title: Urine Proteome Specific for Eye Damage Can Predict Kidney Damage in Patients With Type 2 Diabetes: A Case-Control and a 5.3-Year Prospective Cohort Study.
abstract: The predictive value of microalbuminuria (MAU) for kidney damage is limited in type 2 diabetes (T2D). We studied whether a urine proteome specific for sight-threatening proliferative diabetic retinopathy (PDR) is an indicator to predict chronic renal insufficiency (CRI) in patients with T2D.
  
  
  
  A shotgun urine proteomic analysis was performed in patients with MAU and PDR (case subjects) and in patients with MAU and a duration of T2D for >10 years but without any degree of retinopathy (control subjects). In the cohort study, 210 patients with T2D with an estimated glomerular filtration rate (eGFR) ≥80 mL/min/1.73 m2were followed for a median of 5.3 years. Urine proteins specific for PDR were used for predicting CRI (eGFR <60 mL/min/1.73 m2).
  
  
  
  The top two urine proteins with the highest difference in ratio of case subjects to control subjects were haptoglobin (8.7 times; P < 0.0001) and α-2-macroglobulin (5.7 times; P < 0.0001). In the cohort study, patients with baseline urinary haptoglobin ≥20 ng/min (haptoglobinuria) had a higher incidence of CRI than those without (hazard ratio [95% CI] 3.27 [1.41-7.58]; P = 0.006). The overall CRI rate was 3.2% for patients without haptoglobinuria or MAU, 9.5% for those with MAU, and 13.3% for those with haptoglobinuria. The highest rate for CRI (22.4%) was in patients with both MAU and haptoglobinuria (P < 0.001).
  
  
  
  Urine haptoglobin, which is specific for PDR, is a novel biomarker and complement to urine albumin for predicting kidney damage in patients with T2D.
authors.affiliation: Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China jkyang@ccmu.edu.cn.
authors.forename: Jin-Kui
authors.identifier: 0000-0002-7008-9229
authors.initials: JK
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Shi
authors.affiliation: Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Cao
authors.affiliation: Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Feng
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Endocrinology and Metabolism Department, Peking University People's Hospital, Beijing, China.
authors.forename: Li-Nong
authors.initials: LN
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000652:urine*; D003930:Diabetic Retinopathy / Q000150:complications / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006242:Haptoglobins / Q000652:urine; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000453:epidemiology* / Q000652:urine*
chemical_list: D015415:Biomarkers; D006242:Haptoglobins; D020543:Proteome