scholarly journals Evaluation of peptidylarginine deiminase 4 and PADI4 polymorphisms in sepsis-induced acute kidney injury

2020 ◽  
Vol 66 (11) ◽  
pp. 1515-1520
Author(s):  
Nara Aline Costa ◽  
Bertha Furlan Polegato ◽  
Amanda Gomes Pereira ◽  
Sérgio Alberto Rupp de Paiva ◽  
Ana Lúcia Gut ◽  
...  

SUMMARY BACKGROUND: The aim of this study is to evaluate the peptidylarginine deiminase 4 (PAD 4) concentration and PADI4 polymorphisms as predictors of acute kidney injury (AKI) development, the need for renal replacement therapy (RRT), and mortality in patients with septic shock. METHODS: We included all individuals aged ≥ 18 years, with a diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentration and its PADI4 polymorphism (rs11203367) and (rs874881). Patients were monitored during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and the need for RRT were also evaluated. RESULTS: There were 99 patients, 51.5% of whom developed SAKI and of these, 21.5% needed RRT and 80% died in the ICU. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. CONCLUSION: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients.

2019 ◽  
Author(s):  
Nara Aline Costa ◽  
Bertha Furlan Polegato ◽  
Amanda Gomes Pereira ◽  
Rodrigo Velloni da Silva Bastos ◽  
Sérgio Alberto Rupp de Paiva ◽  
...  

Abstract Background: The influence of PAD4 concentration and its polymorphisms in SAKI development are poorly evaluated. Thus, the aim of this study is to evaluate the PAD 4 concentration and PADI4 polymorphisms, as predictors of AKI development, need for renal replacement therapy (RRT), and mortality in patients with septic shock. Methods: We included all individuals aged ≥ 18 years, with the diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient’s admission to determine serum PAD4 concentration and its polymorphism PADI4 (rs11203367) and (rs874881). Patients were followed during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and need for RRT were also evaluated. Results: 99 patients were included in the analysis. SAKI developed in approximately 51.5% of patients during the ICU stay; of these, 21.5% required RRT and 80% died. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. Conclusion: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients.


2021 ◽  
Vol 18 (4) ◽  
pp. 80-89
Author(s):  
T. G. Kim ◽  
M. А. Magomedov ◽  
D. N. Protsenko ◽  
M. V. Zakharov ◽  
А. V. Marukhov ◽  
...  

Of all cases of acute kidney injury (AKI), 45-70% are associated with sepsis. Lethality in sepsis-associated AKI requiring renal replacement therapy (RRT) ranges from 40 to 50%, and in AKI combined with other organ dysfunctions - 60-80%. In order to improve the results of treatment of sepsis and septic shock, various methods of extracorporeal detoxification (ECD) have been developed. The effectiveness of these methods is controversial. In the treatment of sepsis, RRT is used not only to replace the impaired detoxification function of kidneys, but also to remove excess cytokines from the systemic bloodstream. The literature describes mainly positive results of the use of dialyzers with an adsorbing membrane, however, these data do not have the necessary degree of evidence. Currently, there are no clear criteria for the initiation of RRT, its duration and doses, the choice of methodology determined by specific clinical and laboratory parameters, and staging of this therapy. All this highlights the need for further research in this field.


Burns ◽  
2020 ◽  
Vol 46 (1) ◽  
pp. 190-198 ◽  
Author(s):  
Filippo Mariano ◽  
Zsuzsanna Hollo’ ◽  
Nadia Depetris ◽  
Valeria Malvasio ◽  
Alberto Mella ◽  
...  

2020 ◽  
Author(s):  
Fang Liu ◽  
Jing Zhang ◽  
Yuan Zhu ◽  
Lianjiu Su ◽  
Yiming Li ◽  
...  

Abstract Background: The previous study demonstrated that there were no significant differences between saline and balanced crystalloid solution infused in critical illness. However, the sepsis subgroup analysis showed the statistical difference. Thus, we will specifically focus on septic patients in this study to compare the effects of saline and balanced solution. We hypothesize that effects of saline on acute kidney injury (AKI) are related to the underline AKI severity and total volumes of infusion. Methods/design: The investigators designed a pragmatic, multi-centered crossover trial recruiting 312 patients who are diagnosed as sepsis/septic shock in the intensive care unit (ICU) and will be assigned with either acetate Ringer's solution or saline in the corresponding month. Patients with an end-stage renal disease (ESRD) or who need renal replacement therapy (RRT) prior to or at the time of enrollment are excluded. Enrolled patients will be regarded as with mild, moderate or severe sepsis on the basis of the severity of their illness, and will be divided into subgroups according to their initial renal function and various intravenous infusion volumes when being analyzed. The primary outcome is major adverse kidney events (MAKE), including the composite of in-hospital death, receipt of new renal replacement therapy, or persistent renal dysfunction. Secondary outcomes include 28 days-mortality, internal environment disturbance, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, duration of RRT and ICU and hospital length of stay. Results and Conclusions: To our knowledge, this study will be the first to focus on septic patients and provide credible and evident data on the comparison of outcome between acetate Ringer’s solution and saline for intravenous infusion in adult septic patients on the basis of baseline renal function and infusion volumes taken into consideration. Trial registration: ClinicalTrials.gov, identifiers: NCT03685214. Registered on August 15, 2018. https://clinicaltrials.gov/ct2/show/NCT03685214 Keywords: sepsis; septic shock; acute kidney injury; saline; acetate Ringer's solution.


2019 ◽  
Vol 43 (1) ◽  
pp. 10-16
Author(s):  
Thomas Dimski ◽  
Timo Brandenburger ◽  
Torsten Slowinski ◽  
Detlef Kindgen-Milles

Introduction: Septic shock is characterized by severe metabolic and hemodynamic alterations. It is often accompanied by acute kidney injury. A new adjunct treatment is hemoadsorption using a cytokine adsorber in line with continuous veno-venous renal replacement therapy. We studied the feasibility, efficacy, and safety of cytokine adsorption with citrate-anticoagulated continuous veno-venous hemodialysis (regional citrate anticoagulation–continuous veno-venous hemodialysis). Methods: In 11 patients with septic shock and acute kidney injury stage 3, we studied 12 cycles of cytokine adsorption and regional citrate anticoagulation–continuous veno-venous hemodialysis. We monitored parameters of citrate anticoagulation, circuit lifetime, laboratory parameters, hemodynamics, and vasopressor demand. Results: Ten out of 12 adsorber/continuous veno-venous hemodialysis circuits reached the target lifetime of 24 h for the adsorber. One system clotted and one was stopped for non-device-related reasons. Nine of the remaining continuous renal replacement therapy circuits reached 72 h lifetime. With default settings for regional citrate anticoagulation, serum ionized calcium and pH were in the normal range. Urea and creatinine were reduced significantly, and norepinephrine dose decreased from 0.47 (±0.09) to 0.16 (±0.04) µg/kg/min ( p = 0.016) after 24 h. Discussion: We show that combined cytokine adsorption/continuous veno-venous hemodialysis is effective to control pH, to reduce urea and creatinine, and to improve hemodynamics by reducing norepinephrine doses in patients with septic shock. It can be applied safely with standard settings of regional citrate anticoagulation rendering sufficiently long filter lifetimes for the adsorber and the continuous veno-venous hemodialysis circuit. Further studies are on the way to investigate whether these effects translate into improved outcomes in septic shock patients.


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