Dataset Information

Effect of alkaline phosphatase on sepsis-associated acute kidney injury patients: A systematic review and meta-analysis.

ABSTRACT:

Background

This systematic review and meta-analysis were performed to evaluate kidney function in patients with sepsis-associated acute kidney injury (SA-AKI) on alkaline phosphatase (AP) therapy.

Methods

PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched electronically from inception until May 4, 2019 and randomized controlled studies assessing AP treatment in patients with SA-AKI were included. Pool analyses with fixed effects or random effects models calculated pooled mean, standard deviation, and odds ratio (OR) with 95% confidence interval (CI).

Results

Four randomized controlled trials involving AP therapy for 392 patients with SA-AKI were included. AP had a positive effect on endogenous creatinine clearance (ECC) in patients with SA-AKI at day 14 (random effects: mean difference?=?10.56, 95% CI?=?2.27-18.84, P?=?.01) and day 28 (random effects: mean difference?=?14.30, 95% CI?=?6.27-22.33, P?=?.0005). All-cause mortality at day 28 (fixed effects: OR?=?0.62, 95% CI?=?0.40-0.97, P?=?.04) and day 90 (fixed effects: OR?=?0.61, 95% CI?=?0.39-0.96, P?=?.03) improved. Plasma creatinine level (fixed effects: mean difference?=?-76.83, 95% CI?=?-146.92 to -6.74, P?=?.03) and biomarkers level (random effects: mean difference?=?-6.57, 95% CI?=?-10.74 to -2.40, P?ConclusionIn patients with SA-AKI, AP showed a relatively late protective effect by improving ECC at days 7, 14, and 28. ECC level improved when patients received AP dose of 0.212?mg/kg. Mortality improved at days 28 and 90, respectively, when patients received AP dose of 1.6?mg/kg. Levels of overall AKI biomarkers were improved in short term.

SUBMITTER: Tang W

PROVIDER: S-EPMC7004577 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Effect of alkaline phosphatase on sepsis-associated acute kidney injury patients: A systematic review and meta-analysis.

Tang Wenting W Huang Junlin J Huang Xiaowen X Han Xiao X Tang Wenyi W Ke Guibao G Xu Qingqing Q

Medicine 20200101 4

<h4>Background</h4>This systematic review and meta-analysis were performed to evaluate kidney function in patients with sepsis-associated acute kidney injury (SA-AKI) on alkaline phosphatase (AP) therapy.<h4>Methods</h4>PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched electronically from inception until May 4, 2019 and randomized controlled studies assessing AP treatment in patients with SA-AKI were included. Pool analyses with fixed effects or random effects ...[more]

PMID: 31977869

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Project description:IntroductionTo evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed.MethodsThirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety.ResultsThere was a significant (P=0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50±27 to 108±73 mL/minute (mean±SEM) for the AP group; and from 40±37 to 65±30 mL/minute for placebo; P=0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial.ConclusionsThe improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI.Trial registrationwww.clinicaltrials.gov: NCT00511186.

