Glomerular hemodynamics and the renin-angiotensin system in patients with type 1 diabetes mellitus

Kidney Int. 2003 Jan;63(1):172-8. doi: 10.1046/j.1523-1755.2003.00701.x.

Abstract

Background: Many studies have reported that blocking the renin-angiotensin-system (RAS) with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker in the patient with diabetes mellitus leads to an increase in renal plasma flow (RPF), no change in glomerular filtration rate (GFR), and a fall in filtration fraction. This constellation is generally attributed to predominant efferent arteriolar dilation.

Methods: This study examined the renal hemodynamic response to blocking the RAS with both captopril and candesartan on separate days in 31 patients with type 1 diabetes mellitus.

Results: There was a wide range of changes in RPF and GFR in response to the two agents, each administered at the top of its dose-response range. The RPF response to the two agents was strongly concordant (r = 0.65; P < 0.001), as was the GFR response (r = 0.81; P < 0.001). Moreover, there was a strong correlation between the RPF response and the change in GFR with each agent (r = 0.83 and 0.66; P < 0.01). A significant rise in RPF was followed by a rise in GFR. The RPF dependency of GFR in the type 1 diabetics suggests strongly that glomerular filtration equilibrium exists in the glomeruli of the diabetic kidney: Simple notions of local control based on afferent:efferent arteriolar resistance ratios are too simplistic.

Conclusion: Our data suggest that the intrarenal RAS is activated in over 80% of patients with type 1 diabetes mellitus. Abundant evidence suggests that this activation predisposes to diabetic nephropathy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Antihypertensive Agents / administration & dosage
  • Benzimidazoles / administration & dosage
  • Captopril / administration & dosage
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / physiopathology*
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Kidney Glomerulus / blood supply*
  • Kidney Glomerulus / physiology
  • Male
  • Middle Aged
  • Renal Circulation / drug effects
  • Renal Circulation / physiology*
  • Renin-Angiotensin System / physiology*
  • Tetrazoles / administration & dosage

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Benzimidazoles
  • Tetrazoles
  • Captopril
  • candesartan