title: Renal tubular damage may contribute more to acute hyperglycemia induced kidney injury in non-diabetic conscious rats.
abstract: OBJECTIVE
  Growing evidences suggest that acute hyperglycemia is strongly related to kidney injury. Our study aimed to investigate the effects of acute hyperglycemia on kidney glomerular and tubular impairment in non-diabetic conscious rats.
  
  
  METHODS
  Non-diabetic conscious rats were randomly subjected to 6h of saline (control group) or high glucose (acute hyperglycemia group) infusion. Blood glucose was maintained at 16.0-18.0 mmol/L in acute hyperglycemia group. Renal structure and function alterations, systemic/renal inflammation and oxidative stress markers were assessed, and apoptosis markers of renal inherent cells were evaluated.
  
  
  RESULTS
  Acute hyperglycemia caused significant injury to structure of glomerular filtration barrier, tubular epithelial cells and peritubular vascular endothelial cells. It increased urinary microalbumin (68.01 ± 27.09 μg/24h vs 33.81 ± 13.81 μg/24h , P=0.014), β2-microglobulin, Cystatin C, urinary and serous neutrophil gelatinase-associated lipocalin levels (P < 0.05). Acute hyperglycemia decreased megalin and cubilin expression, activated systemic and renal oxidative stress as well as inflammation and promoted renal inherent cell apoptosis.
  
  
  CONCLUSIONS
  Acute hyperglycemia causes significant injury to kidney function and structure. Compared with damages of glomerular filtration barrier, renal tubular injury may contribute more to acute hyperglycemia induced proteinuria. Activation of inflammation especially renal inflammation, oxidative stress and enhanced apoptosis may be the underlying mechanisms.
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Nephropathy, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Jun-Ya
authors.initials: JY
authors.lastname: Jia
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xin-Rong
authors.initials: XR
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Yue
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Chen
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Shan
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Miao-Yan
authors.initials: MY
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China. Electronic address: changbc1970@126.com.
authors.forename: Bao-Cheng
authors.initials: BC
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D001786:Blood Glucose / Q000032:analysis; D060730:Glomerular Filtration Barrier / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D015309:Glucose Clamp Technique; D006943:Hyperglycemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D007684:Kidney Tubules / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D009393:Nephritis / Q000209:etiology; D009928:Organ Specificity; D018384:Oxidative Stress; D011507:Proteinuria / Q000209:etiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000209:etiology* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D001786:Blood Glucose
keywords: Acute hyperglycemia; Hyperglycemic clamp; Inflammation; Oxidative stress; Renal tubular impairment; Urinary microalbumin