Project description:Importance:Sepsis-associated acute kidney injury (AKI) adversely affects long-term kidney outcomes and survival. Administration of the detoxifying enzyme alkaline phosphatase may improve kidney function and survival. Objective:To determine the optimal therapeutic dose, effect on kidney function, and adverse effects of a human recombinant alkaline phosphatase in patients who are critically ill with sepsis-associated AKI. Design, Setting, and Participants:The STOP-AKI trial was an international (53 recruiting sites), randomized, double-blind, placebo-controlled, dose-finding, adaptive phase 2a/2b study in 301 adult patients admitted to the intensive care unit with a diagnosis of sepsis and AKI. Patients were enrolled between December 2014 and May 2017, and follow-up was conducted for 90 days. The final date of follow-up was August 14, 2017. Interventions:In the intention-to-treat analysis, in part 1 of the trial, patients were randomized to receive recombinant alkaline phosphatase in a dosage of 0.4 mg/kg (n?=?31), 0.8 mg/kg (n?=?32), or 1.6 mg/kg (n?=?29) or placebo (n?=?30), once daily for 3 days, to establish the optimal dose. The optimal dose was identified as 1.6 mg/kg based on modeling approaches and adverse events. In part 2, 1.6 mg/kg (n?=?82) was compared with placebo (n?=?86). Main Outcomes and Measures:The primary end point was the time-corrected area under the curve of the endogenous creatinine clearance for days 1 through 7, divided by 7 to provide a mean daily creatinine clearance (AUC1-7 ECC). Incidence of fatal and nonfatal (serious) adverse events ([S]AEs) was also determined. Results:Overall, 301 patients were enrolled (men, 70.7%; median age, 67 years [interquartile range {IQR}, 59-73]). From day 1 to day 7, median ECC increased from 26.0 mL/min (IQR, 8.8 to 59.5) to 65.4 mL/min (IQR, 26.7 to 115.4) in the recombinant alkaline phosphatase 1.6-mg/kg group vs from 35.9 mL/min (IQR, 12.2 to 82.9) to 61.9 mL/min (IQR, 22.7 to 115.2) in the placebo group (absolute difference, 9.5 mL/min [95% CI, -23.9 to 25.5]; P?=?.47). Fatal adverse events occurred in 26.3% of patients in the 0.4-mg/kg recombinant alkaline phosphatase group; 17.1% in the 0.8-mg/kg group, 17.4% in the 1.6-mg/kg group, and 29.5% in the placebo group. Rates of nonfatal SAEs were 21.0% for the 0.4-mg/kg recombinant alkaline phosphatase group, 14.3% for the 0.8-mg/kg group, 25.7% for the 1.6-mg/kg group, and 20.5% for the placebo group. Conclusions and Relevance:Among patients who were critically ill with sepsis-associated acute kidney injury, human recombinant alkaline phosphatase compared with placebo did not significantly improve short-term kidney function. Further research is necessary to assess other clinical outcomes. Trial Registration:ClinicalTrials.gov Identifier: NCT02182440.

Project description:BackgroundDue to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute kidney injury (AKI). However, the opinions on relevant predictive risk factors remain inconclusive. This study aimed to provide a systematic review and meta-analysis to determine the predisposing factors for sepsis-associated AKI.MethodA systematic literature search was performed in the Medline, Embase, Cochrane Library, PubMed, and Web of Science, databases, with an end-date of 25th May 2019. Valid data were retrieved in compliance with specific inclusion and exclusion criteria.ResultForty-seven observational studies were included for analysis, achieving a cumulative patient number of 55,911. The highest incidence of AKI was caused by septic shock. Thirty-one potential risk factors were included in the meta-analysis. Analysis showed that 20 factors were statistically significant. The odds ratio (OR) and 95% confidence interval (CI), as well as the prevalence of the most frequently-seen predisposing factors for sepsis-associated AKI, were as follows: septic shock [2.88 (2.36-3.52), 60.47%], hypertension [1.43 (1.20-1.70), 38.39%], diabetes mellitus [1.59 (1.47-1.71), 27.57%], abdominal infection [1.44 (1.32-1.58), 30.87%], the administration of vasopressors [2.95 (1.67-5.22), 64.61%], the administration of vasoactive drugs [3.85 (1.89-7.87), 63.22%], mechanical ventilation [1.64 (1.24-2.16), 68.00%], positive results from blood culture [1.60 (1.35-1.89), 41.19%], and a history of smoking [1.60 (1.09-2.36), 43.09%]. Other risk factors included cardiovascular diseases, coronary artery diseases, liver diseases, unknown infections, the administration of diuretics and ACEI/ARB, the infection caused by gram-negative bacteria, and organ transplantation.ConclusionRisk factors of S-AKI arise from a wide range of sources, making it difficult to predict and prevent this condition. Comorbidities, and certain drugs, are the main risk factors for S-AKI. Our review can provide guidance on the application of interventions to reduce the risks associated with sepsis-associated acute kidney injury and can also be used to tailor patient-specific treatment plans and management strategies in clinical practice.

