title: Proximal tubule dysfunction is dissociated from endothelial dysfunction in normoalbuminuric patients with type 2 diabetes mellitus: a cross-sectional study.
abstract: BACKGROUND
  The aim of our study was to clarify the hypothesis that proximal tubule (PT) dysfunction may be responsible for early diabetic nephropathy (DN), independently of preceding glomerular endothelial dysfunction. The pattern of endothelial dysfunction and its potential variability was evaluated in two vascular beds, the kidney and the brain.
  
  
  METHODS
  A total of 68 normoalbuminuric type 2 diabetes mellitus (DM) patients were enrolled in a cross-sectional study and the following parameters were assessed: urinary albumin:creatinine ratio (UACR), urinary α(1)-microglobulin, urinary β(2)-microglobulin, plasma asymmetric dimethyl-arginine (ADMA), serum creatinine, glomerular filtration rate (GFR), C-reactive protein (CRP), fibrinogen, HbA(1c); pulsatility and resistance indices in the internal carotid artery and middle cerebral artery and intima-media thickness (IMT) in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test.
  
  
  RESULTS
  Plasma ADMA was increased in 12 patients (17.5%), urinary α(1)-microglobulin in 19 patients (27.9%) and urinary β(2)-microglobulin in 16 patients (23.5%). Cerebral hemodynamic indices correlated with plasma ADMA, CRP, fibrinogen, duration of DM, HbA(1c) and GFR. ADMA correlated with fibrinogen, CRP, HbA(1c), duration of DM and GFR. There were no correlations between ADMA and UACR, and urinary α(1)-/β(2)-microglobulin. Also, no correlations were found between urinary α(1)-/β(2)-microglobulin and UACR, HbA(1c), duration of DM and GFR.
  
  
  CONCLUSIONS
  The increase in urinary α(1)-/β(2)-microglobulin precedes the stage of albuminuria. It may be assumed that early DN is related to PT dysfunction. Endothelial dysfunction plays a pivotal role in the brain vasculature, while its involvement in the development of early DN is not conditional on the occurrence of albuminuria.
authors.affiliation: Department of Nephrology, County Emergency Hospital, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. ligiapetrica@rdslink.ro
authors.forename: Ligia
authors.initials: L
authors.lastname: Petrica
authors.forename: Maxim
authors.initials: M
authors.lastname: Petrica
authors.forename: Adrian
authors.initials: A
authors.lastname: Vlad
authors.forename: Dragos Catalin
authors.initials: DC
authors.lastname: Jianu
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Gluhovschi
authors.forename: Calina
authors.initials: C
authors.lastname: Ianculescu
authors.forename: Catalina
authors.initials: C
authors.lastname: Firescu
authors.forename: Victor
authors.initials: V
authors.lastname: Dumitrascu
authors.forename: Sorin
authors.initials: S
authors.lastname: Giju
authors.forename: Cristina
authors.initials: C
authors.lastname: Gluhovschi
authors.forename: Flaviu
authors.initials: F
authors.lastname: Bob
authors.forename: Florica
authors.initials: F
authors.lastname: Gadalean
authors.forename: Sorin
authors.initials: S
authors.lastname: Ursoniu
authors.forename: Silvia
authors.initials: S
authors.lastname: Velciov
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Bozdog
authors.forename: Oana
authors.initials: O
authors.lastname: Milas
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged