Acute kidney stress--a useful term based on evolution in the understanding of acute kidney injury.
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ABSTRACT:
SUBMITTER: Katz N
PROVIDER: S-EPMC4722620 | biostudies-other | 2016 Jan
REPOSITORIES: biostudies-other
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Project description:BackgroundCisplatin is a commonly used chemotherapeutic agent that has a major limitation because of its nephrotoxicity. We have demonstrated that cisplatin down-regulates the expression of the taurine transporter gene (TauT) in renal cells and that forced overexpression of TauT protects against cisplatin-induced apoptosis in renal cells in vitro and in vivo. In the present study, we have investigated how TauT is regulated by p53 and c-Jun and its role during acute kidney injury (AKI).MethodsRegulation of TauT by p53 and c-Jun was determined by reporter gene assay, DNA binding, Western blot analysis, and immunohistochemistry.ResultsTauT was down-regulated by p53 and up-regulated by c-Jun. Two potential binding sites for c-Jun were identified in the promoter region of TauT. Inhibition of c-Jun N-terminal kinase (JNK) enhanced TauT promoter activity. Overexpression of TauT protects against cisplatin-induced kidney injury in a TauT transgenic mouse model.ConclusionsOur findings suggest that TauT plays a critical role in renal function. Expression of TauT is negatively regulated by p53 and positively regulated by c-Jun, which is mediated by the JNK signaling pathway. The outcome level of TauT may determine the fate of renal cells during stress-induced AKI.
| S-EPMC2994381 | biostudies-literature
Project description:AKI-dialysis patients had a higher incidence of long-term ESRD and mortality than the patients without AKI. The patients who recovered from dialysis were associated with a lower incidence of long-term ESRD and mortality than in the patients who still required dialysis.
| S-EPMC4145550 | biostudies-literature
Project description:Acute kidney injury (AKI) associates with higher in-hospital mortality, but whether it also associates with increased long-term mortality is unknown, particularly after accounting for residual kidney function after hospital discharge. We retrospectively analyzed data from US veteran patients who survived at least 90 d after discharge from a hospitalization. We identified AKI events not requiring dialysis from laboratory data and classified them according to the ratio of the highest creatinine during the hospitalization to the lowest creatinine measured between 90 d before hospitalization and the date of discharge. We estimated mortality risks using multivariable Cox regression models adjusting for demographics, comorbidities, medication use, primary diagnosis of admission, length of stay, mechanical ventilation, and postdischarge estimated GFR (residual kidney function). Among the 864,933 hospitalized patients in the study cohort, we identified 82,711 hospitalizations of patients with AKI. In the study population of patients who survived at least 90 d after discharge, 17.4% died during follow-up (AKI 29.8%, without AKI 16.1%). The adjusted mortality risk associated with AKI was 1.41 (95% confidence interval [CI] 1.39 to 1.43) and increased with increasing AKI stage: 1.36 (95% CI 1.34 to 1.38), 1.46 (95% CI 1.42 to 1.50), and 1.59 (95% CI 1.54 to 1.65; P < 0.001 for trend). In conclusion, AKI that does not require dialysis associates with increased long-term mortality risk, independent of residual kidney function, for patients who survive 90 d after discharge. Long-term mortality risk is highest among the most severe cases of AKI.
| S-EPMC2834549 | biostudies-literature
Project description:Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI.
| S-EPMC4931708 | biostudies-literature
Project description:We previously showed that SerpinA3K is present in urine from rats and humans with acute kidney injury (AKI) and chronic kidney disease (CKD). However, the specific role of SerpinA3K during renal pathophysiology is unknown. To begin to understand the role of SerpinA3K on AKI, SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing ischemia/reperfusion (I/R) and compared to wild type (WT) mice. Four groups were studied: WT+S, WT+IR, KOSA3+S, and KOSA3+IR. As expected, I/R increased serum creatinine and BUN, with a GFR reduction in both genotypes; however, renal dysfunction was ameliorated in the KOSA3+IR group. Interestingly, the increase in UH2O2 induced by I/R was not equally seen in the KOSA3+IR group, an effect that was associated with the preservation of antioxidant enzymes' mRNA levels. Additionally, FOXO3 expression was initially greater in the KOSA3 than in the WT group. Moreover, the increase in BAX protein level and the decrease in Hif1a and Vegfa induced by I/R were not observed in the KOSA3+IR group, suggesting that these animals have better cellular responses to hypoxic injury. Our findings suggest that SerpinA3K is involved in the renal oxidant response, HIF1α/VEGF pathway, and cell apoptosis.
| S-EPMC10177890 | biostudies-literature
Project description:Background Dialysis-requiring acute kidney injury (D-AKI) is a major complication of cardiovascular surgery that results in worse prognosis. However, the incidence and impacts of D-AKI in different types of cardiac surgeries have not been fully investigated. Methods and Results Patients admitted for cardiovascular surgery between July 1, 2004, and December 31, 2013, were identified from the National Health Insurance Research Database of Taiwan. The patients were grouped into D-AKI (n=3089) and non-D-AKI (n=42 151) groups. The outcome was all-cause mortality and major adverse kidney event. The long-term outcomes were worse in the D-AKI group than the non-D-AKI group (hazard ratio [HR], 3.89; 95% CI, 3.79-3.99 for major adverse kidney event; HR, 2.89; 95% CI, 2.81-2.98 for all-cause mortality). Patients who underwent aortic surgery had higher risk for D-AKI than other types of surgeries, but they were also more likely to recover. The long-term dialysis rate for the patients who recovered from D-AKI was also lowest in those who underwent aortic surgery. Among all types of cardiac surgeries with D-AKI, patients who had heart valve surgery exhibited the greatest risks of all-cause mortality (HR, 6.04; 95% CI, 5.78-6.32). Conclusions Compared with other heart surgeries, aortic surgery resulted in a higher incidence of D-AKI but better renal recovery, better short-term outcome, and lower incidences of long-term dialysis.
