title: Are Urinary Tubular Injury Markers Useful in Chronic Kidney Disease? A Systematic Review and Meta Analysis.
abstract: BACKGROUND
  Adverse outcome of chronic kidney disease, such as end stage renal disease, is a significant burden on personal health and healthcare costs. Urinary tubular injury markers, such as NGAL, KIM-1 and NAG, could provide useful prognostic value for the early identification of high-risk patients. However, discrepancies between recent large prospective studies have resulted in controversy regarding the potential clinical value of these markers. Therefore, we conducted the first meta-analysis to provide a more persuasive argument to this debate.
  
  
  METHODS
  In the current meta-analysis, based on ten prospective studies involving 29366 participants, we evaluated the role of urinary tubular injury markers (NGAL, KIM-1 and NAG) in predicting clinical outcomes including CKD stage 3, end stage renal disease and mortality. The prognostic values of these biomarkers were estimated using relative risks and 95% confidence interval in adjusted models. All risk estimates were normalized to those of 1 standard deviation increase in log-scale concentrations to minimize heterogeneity. Fixed-effects models were adopted to combine risk estimates. The quality of the research and between-study heterogeneity were evaluated. The level of research evidence was identified according to the GRADE profiler.
  
  
  RESULTS
  uNGAL was identified as an independent risk predictor of ESRD (pooled adjusted relative risk: 1.40[1.21 to 1.61], p<0.001) and of overall mortality (pooled adjusted relative risk: 1.10[1.03 to 1.18], p = 0.001) in patients with chronic kidney disease. A borderline significance of uKIM-1 in predicting CKD stage 3 independently in the community-based population was observed (pooled adjusted relative risk: 1.13[1.00 to 1.27], p = 0.057). Only the prognostic value of uNGAL for ESRD was supported by a grade B level of evidence.
  
  
  CONCLUSIONS
  The concentration of uNGAL can be used in practice as an independent predictor of end stage renal disease among patients with chronic kidney disease, but it may be not useful in predicting disease progression to CKD stage 3 among community-based population.
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Le-Ting
authors.initials: LT
authors.lastname: Zhou
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Lv
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Pan
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Cao
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Ni
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D015415:Biomarkers / Q000652:urine*; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000503:physiopathology / Q000652:urine*; D007684:Kidney Tubules / Q000293:injuries / Q000473:pathology; D000071068:Lipocalin-2 / Q000652:urine*; D008297:Male; D009363:Neoplasm Proteins / Q000652:urine*; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000401:mortality / Q000503:physiopathology / Q000652:urine*
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; C117339:NBAS protein, human; D009363:Neoplasm Proteins