Risk factors associated to hospital mortality in patients with acute kidney injury on hemodialysis

Sepsis is a systemic inflammatory state that occurs in response to infection and significantly increases mortality in combination with acute kidney injury (AKI). Macrophages accumulate in the kidney after injury and undergo a transition from a proinflammatory (M1) phenotype to an alternatively activated (M2) phenotype that is required for normal repair. However, the specific signals that regulate the transition from the M1 to M2 phenotype in vivo are unknown. Here, we found an unexpected role of Colony stimulating factor 2 (Csf2) in controlling macrophage transition in vitro and in a mouse model of sepsis induced by cecal ligation and puncture (CLP). We first co-cultured human M1 macrophages with HK-2 cells and characterized cytokine/chemokine profiles via Luminex. Of the cytokines and chemokines that were overexpressed in medium from M1 macrophages cocultured with human kidney-2 (HK-2) cells compared with that from M1 macrophages cultured alone, Csf2 and IL6 showed the greatest increases. Csf2 was exclusively secreted by HK-2 cells but not by M1 macrophages. Furthermore, recombinant human Csf2 protein promoted transition of M1 macrophages to the M2 phenotype in a dose and time-dependent manner. The apoptosis and reactive oxygen species (ROS) release induced by M1 macrophages in HK-2 cells was attenuated after exposure to exogenous Csf2. In addition, the switch from the proinflammatory M1 phenotype to the M2 phenotype occurred via the p-Stat5 pathway, which was activated by Csf2. Importantly, we found that intraperitoneal injection of a Csf2-neutralizing antibody after CLP aggravated kidney injury and suppressed tubular proliferation, subsequently decreasing survival. However, administration of recombinant mouse Csf2 protein could rescue mice with sepsis. Together, our results indicate that Csf2 plays critical roles in regulating macrophage transition via activation of p-STAT5. These data form a foundation upon which new therapeutic strategies can be designed to improve the therapeutic efficacy of cytokine-based treatments for sepsis-induced AKI.

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“…AKI is a global health problem with high morbidity and mortality ( 31 ). Macrophages are highly heterogeneous in terms of origin and function.…”

Section: Discussionmentioning

confidence: 99%

Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition

Zhai

Zhang

et al. 2020

Front. Immunol.

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“…Renal failure is associated with high mortality in critically ill patients, especially patients with septic shock. Several trials have determined ways to predict decreased renal function and to improve clinical outcomes 16–18 . Recently, a new method, using machine leaning, is being studied to develop a prediction algorithm for AKI 19 .…”

Section: Discussionmentioning

confidence: 99%

Optimal timing of initiating continuous renal replacement therapy in septic shock patients with acute kidney injury

Yoon

Leem

Park

et al. 2019

Sci Rep

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Acute kidney injury (AKI) in patients with septic shock is associated with high mortality, but the appropriate timing for initiating continuous renal replacement therapy (CRRT) is controversial. We retrospectively enrolled 158 septic shock patients with AKI in the medical intensive care unit (ICU) from July 2016 to April 2018. The time from AKI onset to CRRT initiation was compared according to ICU mortality using Cox proportional hazard, receiver operating characteristic, and Kaplan-Meier survival analyses. At the time of ICU discharge, the mortality rate was 50.6% (n = 80). It took longer to initiate CRRT in non-survivors than in survivors (hazard ratio 1.009; 95% confidence interval [CI] 1.003–1.014; P = 0.002). The cut-off time from AKI onset to CRRT initiation for ICU mortality was 16.5 hours (area under the curve 0.786; 95% CI 0.716–0.856; P < 0.001). The cumulative mortality rate was significantly higher in patients in whom CRRT was initiated beyond 16.5 hours after AKI onset than in those in whom CCRT was initiated within 16.5 hours (log-rank test, P < 0.001). Several clinical situations must be considered to determine the optimal timing of CRRT initiation in these patients. Close observation and CRRT initiation within 16.5 hours after AKI onset may help improve survival.

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“…[8][9][10] However, it is necessary to point out that these studies used medical records or the International Classification of Diseases (ICD-10) coding to identify patients with AKI, so it is not known which criteria were used to establish the diagnosis. [8][9][10] A study on the basis of the registry of AKI cases reported by MINSA between 2005 and 2016 and the data reported from death certificates during the same period showed that AKI cases increased and AKI-related deaths decreased over time. 7 The agestandardized AKI incidence rate, regardless of severity, increased from 9.6 per 100,000 in 2005 to 14.0 per 100,000 in 2016, and the age-standardized mortality rate decreased from 2.3 per 100,000 in 2005 to 1.2 per 100,000 in 2016 7 (Figure 1).…”

Section: Epidemiology Of Aki In Perumentioning

confidence: 99%

“…Those characteristics include older age, the presence of multiple comorbidities, sepsis as the cause of AKI, and the need for care in intensive care units. [8][9][10] However, it is necessary to point out that these studies used medical records or the International Classification of Diseases (ICD-10) coding to identify patients with AKI, so it is not known which criteria were used to establish the diagnosis. [8][9][10] A study on the basis of the registry of AKI cases reported by MINSA between 2005 and 2016 and the data reported from death certificates during the same period showed that AKI cases increased and AKI-related deaths decreased over time.…”

Section: Epidemiology Of Aki In Perumentioning

confidence: 99%

Global Perspectives in AKI: Peru

2023

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Risk factors associated to hospital mortality in patients with acute kidney injury on hemodialysis

Abstract: Lactate is an objective parameter that can predict prognosis and contributes to a better management of acute kidney injury in hemodialysis patients.

Cited by 5 publications

References 14 publications

Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition

Csf2 Attenuated Sepsis-Induced Acute Kidney Injury by Promoting Alternative Macrophage Transition

Optimal timing of initiating continuous renal replacement therapy in septic shock patients with acute kidney injury

Global Perspectives in AKI: Peru

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