scholarly journals The role of hepatocellular death and systemic inflammation in the development of acute kidney injury in acute decompensation of alcoholic liver cirrhosis

Author(s):  
A. S. Rodina ◽  
M. E. Shubina ◽  
I. V. Kurbatova ◽  
L. V. Topchieva ◽  
O. P. Dudanova

The aim of the study was to assess the role of hepatocellular death and systemic inflammation in the development of acute kidney injury (AKI) in acute decompensation of alcoholic liver cirrhosis (AD ALC).Materials and methods. 125 patients with ALC were examined: 20 (16.0%) (group I) with signs of hepatorenal syndromeacute kidney injury (HRS-AKI) at the age of 57.13 ± 9,08 years, 13 men (65.0%) and 105 (84.0%) patients (group II) without such a syndrome at the age of 56.30 ± 9.6 years., 62 men (59.0%). Along with liver tests, a markers of hepatocyte apoptosis and cytokines were determined by ELISA: fragments of cytokeratin-18 (FCK-18) ("Biotech" Sweden), cytokines — TNF-α, IL-1β, IL-4, IL-6, IL-8 (“Vector-Best”, Russia). Grade and index of acute on chronic liver failure (ACLF) were determined using an on-line calculator (www.efclif.com/scientific-activity/score-calculators/clif-c-aclf).Results. The hepatocellular death indicators were significantly higher in patients of group I with HRS-AKI compared with patients of group II without HRS-AKI: FCK-18-1609.44 ± 542.79 U / l versus 975.77±607.59 U / l, bilirubin — 242.64 ± 98.14 pmol/l versus 145.09 ± 79.35 pmol/l, inflammation indicators — TNF-α — 9.28 ± 3,11 pg/ml versus 6.59 ± 2.21 pg/ml, IL-6-54.79 ± 17.7 pg/ml versus 36.71 ± 18.05 pg/ml, CRP — 49.68 ± 23.23 mg/l versus 22.07 ± 20.40 mg/l, leukocytes — 12.23 ± 3.28x109/l versus 8,66 ± 2,31x109/l (everywhere p <0.05). ACLF developed in all (100.0%) patients of group I, its grade was 2.73±0.76 and score — 56.33 ± 4.01; ACLF developed only in 37 (35,2%) patients of group II, its grade was1.05±0.24 (p<0,05) and score was 47.45 ± 4,80 (p <0.05).Conclusion. The development of HRS-AKI in patients with acute decompensation of ALC was associated with significantly higher rates of hepatocytic apoptosis, hyperbilirubinemia, systemic inflammation, frequency and severity of ACLF.

2016 ◽  
Vol 19 (3) ◽  
pp. 123 ◽  
Author(s):  
Orhan Findik ◽  
Ufuk Aydin ◽  
Ozgur Baris ◽  
Hakan Parlar ◽  
Gokcen Atilboz Alagoz ◽  
...  

<strong>Background:</strong> Acute kidney injury is a common complication of cardiac surgery that increases morbidity and mortality. The aim of the present study is to analyze the association of preoperative serum albumin levels with acute kidney injury and the requirement of renal replacement therapy after isolated coronary artery bypass graft surgery (CABG).<br /><strong>Methods:</strong> We retrospectively reviewed the prospectively collected data of 530 adult patients who underwent isolated CABG surgery with normal renal function. The perioperative clinical data of the patients included demographic data, laboratory data, length of stay, in-hospital complications and mortality. The patient population was divided into two groups: group I patients with preoperative serum albumin levels &lt;3.5 mg/dL; and group II pateints with preoperative serum albumin levels ≥3.5 mg/dL.<br /><strong>Results:</strong> There were 413 patients in group I and 117 patients in group II. Postoperative acute kidney injury (AKI) occured in 33 patients (28.2%) in group I and in 79 patients (19.1%) in group II. Renal replacement therapy was required in 17 patients (3.2%) (8 patients from group I; 9 patients from group II; P = .018). 30-day mortality occurred in 18 patients (3.4%) (10 patients from group I; 8 patients from group II; P = .037). Fourteen of these patients required renal replacement therapy. Logistic regression analysis revealing the presence of lower serum albumin levels preoperatively was shown to be associated with increased incidence of postoperative AKI (OR: 1.661; 95% CI: 1.037-2.661; <br />P = .035). Logistic regression analysis also revealed that DM (OR: 3.325; 95% CI: 2.162-5.114; P = .000) was another independent risk factor for AKI after isolated CABG. <br /><strong>Conclusion:</strong> Low preoperative serum albumin levels result in severe acute kidney injury and increase the rate of renal replacement therapy and mortality after isolated CABG.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xudong Wang ◽  
Yali Wang ◽  
Mingjian Kong ◽  
Jianping Yang

