Captopril-induced reduction of serum levels of transforming growth factor-beta1 correlates with long-term renoprotection in insulin-dependent diabetic patients.
The renoprotective effect of captopril on progression of diabetic nephropathy was demonstrated by the Collaborative Study Group Captopril Trial and might be independent of blood pressure. Because angiotensin II is known to stimulate the prosclerotic cytokine, transforming growth factor-beta (TGF-beta), we postulated that the renoprotective effect may be due to inhibition of TGF-beta1 production. TGF-beta1 levels were measured in serum at baseline and 6 months from patients in the captopril trial. TGF-beta1 analyses were performed on all available patient sera. Analysis was performed between the percent change in TGF-beta1 levels during the first 6 months versus the percent change in glomerular filtration rate (GFR) in the subsequent 2 years. TGF-beta1 levels increased by 11% (P = 0. 003) in the placebo group (n = 24), whereas there was a decrease of 14% (P = 0.01) in the captopril group (n = 34). There was an inverse correlation between the percent change in TGF-beta1 levels during the first 6 months and the percent change in GFR over the ensuing 2-year period in patients from both the placebo (r = -0.55, P = 0. 005) and captopril groups (r = -0.45, P = 0.008). In patients with initial GFR below 75 mL/min, there was an even stronger correlation in percent change in TGF-beta1 levels and percent change in GFR in both placebo (n = 9, r = -0.69, P = 0.03) and captopril groups (n = 21, r = -0.73, P = 0.0001). Our data suggest that captopril decreases TGF-beta1 levels in diabetic nephropathy and that changes in TGF-beta1 levels may predict the course of diabetic nephropathy.
Sharma
K
K
Thomas Jefferson University, Philadelphia, PA 19107, USA. Kumar.Sharma@mail.tju.edu
Eltayeb
B O
BO
McGowan
T A
TA
Dunn
S R
SR
Alzahabi
B
B
Rohde
R
R
Ziyadeh
F N
FN
Lewis
E J
EJ
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage* / Q000009:adverse effects; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006977:Hypertension, Renal / Q000097:blood* / Q000188:drug therapy; D007677:Kidney Function Tests; D008297:Male; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002216:Captopril; D006442:Glycated Hemoglobin; D016212:Transforming Growth Factor beta