scholarly journals ATRvD1 Attenuates Renal Tubulointerstitial Injury Induced by Albumin Overload in Sepsis-Surviving Mice

2021 ◽  
Vol 22 (21) ◽  
pp. 11634
Author(s):  
José Bruno N. F. Silva ◽  
Thayanne B. B. Calcia ◽  
Cyntia P. Silva ◽  
Rafael F. Guilherme ◽  
Fernando Almeida-Souza ◽  
...  

Novel strategies for the prevention and treatment of sepsis-associated acute kidney injury and its long-term outcomes have been required and remain a challenge in critical care medicine. Therapeutic strategies using lipid mediators, such as aspirin-triggered resolvin D1 (ATRvD1), can contribute to the resolution of acute and chronic inflammation. In this study, we examined the potential effect of ATRvD1 on long-term kidney dysfunction after severe sepsis. Fifteen days after cecal ligation and puncture (CLP), sepsis-surviving BALB/c mice were subjected to a tubulointerstitial injury through intraperitoneal injections of bovine serum albumin (BSA) for 7 days, called the subclinical acute kidney injury (subAKI) animal model. ATRvD1 treatment was performed right before BSA injections. On day 22 after CLP, the urinary protein/creatinine ratio (UPC), histologic parameters, fibrosis, cellular infiltration, apoptosis, inflammatory markers levels, and mRNA expression were determined. ATRvD1 treatment mitigated tubulointerstitial injury by reducing proteinuria excretion, the UPC ratio, the glomerular cell number, and extracellular matrix deposition. Pro-fibrotic markers, such as transforming growth factor β (TGFβ), type 3 collagen, and metalloproteinase (MMP)-3 and -9 were reduced after ATRvD1 administration. Post-septic mice treated with ATRvD1 were protected from the recruitment of IBA1+ cells. The interleukin-1β (IL-1β) levels were increased in the subAKI animal model, being attenuated by ATRvD1. Tumor necrosis factor-α (TNF-α), IL-10, and IL-4 mRNA expression were increased in the kidney of BSA-challenged post-septic mice, and it was also reduced after ATRvD1. These results suggest that ATRvD1 protects the kidney against a second insult such as BSA-induced tubulointerstitial injury and fibrosis by suppressing inflammatory and pro-fibrotic mediators in renal dysfunction after sepsis.

Author(s):  
José Bruno N. F. Silva ◽  
Thayanne B. B. Calcia ◽  
Cyntia P. Silva ◽  
Rafael F. Guilherme ◽  
Fernando Almeida-Souza ◽  
...  

Current interventions are not effectives in preventing sepsis-induced acute kidney injury and its long-term outcomes or even after second renal insult. Therapeutic strategies using lipid mediators, as aspirin-triggered resolvin D1 (ATRvD1), can contribute for resolution of acute and chronic inflammation. In this study, we examined the potential effect of ATRvD1 on long-term kidney dysfunction after severe sepsis. Fifteen days after cecal ligation and puncture (CLP), sepsis-surviving BALB/c mice were subjected to a tubulointerstitial injury through intraperitoneal injections of bovine serum albumin (BSA) for 7 days, called subclinical acute kidney injury (subAKI) animal model. ATRvD1 treatment was performed right before BSA injections. On day 22 after CLP, urinary protein/creatinine ratio (UPC), histologic parameters, fibrosis, cellular infiltration, apoptosis, inflammatory markers levels, and mRNA expression were determined. ATRvD1 treatment mitigated tubulointerstitial injury by reducing the proteinuria excretion, UPC ratio, glomerular cell number and extracellular matrix deposition. Pro-fibrotic markers, as transforming growth factor β (TGFb), type 3 collagen and metalloproteinase (MMP)-3 and -9 were reduced after ATRvD1 administration. Post-septic mice treated with ATRvD1 were protected from renal apoptosis and recruitment of F4/80+ cells. Interleukin-1b (IL-1b) levels were increased in subAKI animal model, being attenuated by ATRvD1. Tumor necrosis factor-a (TNF-a), IL-10 and IL-4 mRNA expression was increased in the kidney of BSA-challenged post-septic mice and it was also reduced after ATRvD1. These results suggest that ATRvD1 protects the kidney against a second insult as BSA-induced tubulointerstitial injury and fibrosis by suppressing inflammatory and pro-fibrotic mediators in renal dysfunction after sepsis.


2020 ◽  
Author(s):  
P S Priyamvada ◽  
Challa Jaswanth ◽  
Bobby Zachariah ◽  
Satish Haridasan ◽  
Sreejith Parameswaran ◽  
...  

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Gianluca Villa ◽  
Silvia De Rosa ◽  
Caterina Scirè Calabrisotto ◽  
Alessandro Nerini ◽  
Thomas Saitta ◽  
...  

Abstract Background Postoperative acute kidney injury (PO-AKI) is a leading cause of short- and long-term morbidity and mortality, as well as progression to chronic kidney disease (CKD). The aim of this study was to explore the physicians’ attitude toward the use of perioperative serum creatinine (sCr) for the identification of patients at risk for PO-AKI and long-term CKD. We also evaluated the incidence and risk factors associated with PO-AKI and renal function deterioration in patients undergoing major surgery for malignant disease. Methods Adult oncological patients who underwent major abdominal surgery from November 2016 to February 2017 were considered for this single-centre, observational retrospective study. Routinely available sCr values were used to define AKI in the first three postoperative days. Long-term kidney dysfunction (LT-KDys) was defined as a reduction in the estimated glomerular filtration rate by more than 10 ml/min/m2 at 12 months postoperatively. A questionnaire was administered to 125 physicians caring for the enrolled patients to collect information on local attitudes regarding the use of sCr perioperatively and its relationship with PO-AKI. Results A total of 423 patients were observed. sCr was not available in 59 patients (13.9%); the remaining 364 (86.1%) had at least one sCr value measured to allow for detection of postoperative kidney impairment. Among these, PO-AKI was diagnosed in 8.2% of cases. Of the 334 patients who had a sCr result available at 12-month follow-up, 56 (16.8%) developed LT-KDys. Data on long-term kidney function were not available for 21% of patients. Interestingly, 33 of 423 patients (7.8%) did not have a sCr result available in the immediate postoperative period or long term. All the physicians who participated in the survey (83 out of 125) recognised that postoperative assessment of sCr is required after major oncological abdominal surgery, particularly in those patients at high risk for PO-AKI and LT-KDys. Conclusion PO-AKI after major surgery for malignant disease is common, but clinical practice of measuring sCr is variable. As a result, the exact incidence of PO-AKI and long-term renal prognosis are unclear, including in high-risk patients. Trial registration ClinicalTrials.gov, NCT04341974.


Author(s):  
Sidharth Kumar Sethi ◽  
Rajesh Sharma ◽  
Aditi Gupta ◽  
Abhishek Tibrewal ◽  
Romel Akole ◽  
...  

Author(s):  
John R. Prowle ◽  
Lui G. Forni ◽  
Max Bell ◽  
Michelle S. Chew ◽  
Mark Edwards ◽  
...  

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.


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