Abstract Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.


Author(s):  
T.P. Borysova ◽  
◽  
O.U. Obolonska ◽  
◽  

Nephrogenesis may be disrupted antenatally because of chronic infection foci (CIF) in the mother, the development of chorioamnionitis, feto-placental insufficiency. As a result, in the postnatal period, the kidneys are more sensitive to hypoperfusion, which occurs in premature infants with hemodynamically significant patent ductus arteriosus (HSPDA) and can lead to the development of acute kidney injury (AKI). Purpose — to study the influence of CIF in the mother on the development of AKI in premature infants with HSPDA. Materials and methods. 74 premature infants (gestational age 29–36 weeks) who were treated in the Department of Anesthesiology and Neonatal Intensive Care MI «Dnepropetrovsk Regional Children's Clinical Hospital» Dnepropetrovsk Regional Council» were examined. Patients were divided into three groups depending on the presence of a patent ductus arteriosus (PDA) and its hemodynamic significance: Group I — 40 children with HSPDA, Group II — 17 children with PDA without hemodynamic disorders, Group III — 17 children with a closed ductus arteriosus. The presence of CIF in the mother was determined according to medical records, chorioamnionitis on the basis of histopathological examination of the placenta. Patients with HSPDA were divided into two subgroups: 28 children from mothers with CIF, 12 — without CIF. Clinical examination and treatment of premature infants was carried out according to generally accepted methods. Echocardiography with Doppler was performed at 5–11 hours of life and then daily to determine PDA, its size and hemodynamic significance. Diagnosis and stratification of the severity of AKI were performed according to the criteria of neonatal modification of KDIGO, for which the concentration of serum creatinine and diuresis were studied. Results. Chronic foci of infection were found in 28 (70.0%) mothers of group I, in 5 (29.4%) — group II, in 6 (35.2%) — group III. Chorioamnionitis in group I — 10 (25%) cases, in group II–ІII — 6 (17.6%). The presence of CIF in the mother caused a significant increase in the size of the PDA on the first day of life in the group of HSPDA against groups II–III: 2.61±0.861 (2.3; 2–3.5) mm against 1.79±0.365 (1.7; 1.5–2) mm, p<0.001. Patent arterial duct with a diameter of >2 mm on the first day of life in premature infants of group I from mothers with foci of infection was observed more often — 19 (67.9%) against 2(6.7%) of groups II–III (OR=10.56; CI: 1.9–58.53, p<0.005). Analysis of the incidence of AKI on the third day of life depending on HSPDA and the presence of CIF showed that 64.3% of preterm infants with HSPDA and maternal infection developed AKI — 6.6 times more often than in groups without HSPDA (OR=8.40; CI: 2.60–27.14; p<0.001), and 2.6 times more often compared to children of the subgroup HSPDA without recorded maternal infection (OR=5.40; CI: 1.18–24.65; p<0.03). On the background of HSPDA and CIF stage II–III AKI was observed in every third child. Comparative analysis within group I depending on the CIF revealed that the frequency of AKI for 10 days in the subgroup with infection was almost three times higher than the level of the subgroup without infection: 71.4% vs. 25.0% (OR=7.50; CI: 1.60–35.07; p<0.009). Conclusions. The presence of CIF in the mother is a risk factor for AKI in premature infants with HSPDA. Therefore, such children should be classified as at risk of developing AKI. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: acute kidney injury, chronic foci of maternal infection, hemodynamically significant patent ductus arteriosus, premature infants.


