title: Transcapillary escape rate of albumin is increased and related to haemodynamic changes in normo-albuminuric type 1 diabetic patients.
abstract: OBJECTIVE
  An increase in urinary albumin excretion (UAE) in type 1 diabetic patients might reflect changes in vascular permeability and/or local haemodynamic factors. Indeed, transcapillary escape of albumin (TERalb), a measure of systemic capillary efflux, is increased in diabetic patients, even in those with a modest increase of albuminuria. In normo-albuminuric type 1 diabetic patients, systemic capillary and glomerular flow is increased. We hypothesized that these haemodynamic changes contribute to an elevated TERalb, even in the phase preceding micro-albuminuria.
  
  
  METHODS
  We measured TERalb in 39 normo-albuminuric type 1 diabetic patients and 46 healthy controls. TERalb was calculated from the disappearance curve of 125I-albumin. Renal and systemic haemodynamics were measured by standard techniques. Forearm blood flow (FBF) was measured by plethysmography. Endothelial function was assessed by intra-arterial infusion of acetylcholine. The structural integrity of the vessel wall was determined by the post-occlusive reactive hyperaemia test.
  
  
  RESULTS
  TERalb was increased in diabetic patients (5.53+/-0.40 versus 4.39+/-0.21 %/h, P = 0.01). Patients were divided into tertiles with respect to their TERalb. There were no differences in UAE, blood pressure, metabolic parameters, endothelial function or maximal vasodilatation after occlusion between the groups. However, filtration fraction and FBF were significantly increased in the group of diabetic patients with the highest levels of TERalb. Overall, in diabetic patients, FBF was significantly correlated with TERalb.
  
  
  CONCLUSIONS
  TERalb is increased in normo-albuminuric type 1 diabetic patients. In these patients with an increased capillary permeability, there is no evidence of endothelial dysfunction or vessel wall damage. However, both FBF and filtration fraction are increased. Therefore, the increased vascular permeability in the early phase of type 1 diabetes is associated with general haemodynamic alterations. Notably, such an increase in vascular permeability is not necessarily reflected by abnormal UAE. This could be due to either a lack of change in glomerular permeability or due to the fact that the threshold for tubular reabsorption of albumin has not been exceeded.
authors.affiliation: Department of Internal Medicine, University Hospital Nijmegen, The Netherlands. G.Vervoort@aig.azn.nl
authors.forename: G
authors.initials: G
authors.lastname: Vervoort
authors.forename: J A
authors.initials: JA
authors.lastname: Lutterman
authors.forename: P
authors.initials: P
authors.lastname: Smits
authors.forename: J H
authors.initials: JH
authors.lastname: Berden
authors.forename: J F
authors.initials: JF
authors.lastname: Wetzels
mesh_terms: D000328:Adult; D002199:Capillary Permeability; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D006801:Humans; D008297:Male; D012039:Regional Blood Flow; D012079:Renal Circulation; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism*
chemical_list: D012709:Serum Albumin