| S-EPMC8200754 | biostudies-literature
Project description:Acute kidney injury (AKI) is common and portends mortality in several neonatal cohorts. Fluid overload is independently associated with poor outcomes in children and adults but has not been extensively studied in neonates.Between February 2010 and May 2011, we followed 58 neonates who met the following criteria: birth weight >2,000 g, gestational age ≥ 34 weeks, 5-min Apgar ≤ 7, and parental consent. Serum creatinine (SCr) was measured daily for first 4 days of life. AKI was defined as a rise in SCr of > 0.3 mg/dl or persistent SCr above 1.5 mg/dl.AKI was present in 9/58 (15.6 %) neonates and was associated with higher birth weight, being male, lower 5-min Apgar scores, lower cord pH, delivery room intubation, and absence of maternal pre-eclampsia. Percent weight accumulation at day 3 of life was higher in those with AKI [median=8.2, interquartile range (IQR) =4.4-21.6)] than without AKI (median= -4 (IQR= -6.5 to 0.0) (p<0.001). Infants with AKI had lower survival rates than those without AKI [7/9 (72 %) vs. 49/49 (100 %) (p<0.02)].AKI incidence in this neonatal population is similar to other neonatal cohorts. Near-term/term infants with AKI have a higher mortality rate and a net positive fluid balance over the first few days of life.
| S-EPMC5545796 | biostudies-other
Project description: Not available
| S-EPMC11336529 | biostudies-literature
Project description:ObjectivePrompt assessment of perioperative complications is critical for the comprehensive care of surgical patients. Acute kidney injury requiring dialysis (AKI-D) is associated with high mortality, yet little is known about how long-term outcomes of patients have evolved. The association of AKI-D with postsurgical outcomes has not been well studied.MethodsWe investigated patients from the National Health Insurance Research Database and validated by the multicenter Clinical Trial Consortium for Renal Diseases cohort. All patients with AKI-D 18 years or older undergoing four major surgeries (cardiothoracic, esophagus, intestine, and liver) were retrospectively investigated (N=106,573). Patient demographics, surgery type, comorbidities before admission, and postsurgical outcomes, including the in-hospital, 30-day, and long-term mortality together with dialysis dependence were collected.ResultsAKI-D is the top risk factor for 30-day and long-term mortality after major surgery. Of 1,664 individuals with AKI-D and 6,656 matched controls, AKI-D during the hospital stay was associated with in-hospital (adjusted hazard ratio [aHR]=3.04, 95% CI 2.79-3.31), 30-day (aHR=3.65, 95% CI 3.37-3.94), and long-term (aHR=3.22, 95% CI 3.01-3.44) mortality. Patients undergoing cardiothoracic surgery (CTS) showed less in-hospital (aHR=0.85, 95% CI 0.75-0.97), 30-day (aHR=0.79, 95% CI 0.70-0.89), and long-term (aHR=0.80, 95% CI 0.72-0.90) mortality compared with non-CTS patients with AKI-D. CTS patients had a high risk of 30-day dialysis dependence (subhazard ratio [sHR]=1.67, 95% CI 1.18-2.38), but the risk of long-term dialysis dependence was similar (sHR=1.38, 95% CI 0.96-2.00) after AKI-D by taking mortality as a competing risk. Non-CTS patients had more comorbidities of sepsis, azotemia, hypoalbuminemia, and metabolic acidosis compared with CTS patients.ConclusionAKI exhibits paramount effects on postsurgical outcomes that extend well beyond discharge from the hospital. The goal of the perioperative assessment should include the reassurance of enhancing renal function recovery among different surgeries, and optimized follow-up is warranted in attenuating the complications after postsurgical AKI has occurred.
| S-EPMC6208534 | biostudies-literature
Project description:Cannabinoids and their endogenous and synthetic analogs impact blood pressure and contribute to the incidence of hypertension. It was previously reported that the endocannabinoid system plays an important role in developing hypertension; however, it was also shown that cannabinoids elicit profound hypotension associated with hemorrhagic, cardiogenic, and endotoxic shock. This study aimed to test acute and chronic effects of an endogenous ligand of cannabinoid receptor anandamide (AEA) on blood pressure and kidney injury in vivo in conscious Dahl salt-sensitive (SS) rats. We demonstrated that acute i.v. bolus administration of a low or a high doses (0.05 or 3 mg/kg) of AEA did not affect blood pressure for 2 h after the injection in Dahl SS rats fed a normal salt diet (0.4% NaCl). Neither low nor high doses of AEA had any beneficial effects on blood pressure or kidney function. Furthermore, hypertensive rats fed a HS diet (8% NaCl) and chronically treated with 3 mg/kg of AEA exhibited a significant increase in blood pressure accompanied by increased renal interstitial fibrosis and glomerular damage at the late stage of hypertension. Western blot analyses revealed increased expression of Smad3 protein levels in the kidney cortex in response to chronic treatment with a high AEA dose. Therefore, TGF-β1/Smad3 signaling pathway may play a crucial role in kidney injury in SS hypertension during chronic treatment with AEA. Collectively, these data indicate that prolonged stimulation of cannabinoid receptors may result in aggravation of hypertension and kidney damage.
| S-EPMC9005691 | biostudies-literature