Tolvaptan in the treatment of acute hyponatremia associated with acute kidney injury.
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ABSTRACT:
SUBMITTER: Gopinath S
PROVIDER: S-EPMC3914017 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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Tolvaptan in the treatment of acute hyponatremia associated with acute kidney injury.
Gopinath Shilpa S Janga Kalyana C KC Greenberg Sheldon S Sharma Shree K SK
Case reports in nephrology 20131120
Hyponatremia defined as a plasma sodium concentration of less than 135 mmol/L is a very common disorder, occurring in hospitalized patients. Hyponatremia often results from an increase in circulating arginine vasopressin (AVP) levels and/or increased renal sensitivity to AVP, combined with an increased intake of free water. Hyponatremia is subdivided into three groups, depending on clinical history and volume status: hypovolemic, euvolemic, and hypervolemic. Acute symptomatic hyponatremia is usu ...[more]
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Project description:BACKGROUND:Although tolvaptan treatment improves hyponatremia, only few studies have investigated whether tolvaptan actually benefits the survival of cirrhotic patients. This study evaluated the impact of tolvaptan on six-month survival of decompensated cirrhotic patients with and without hyponatremia. METHODS:Two hundred forty-nine decompensated cirrhotic patients with or without hyponatremia were enrolled in a multicenter cohort study. Patients were divided into two groups according to receiving either tolvaptan or placebo treatment for 7-day. Subsequently, the patients were followed up for 6 months. RESULTS:Two hundred thirty patients, including 98 with hyponatremia (tolvaptan vs. placebo: 69 vs. 29) finished the study. Tolvaptan did not alter serum sodium levels and survival outcome of decompensated cirrhotic patients without hyponatremia. However, tolvaptan treatment remarkably improved serum sodium levels and six-month survival in patients with hyponatremia. Following tolvaptan treatment, serum sodium levels were restored to normal in 63.8% of patients, whereas in patients receiving placebo, only 36.2% showed the same effect (P?<?0.05). Compared to a six-month survival rate of 68.97% in patients receiving placebo, the survival rate in tolvapatan-treated patients was 89.94% (P?<?0.05). Furthermore, six-month survival rate in the tolvaptan-treated hyponatremia patients with resolved serum sodium was 81.32%, whereas the survival in those with unresolved serum sodium was only 24% (P?<?0.05). CONCLUSIONS:Tolvaptan improves short term survival in most decompensated cirrhotic hyponatremia patients with resolved serum sodium. TRIALS REGISTRATION:Clinical trial one: ClinicalTrials.gov ID: NCT00664014 , Registered on April 14, 2008. Clinical trial two: ClinicalTrials.gov ID: NCT01349335 , Registered on March 5, 2010. Clinical trial three: ClinicalTrials.gov ID: NCT01349348 , Registered on May 4, 2011.
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Project description:Context:The relevance of hyponatremia has been acknowledged by guidelines from the United States (2013) and Europe (2014). However, treatment recommendations differ due to limited evidence. Objective:In hyponatremia following pituitary surgery-caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion-we compared fluid restriction with the pharmacological increase of water excretion by blocking the vasopressin 2 receptors with tolvaptan at a low and a moderate dose. Design:Prospective observational study. Setting:Neurosurgical Department of a University hospital with more than 200 surgical pituitary procedures per year. Patients:Patients undergoing pituitary surgery and developing serum sodium below 136 mmol/L. The diagnosis of SIADH was established by euvolemia (daily measurement of body weight and fluid balance), inappropriately concentrated urine (specific gravity), and exclusion of adrenocorticotropic and thyroid-stimulating hormone deficiency. Intervention:Patients were treated with fluid restriction (n?=?40) or tolvaptan at 3.75 (n?=?38) or 7.5 mg (n?=?48). Main Outcome Measures:Treatment efficacy was assessed by the duration of hyponatremia, sodium nadir, and length of hospitalization. Safety was established by a sodium increment below 10 mmol/L per day and exclusion of side effects. Results:Treatment with 7.5 mg of tolvaptan resulted in a significant attenuation of hyponatremia and in a significant overcorrection of serum sodium in 30% of patients. The duration of hospitalization did not differ between treatment groups. Conclusions:Tolvaptan at a moderate dose is more effective than fluid restriction in the treatment of SIADH. Overcorrection of serum sodium may be a side effect of tolvaptan even at low doses.
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Project description:Background and aimAcute kidney injury (AKI) is a life-threatening complication of liver cirrhosis. Here, we evaluated the risk factors and characteristics of AKI in cirrhosis.Patients/methodsThis was a single-center retrospective study. A total of 199 Japanese patients with decompensated liver cirrhosis (104 men, median age 61 years) were enrolled and received tolvaptan orally. Survival rates and new onset of AKI were monitored, and risk factors were evaluated.ResultsForty-six patients (23.1%) suffered an AKI complication and exhibited significantly poorer survival (P < 0.01). The rates of hepatic encephalopathy (P < 0.01) and chronic kidney disease (CKD; P = 0.02) were significantly increased in patients with AKI. The rate of proton pump inhibitor (PPI)/H2 blocker treatment (P = 0.04) was significantly lower, whereas that of ascites drainage was significantly higher in the AKI cases (P < 0.01). The AKI risk was significantly increased in patients with hepatic encephalopathy (HR 4.18, 95% CI 1.618-10.771). In contrast, the incidence of AKI was significantly lower in patients with a higher serum albumin level (HR 0.36, 95% CI 0.142-0.914, P = 0.03). Treatment with PPI/H2 blockers (HR 0.30, 95% CI 0.126-0.711, P < 0.01) or kanamycin/rifaximin (HR 0.26, 95% CI 0.075-0.929, P = 0.04) was significantly associated with a reduced risk of AKI development.ConclusionsAKI incidence was increased in patients with decreased liver function and was associated with poor survival. PPI/H2 blocker or kanamycin/rifaximin treatment may reduce the risk of AKI.
