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Novel Therapies for Acute Kidney Injury.

ABSTRACT: Acute kidney injury (AKI) is a common disease with a complex pathophysiology. The old paradigm of identifying renal injury based on location-prerenal, intrarenal, and postrenal-is now being supplanted with a new paradigm based on observable kidney injury patterns. The pathophysiology of AKI on a molecular and microanatomical level includes inflammation, immune dysregulation, oxidative injury, and impaired microcirculation. Treatment has traditionally been supportive, including the avoidance of nephrotoxins, judicious volume and blood pressure management, hemodynamic monitoring, and renal replacement therapy. Fluid overload and chloride-rich fluids are now implicated in the development of AKI, and resuscitation with a balanced, buffered solution at a conservative rate will mitigate risk. Novel therapies, which address specific observable kidney injury patterns include direct oxygen-free radical scavengers such as ?-lipoic acid, curcumin, sodium-2-mercaptoethane sulphonate, propofol, and selenium. In addition, angiotensin II and adenosine receptor antagonists hope to ameliorate kidney injury via manipulation of renal hemodynamics and tubulo-glomerular feedback. Alkaline phosphatase, sphingosine 1 phosphate analogues, and dipeptidylpeptidase-4 inhibitors counteract kidney injury via manipulation of inflammatory pathways. Finally, genetic modifiers such as 5INP may mitigate AKI via transcriptive processes.

SUBMITTER: Chen H

PROVIDER: S-EPMC5733745 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Novel Therapies for Acute Kidney Injury.

Chen Huaizhen H Busse Laurence William LW

Kidney international reports 20170628 5

Acute kidney injury (AKI) is a common disease with a complex pathophysiology. The old paradigm of identifying renal injury based on location-prerenal, intrarenal, and postrenal-is now being supplanted with a new paradigm based on observable kidney injury patterns. The pathophysiology of AKI on a molecular and microanatomical level includes inflammation, immune dysregulation, oxidative injury, and impaired microcirculation. Treatment has traditionally been supportive, including the avoidance of n ...[more]

PMID: 29270486

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Project description:The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers.Cross-sectional prospective.Hospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36).We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C.Urine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C.We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs).Neither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96).No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors.All candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation prior to freezing. For optimal fidelity, urine for IL-18 measurement should not be stored at 25°C before long-term storage or analysis.

Project description:Background: Dialysis-dependent acute kidney injury (AKI) can be treated using continuous (CRRT) or intermittent renal replacement therapies (IRRT). Although some studies suggest that CRRT may have advantages over IRRT, study findings are inconsistent. This study assessed differences between CRRT and IRRT regarding important clinical outcomes (such as mortality and renal recovery) and cost-effectiveness. Additionally, ethical aspects that are linked to renal replacement therapies in the intensive care setting are considered. Methods: Systematic searches in MEDLINE, EMBASE, and Cochrane Library including RCTs, observational studies, and cost-effectiveness studies were performed. Results were pooled using a random effects-model. Results: Forty-nine studies were included. Findings show a higher rate of renal recovery among survivors who initially received CRRT as compared with IRRT. This advantage applies to the analysis of all studies with different observation periods (Relative Risk (RR) 1.10; 95% Confidence Interval (CI) [1.05, 1.16]) and to a selection of studies with observation periods of 90 days (RR 1.07; 95% CI [1.04, 1.09]). Regarding observation periods beyond there are no differences when only two identified studies were analyzed. Patients initially receiving CRRT have higher mortality as compared to IRRT (RR 1.17; 95% CI [1.06, 1.28]). This difference is attributable to observational studies and may have been caused by allocation bias since seriously ill patients more often initially receive CRRT instead of IRRT. CRRT do not significantly differ from IRRT with respect to change of mean arterial pressure, hypotensive episodes, hemodynamic instability, and length of stay. Data on cost-effectiveness is inconsistent. Recent analyzes indicate that initial CRRT is cost-effective compared to initial IRRT due to a reduction of the rate of long-term dialysis dependence. As regards a short time horizon, this cost benefit has not been shown. Conclusion: Findings of the conducted assessment show that initial CRRT is associated with higher rates of renal recovery. Potential long-term effects on clinical outcomes for more than three months could not be analyzed and should be investigated in further studies. Economical analyzes indicate that initial CRRT is cost-effective when costs of long-term dialysis dependence are considered. However, transferability of the economic analyzes to the German health care system is limited and the conduction of economical analyzes using national cost data should be considered.

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Novel Therapies for Acute Kidney Injury.

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Novel Therapies for Acute Kidney Injury.

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