2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Lyne Gagnon ◽  
Jean-Francois Thibodeau ◽  
Chet Holterman ◽  
Marie-Pier Cloutier ◽  
Jean-Christophe Simard ◽  
...  

2018 ◽  
Vol 11 (1) ◽  
pp. 59-66
Author(s):  
Md Mosharul Haque ◽  
M Atahar Ali ◽  
Mustafizul Aziz ◽  
Mohammad Ullah ◽  
Mohammad Anowar Hossain ◽  
...  

Background: Acute kidney injury (AKI) is a risk factor for long-term adverse outcomes, including acute myocardial infarction and death. The objective of this study was to find out in-hospital outcomes in patients with acute ST elevation myocardial infarction with acute kidney injury.Methods: A total 190 patients were included in this study and were equally divided into two groups, Group-I (with AKI) and Group-II (without AKI), according to absolute changes of serum creatinine level. AKI was defined as absolute changes in serum creatinine (SCr. at 48 hours’ minus admission SCr) and categorized as mild AKI (increase of 0.3 to <0.5 mg/d), moderate AKI (increase of 0.5 to <1.0 mg/dl), and severe AKI (increase of e”1.0 mg/dl) using Acute Kidney Injury Network (AKIN) criteria.Results: Overall in-hospital mortality rate was 14.7% in Group-I (mortality rate for those with mild, moderate, and severe AKI were 7%, 13.3%, and 31.8%) compared with 5.3% in Group-II. Regarding inhospital morbidities, significant arrhythmia (29.5%) was the most common complication followed by acute heart failure (18.9%), cardiogenic shock (12.6%), and mechanical complications (4.2%) which were more in Group-I compared to patients with Group-II. After adjustment of other risk variables, the multivariate logistic regression analysis revealed AKI remained an independent predictor of in-hospital mortality with adjusted odds ratios (OR) was 4.991 (95% confidence interval, 1.873-13.301).Conclusions: AKI is an independent predictor of in-hospital mortality and morbidity. It emphasizes the importance of efforts to identify risk factors and to prevent AKI during in-hospital management of acute STEMI patients.Cardiovasc. j. 2018; 11(1): 59-66


2016 ◽  
Vol 101 (7-8) ◽  
pp. 390-398
Author(s):  
Kursad Oz ◽  
Safa Gode ◽  
Serdar Basgoze ◽  
Murat Koser ◽  
Atilla Oz ◽  
...  

Acute kidney injury (AKI) is associated with cardiovascular mortality and morbidity especially in high-risk patients undergoing cardiac surgery. It ranges from 7.7% to 28.1% in different studies. The aim of this study was to compare cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) with Creatinine as an early marker for acute kidney injury in geriatrics. From 2013 through 2015, 307 consecutive high-risk elderly patients older than 70 years undergoing emergency coronary artery bypass grafting using extracorporeal circulation were studied. All patients underwent diagnostic coronary angiography and the surgical procedure within 1 week in single hospital stay and were randomized according to timing of interval between coronary angiographyand cardiac procedure as follows: group I, less than 2 days; group II, between 2 and 4 days; and group III, higher than 4 days. Renal function was analyzed by serum cystatin C, NGAL, and creatinine. Blood samples were obtained from each patient at five time points: basal value before operation, in the four hours after operation, and on the first, third, and fifth postoperative days. Glomerular filtration rate (GFR) was calculated by Cockcroft-Gault (CG). A total of 56 patients developed postoperative acute kidney failure according to the risk, injury, and failure; and loss; and end-stage kidney disease classification. Perioperative fluid requirements, urine output, and vasopressor need during and after cardiopulmonary bypass were similar. 30-day mortality in groups was higher in group I than group II and group III (P = 0.025). AKI was least prominent in group III compared to group I and group II (P = 0.001) and expectedly, postoperative dialysis requirement was least common in group III (15, 16.66%). Patients in group III had the most favorable clinical outcome with regards to the length of ICU and hospital stay. Overall serum creatinine, cystatin C, and urine NGAL levels changed significantly throughout the entire length of following-up period in group I and group II, but not in group III. Changes in serum levels of cystatin, creatinine, and creatinine clearance were prominent in later than 24 hours. Urinary NGAL was the first variable to rise in the immediate postoperative period. Cystatin GFR was a more rapid marker than serum creatinine GFR to show acute kidney injury in three groups was a significant marker.