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Project description:BACKGROUND:Acute kidney injury (AKI) is the most frequent extra-pulmonary organ failure in acute respiratory distress syndrome (ARDS). The objective of this study was to assess the factors associated with the development and severity of AKI in patients with ARDS. METHODS:This is a retrospective cohort study of ARDS patients without acute or chronic kidney disease prior to the onset of ARDS over a 7-year period (2010-2017). AKI and severity of AKI were defined according to the Kidney Disease Improving Global Outcomes 2012 guidelines. RESULTS:Of the 634 ARDS patients, 357 patients met study criteria. A total of 244 (68.3%) patients developed AKI after ARDS onset: 60 (24.6%) had stage I AKI, 66 (27%) had stage II AKI, and 118 (48.4%) had stage III AKI. The median time of AKI onset for stage I AKI was 2 days (interquartile range, 1.5-5.5) while stage II and III AKI was 4 days. On multivariable analysis, factors associated with development of AKI were age [subdistribution hazard ratio (SHR) 1.01, 95% confidence interval (CI) 1.00-1.02], SOFA score (SHR 1.16, 95%CI 1.12-1.21), a history of diabetes mellitus (DM) (SHR 1.42, 95%CI 1.07-1.89), and arterial pH on day 1 of ARDS (SHR per 0.1 units decrease was 1.18, 95%CI 1.05-1.32). In severity of AKI, stage I AKI was associated with age (SHR 1.03, 95%CI 1.01-1.05) and serum bicarbonate on day 1 of ARDS (SHR 1.07, 95%CI 1.02-1.13). Stage II AKI was associated with age (SHR 1.03, 95%CI 1.01-1.05), serum bicarbonate on day 1 (SHR 1.12, 95%CI 1.06-1.18), SOFA score (SHR 1.19, 95%CI 1.10-1.30), history of heart failure (SHR 3.71, 95%CI 1.63-8.46), and peak airway pressure (SHR 1.04, 95%CI 1.00-1.07). Stage III AKI was associated with a higher BMI (SHR 1.02, 95%CI 1.00-1.03), a history of DM (SHR 1.79, 95%CI 1.18-2.72), SOFA score (SHR 1.29, 95%CI 1.22-1.36), and arterial pH on day 1 (SHR per 0.1 units decrease was 1.25, 95%CI 1.05-1.49). CONCLUSIONS:Age, a higher severity of illness, a history of diabetes, and acidosis were associated with development of AKI in ARDS patients. Severity of AKI was further associated with BMI, history of heart failure, and peak airway pressure.
| S-EPMC6603088 | biostudies-other
Project description:It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality.Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative vs. liberal fluid management and of management guided by a central venous vs. pulmonary artery catheter.Acute Respiratory Distress Syndrome Network hospitals.One thousand patients.None.The incidence of acute kidney injury, defined as an absolute rise in creatinine of ?0.3 mg/dL or a relative change of >50% over 48 hrs, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of acute kidney injury before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57% vs. 51%, p = .04). After adjustment for fluid balance, the incidence of acute kidney injury was greater in those managed with the liberal fluid protocol (66% vs. 58%, p = .007). Patients who met acute kidney injury criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet acute kidney injury criteria both before and after adjustment for fluid balance (31% vs. 12%, p < .001) and those who had acute kidney injury before but not after adjustment for fluid balance (31% vs. 11%, p = .005). The mortality of those patients meeting acute kidney injury criteria after but not before adjustment for fluid balance was similar to patients with acute kidney injury both before and after adjustment for fluid balance (31% vs. 38%, p = .18).Fluid management influences serum creatinine and therefore the diagnosis of acute kidney injury using creatinine-based definitions. Patients with "unrecognized" acute kidney injury that is identified after adjusting for positive fluid balance have higher mortality rates, and patients who have acute kidney injury before but not after adjusting for fluid balance have lower mortality rates. Future studies of acute kidney injury should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis.
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Project description:INTRODUCTION:Vancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS:A 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI. RESULTS:A total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6-8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05). CONCLUSIONS:Moderate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.
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Project description:Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.
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Project description:Acute kidney injury (AKI) is common among hospitalized patients with coronavirus disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. An improved knowledge of the pathology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who develop AKI during COVID-19. In this review, we summarize the published cases and case series of various kidney pathologies seen with COVID-19. Both live kidney biopsies and autopsy series suggest acute tubular injury as the most commonly encountered pathology. Collapsing glomerulopathy and thrombotic microangiopathy are other encountered pathologies noted in both live and autopsy tissues. Other rare findings such as anti-neutrophil cytoplasmic antibody vasculitis, anti-glomerular basement membrane disease and podocytopathies have been reported. Although direct viral infection of the kidney is possible, it is certainly not a common or even widespread finding reported at the time of this writing (November 2020).
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