Reliability of neutrophil gelatinase-associated lipocalin in detecting acute tubular necrosis in decompensated cirrhosis:Systematic review and meta-analysis

BACKGROUND Acute kidney injury(AKI)in cirrhosis is common.The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine.However,urine biomarkers could also be used to assess the type of AKI and the severity of the disease.We performed a systematic review with metaanalysis to evaluate the association with urine neutrophil gelatinase-associated lipocalin(NGAL)marker in identifying acute tubular necrosis(ATN)in patients with cirrhosis.AIM To assess the reliability of urine NGAL in the detection of ATN in patients with cirrhosis.METHODS We systematically searched MEDLINE and PubMed using keywords including“urine biomarkers”,“NGAL”,“kidney dysfunction”,and“cirrhosis”to identify relevant studies.Data was screened and extracted.Included studies assessed hospitalized cirrhosis patients with AKI using the urine NGAL biomarker.We synthesized the data using diagnostic odds ratio(DOR),comparative and descriptive analyses,and Cochran Mantel-Haenszel(CMH)statistics to evaluate heterogeneity.RESULTS Three thousand seven hundred and one patients with cirrhosis were analyzed from a total of 21 cohort studies.The DOR of 14 of those studies[pooled DOR:22.150,(95%CI:17.58-27.89),P<0.0001]demonstrated a significant association between urine NGAL levels and its identification of ATN.Following stratification by cirrhosis status,heterogeneity was analyzed and showed a significant non-zero correlation between NGAL and AKI(CMH statistic=702.19,P<0.0001).CONCLUSION In patients with cirrhosis,the use of urine NGAL is a reliable biomarker for detecting ATN and identifying the etiology of AKI.

Angiotensin Ⅱ receptor blockers and gastrointestinal adverse events of resembling sprue-like enteropathy:a systematic review

Background:Olmesartan,an angiotensin Ⅱ receptor blocker(ARB),is associated with gastrointestinal symptoms resembling sprue-like enteropathy.Some have proposed that enteropathy may be a class effect rather than olmesartan-specific.We performed a systematic review to identify literature of sprue-like enteropathy for all ARBs.Methods:Case reports,case series and comparative studies of ARBs were searched on PubMed and Embase databases through 21 November 2018 and then assessed.Results:A total of 82 case reports and case series as well as 5 comparative studies,including 248 cases,were selected and analysed.The ARBs listed in the case reports were olmesartan(233 users;94.0%),telmisartan(5 users;2.0%),irbesartan(4 users;1.6%),valsartan(3 users;1.2%),losartan(2 users;0.8%)and eprosartan(1 user;0.4%).The periods between ARB initiation and onset of symptoms ranged from 2 weeks to 13 years.Histologic results were reported in 218 cases,in which 201 cases(92.2%)were villous atrophy and 131 cases(60.1%)were intraepithelial lymphocytosis.Human leucocyte antigen(HLA)testing was performed in 147 patients,among whom 105(71.4%)had HLA-DQ2 or HLA-DQ8 haplotypes.Celiacassociated antibodies were tested in 169 patients,among whom 167(98.8%)showed negative results.Gluten exclusion from the diet failed to relieve symptoms of enteropathy in 127(97.7%)of 130 patients with information.Complete remission of symptoms after discontinuation of ARB was reported in 233(97.4%)of the 239 patients with information.Seven cases(2.8%)reported recurrence of symptoms after restarting olmesartan;rechallenge was not reported for the non-olmesartan ARBs.The retrospective studies conducted worldwide had inconsistent study designs(e.g.differences in periods of study and case definition)and findings.Conclusions:Although enteropathy is rare,clinicians should remain vigilant of this potential adverse event even years after medication initiation.