Author(s):  
Ferdiansyah Mahyudin ◽  
Mouli Edward ◽  
Muhammad Hardian Basuki ◽  
Kadek Seta Prawira

Background: Osteosarcoma is a malignant bone disease. Predictors which used to determine osteosarcoma from non-invasive (stage IIB) to invasive (stage III), through the ratio of macrophages-1 (M-1) which are pro-inflammatory (anti-cancer) with macrophages-2 (M-2) which have anti-inflammatory characteristic (pro cancer) is not clear yet.Purpose: To elaborate the role of M-1 ratio with M-2 in the development of non-invasive osteosarcoma become invasive, in effort to obtain predictors that can be used to the selection of neoadjuvant therapy time.Methods: An observational study with cross sectional analytic study design. The sample of this research were all of paraffin blocks containing osteosarcoma patient tissue, collected within 5 years. The number of samples that met the inclusion criteria was 26 samples, and then divided into two groups, namely group-I as many as 13 stages IIB and group-II as many as 13 samples of stage III. The measured variables are the number of macrophages that express TNF-α and those that express IL-10 by immunohistochemical methods.Results: Analysis of the data using a Mann-Whitney test, and the results were obtain is the number of macrophages expressing TNF-α in group-I was greater than in group-II (p <0.05). Likewise, macrophages that expressed IL-10 in group I were smaller than in group-II (p <0.05).Conclusion: The M-1 ratio which reflected by TNF-α expression cells with M-2 as reflected by IL-10 expression cells in the non-invasive group is 5: 1.Whereas in the group that develops to invasive is 1:6.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yingying Zhang ◽  
Chen Yu

Abstract Background and Aims Macrophages are key inflammatory cells and play a critical role in renal inflammation in acute kidney injury (AKI). M1 inflammatory macrophage and M2 anti-inflammatory macrophage act reverse role. Phenotype of macrophages is highly flexible and can be changed over time. However, the underlying mechanism of M1 and M2 macrophage phenotype switching during AKI is still largely unclear. In our previous study, we identified a novel lncRNA (LRNA9884) might contribute to inflammation according to modifying macrophages. The present study was designed to uncover the pathogenic role and the underlying mechanism of LRNA9884 in cisplatin-induced AKI. Method Expression level and pattern of LRNA9884 were examined in cisplatin-induced AKI mice. The regulatory mechanisms of LRNA9884 was investigated in cultured bone marrow–derived macrophages (BMDMs) in vitro by silencing or overexpressing of LRNA9884. Flow Cytometer, fluorescence in situ hybridization (FISH) and other multiple molecular biological techniques were applied to figure out the role of LRNA9884 under acute kidney injury. Results LRNA9884 was significantly upregulated in the kidney of cisplatin-induced mice and was associated with the progression of the renal inflammation by using RT-PCR and ISH assay. FISH assay with immunofluorescence co-staining detected that LRNA9884 was largely expressed in the nucleus of macrophage in cisplatin-induced mice kidney compared with the sham group at day 1 after AKI injury. LRNA9884 was remarkedly induced by TNF-α (10ng/ml) in BMDMs as time- and dose- dependent. Western blot and RT-PCR showed that silencing of LRNA9884 effectively inhibited upregulated of macrophage-inducible C-type lectin (Mincle) and iNOS induced by TNF-α. More importantly, we identified that LRNA9884 maintained M1 macrophages phenotype by triggering mincle production at transcriptional level as evidenced by ChIP assay. Conclusion LRNA9884 is a mincle-dependent lncRNA that highly-expressed in macrophages under AKI development. Targeting of LRNA9884 effectively blocked the inflammatory response via promoting the transition M1 macrophage to M2 macrophage phenotype. This study will shed new lights on the understanding of pathological role of novel LRNA9884 in AKI.


