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


CONCLUSIONS
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.
Hollenberg
Norman K
NK
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. djpagecapo@rics.bwh.harvard.edu
Price
Deborah A
DA
Fisher
Naomi D L
ND
Lansang
M Cecilia
MC
Perkins
Bruce
B
Gordon
Michael S
MS
Williams
Gordon H
GH
Laffel
Lori M B
LM
D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D002216:Captopril / Q000008:administration & dosage; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D013777:Tetrazoles / Q000008:administration & dosage
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D002216:Captopril; C081643:candesartan