Project description:BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early biomarker for prediction of acute kidney injury (AKI). However, the utility of NGAL to predict the occurrence of AKI in septic patients remains controversial. We performed a systematic review and meta-analysis to evaluate the evidence on diagnosis of sepsis AKI and the prediction of other clinical outcomes.MethodThe MEDLINE, EMBASE, Cochrane Library, Wanfang, and CNKI databases were systematically searched up to August 19, 2015. Quality assessment was applied by using the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tool. The diagnostic performance of NGAL for the prediction of AKI in sepsis was evaluated using pooled estimates of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio (DOR), as well as summary receiver operating characteristic curves (SROC).ResultsFifteen studies with a total of 1,478 patients were included in the meta-analysis. For plasma NGAL, the pooled sensitivity and specificity with corresponding 95% confidence intervals (CI) were 0.83 (95% CI: 0.77 - 0.88) and 0.57 (95% CI: 0.54 - 0.61), respectively. The pooled positive likelihood ratio (PLR) was 3.10 (95% CI: 1.57 - 6.11) and the pooled negative likelihood ratio (NLR) was 0.24 (95% CI: 0.13 - 0.43). The pooled DOR was 14.72 (95% CI: 6.55 - 33.10) using a random effects model. The area under the curve (AUC) for SROC to summarize diagnostic accuracy was 0.86. For urine NGAL, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC values were 0.80 (95% CI: 0.77 - 0.83), 0.80 (95% CI: 0.77 - 0.83), 4.42 (95% CI: 2.84 - 6.89), 0.21 (95% CI: 0.13 - 0.35), 24.20 (95% CI: 9.92 - 59.05) and 0.90, respectively. Significant heterogeneity was explored as a potential source. There was no notable publication bias observed across the eligible studies. NGAL for prediction of renal replacement therapy (RRT) and mortality associated with AKI in septic patients were also evaluated.ConclusionTo a certain extent, NGAL is not only an effective predictive factor for AKI in the process of sepsis, but also shows potential predictive value for RRT and mortality. However, future trials are needed to clarify this controversial issue.

Project description:Lung transplantation has been increasingly performed worldwide and is considered an effective therapy for patients with various causes of end-stage lung diseases. We performed a systematic review to assess the incidence and impact of acute kidney injury (AKI) and severe AKI requiring renal replacement therapy (RRT) in patients after lung transplantation. A literature search was conducted utilizing Ovid MEDLINE, EMBASE, and Cochrane Database from inception through June 2019. We included studies that evaluated the incidence of AKI, severe AKI requiring RRT, and mortality risk of AKI among patients after lung transplantation. Pooled incidence and odds ratios (ORs) with 95% confidence interval (CI) were obtained using random-effects meta-analysis. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019134095). A total of 26 cohort studies with a total of 40,592 patients after lung transplantation were enrolled. Overall, the pooled estimated incidence rates of AKI (by standard AKI definitions) and severe AKI requiring RRT following lung transplantation were 52.5% (95% CI: 45.8-59.1%) and 9.3% (95% CI: 7.6-11.4%). Meta-regression analysis demonstrated that the year of study did not significantly affect the incidence of AKI (p = 0.22) and severe AKI requiring RRT (p = 0.68). The pooled ORs of in-hospital mortality in patients after lung transplantation with AKI and severe AKI requiring RRT were 2.75 (95% CI, 1.18-6.41) and 10.89 (95% CI, 5.03-23.58). At five years, the pooled ORs of mortality among patients after lung transplantation with AKI and severe AKI requiring RRT were 1.47 (95% CI, 1.11-1.94) and 4.79 (95% CI, 3.58-6.40), respectively. The overall estimated incidence rates of AKI and severe AKI requiring RRT in patients after lung transplantation are 52.5% and 9.3%, respectively. Despite advances in therapy, the incidence of AKI in patients after lung transplantation does not seem to have decreased. In addition, AKI after lung transplantation is significantly associated with reduced short-term and long-term survival.

Dataset Information

Effect of alkaline phosphatase on sepsis-associated acute kidney injury patients: A systematic review and meta-analysis.

Background

Methods

Results

Publications

Effect of alkaline phosphatase on sepsis-associated acute kidney injury patients: A systematic review and meta-analysis.

Similar Datasets

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