title: Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression.
abstract: Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers.
authors.affiliation: University of California, San Francisco, San Francisco, California, USA; Kaiser Permanente Northern California, Oakland, California, USA. Electronic address: hsuchi@medicine.ucsf.edu.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Venkata
authors.initials: V
authors.lastname: Sabbisetti
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Mifflin
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Diamantidis
authors.affiliation: Tulane University, New Orleans, Louisiana, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: University of Illinois, Chicago, Illinois, USA.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Lora
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Miller
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
authors.affiliation: University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Akinlolu O
authors.initials: AO
authors.lastname: Ojo
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Mahboob
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Schelling
authors.affiliation: Yale University, New Haven, Connecticut, USA.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Wilson
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.affiliation: Boston University, Boston, Massachusetts, USA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: University of California, San Francisco, San Francisco, California, USA.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000368:Aged; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000032:analysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000652:urine*; D007684:Kidney Tubules / Q000473:pathology*; D000071068:Lipocalin-2 / Q000652:urine; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000652:urine*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D003404:Creatinine; D000118:Acetylglucosaminidase
keywords: chronic kidney disease; microalbuminuria; proteinuria