria. We compared patients with early (occurring within 2 days of admission) or late (occurring between day 2 and day 7) SA-AKI. We conducted sensitivity analyses using different definitions for early/late SA-AKI. Among 1835 patients, 1660 (90%) fulfilled SA-AKI criteria. Of those, 1610 (97%) had early SA-AKI, and 50 (3%) had late SA-AKI. Similar proportions were observed when only considering AKI with elevated sCr (71% vs. 3%), severe AKI (67% vs. 6%), or different time windows for early SA-AKI. Compared with early SA-AKI patients, those with late SA-AKI were younger (median age [IQR] 59 [49–70] vs. 69 [58–76] years, p < 0.001), had lower Charlson comorbidity index (3 [1–5] vs. 5 [3–7], p < 0.001) and lower SAPSII scores (41 [34–50] vs. 53 [43–64], p < 0.001). They had similar (24% vs. 26%, p = 0.75) in-hospital mortality. AKI is almost ubiquitous in septic critically ill patients and present within two days of admission. The timing from ICU admission might not be relevant to distinguish different phenotypes of SA-AKI. Ethics Committee Vaud, Lausanne, Switzerland (n°2017-00008). [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested a low potential risk for contrast medium-induced kidney injury in patients with relatively normal renal function. However, whether contrast media cause additional deterioration of renal function in patients with acute kidney injury (AKI), including those with sepsis-associated AKI, remains unclear. This study aimed to evaluate the effect of contrast media on renal function and mortality in patients with sepsis who already had AKI.Methods: We performed a propensity score-matched historical cohort study in the medico-surgical intensive care unit of Jichi Medical University Hospital. Adult patients who were diagnosed with sepsis and AKI were enrolled. Records from our sepsis database from 2011 to 2017 were examined. Septic patients with AKI who received contrast media within 24 h of admission (C group) were matched 1:1 with septic patients who did not receive contrast media (NC group). The primary outcome was deterioration of kidney function (DRF), which was defined as an elevation of serum creatinine levels (> 0.3 mg/dL or 1.5-fold from baseline) or induction of renal replacement therapy.Results: A total of 339 septic patients with AKI were included. After propensity score adjustment, the DRF rate was similar between the C and NC groups (34.0% versus 35.0%; P = 1.00). The 7-day mortality (3.0% versus 6.0%; P = 0.50), 28-day mortality (9.2% versus 15.0%; P = 0.25), and 90-day mortality (25.8% versus 32.1%; P = 0.45) rates were comparable between the two groups. In propensity-adjusted subsets of a high-risk subset (AKI stages 2 and 3 on admission), the rate of DRF was also similar between the two groups.Conclusions: A single administration of contrast media was not associated with exacerbation of AKI or increased short/long-term mortality in patients with sepsis. [ABSTRACT FROM AUTHOR]