2012 ◽  
Vol 302 (9) ◽  
pp. F1104-F1111 ◽  
Author(s):  
Steven Yap ◽  
Sang Won Park ◽  
Brian Egan ◽  
H. Thomas Lee

Acute kidney injury frequently occurs in the critically ill and often progresses into multiorgan dysfunction syndrome, resulting in high mortality. We previously showed that nephrectomized mice had increased interleukin (IL)-6 and tumor necrosis factor (TNF)-α that directly contributed to systemic inflammation and hepatic injury. In this study, we examined whether patients undergoing laparoscopic donor nephrectomy have increased postoperative cytokine levels with injury to the liver and whether the remaining kidney sustains injury. Serial serum and urine samples were collected from 32 patients undergoing laparoscopic donor nephrectomy and 17 patients undergoing nonrenal laparoscopic surgery. Serum IL-6, IL-18, TNF-α and monocyte chemotactic protein-1 (MCP-1) (markers of systemic inflammation) and urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), MCP-1, and IL-18 (markers of acute kidney injury) were quantified by enzyme-linked immunosorbent assay. We also analyzed serum creatinine, aspartate transaminase (AST), and alanine transaminase to assess liver injury. Patients who underwent donor nephrectomy not only demonstrated increased serum creatinine but also had significant increases in serum IL-6, MCP-1, and AST. Serum TNF-α also trended upward in donor nephrectomy patients. Finally, the donor nephrectomy group showed increased urinary NGAL but not KIM-1 at 24 h. Taken together, our findings of increased serum IL-6, MCP-1, and AST after donor nephrectomy suggest that an acute reduction of kidney function induces systemic inflammation and may have distant effects on the liver. Further studies are needed to correlate increased urinary NGAL after donor nephrectomy both as a potential marker for renal tubular stress and/or hypertrophy in the contralateral kidney.


2018 ◽  
Vol 22 (6) ◽  
pp. 56-63
Author(s):  
A. V. Siverina ◽  
E. A. Skorodumova ◽  
V. A. Kostenko ◽  
L. P. Pivovarova ◽  
M. E. Malyshev ◽  
...  

THE AIM:to assess the effect of APOE and SLCO1B1 gene polymorphism on the course of myocardial infarction (MI) associated with acute kidney injury (AKI) in hospital and long-term periods.PATIENTS AND METHODS:132 patients with МI were examined, which were divided into 2 groups: the first (I) – 68 patients with MI and AKI, the second (II) – 64 people with MI without AKI.RESULTS:In the distribution of genotypes, polymorphism of Leu28Pro of the APOE gene in the studied groups was revealed that LeuPro was more often inherited in patients of group I – 20,6 %, the average value of total cholesterol (TC) – 6,01±0,3 mmol/l, and low density lipoproteins (LDL) – 3,37±0,21 mmol/l, compared with patients of group II, where the LeuPro genotype – 6, 2 %, TC – 5,03±0,3 mmol/l, LDL – 2,38±0,3 mmol/l, p<0,05. A similar situation was typical for the polymor phism Val174Ala SLCO1B1 gene, where ValAla in patients of group I-26,5 %, in II-12,5 %, p<0.05. In heterozygotes I sample TC-5,59±0,3 mmol/l, and LDL – 3,30±0,14 mmol/l, in group II TC – 5,19±0,29 mmol/l, LDL – 2,75±0,23 mmol / l, p<0,05. The clinical picture of the hospital period in patients with MI and AKI, proceeded with the development of a greater number of complications, which reflected in the high mortality in group I – 16,2 %, in group II – 4,7 %, p<0,05. In the posthospital period, against the background of atorvastatin administration in both study groups, there was a positive trend of decrease in TC and LDL, but it was not possible to achieve the targets. Mortality in the long-term period in group I – 15,4 %, in group II-2,0 %, p<0.05.CONCLUSIONS:in patients with MI and AKI on the background of a more severe clinical course of the disease, both in hospital and in the long-term period, rare allelic variants of the genes APOE and SLCO1B1 were more often determined, which negatively affected the lipid profile.


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