Effect of angiotensin-converting enzyme inhibition on renal function and albuminuria in normotensive type I diabetic patients.
Normotensive patients with insulin-dependent (type I) diabetes mellitus (n = 18) were given 25 mg captopril (b.i.d.) and placebo for 3 mo in a randomized double-blind crossover study. Patients had normal renal function, and none had retinopathy. Albuminuria was less than 20 micrograms/min in 12 patients and between 20 and 200 micrograms/min in the other 6. Patients were examined at the end of the placebo and captopril phases. Captopril caused little reduction in blood pressure obtained by 24-h ambulatory monitoring (systolic 126.0 +/- 2.7 to 123.9 +/- 2.4 mmHg, P less than 0.08; diastolic 74.2 +/- 1.9 to 72.1 +/- 1.9 mmHg, P less than 0.09). Captopril lowered glomerular filtration rate from 99.5 +/- 7.7 to 71.0 +/- 5.5 ml.min-1. 1.73 m-2 (P less than 0.01), whereas renal plasma flow (443.9 +/- 15.2 ml.min-1. 1.73 m-2) remained unchanged. Filtration fraction was reduced from 22.4 +/- 1.4 to 17.4 +/- 1.4% (P less than 0.01). Urinary albumin excretion was reduced from 59.1 +/- 0.15 to 27.7 +/- 13.9 micrograms/min (P less than 0.1). Reduction was related to the extent of initial albuminuria (r = 0.997, P less than 0.001), a relationship that remained significant after logarithmic transformation (r = 0.540, P less than 0.02). Dextran clearance was used to determine glomerular capillary function. Angiotensin inhibition caused reduction in effective glomerular pore size and also reduced flow via the nondiscriminatory shunt. Angiotensin inhibition in normotensive patients with type I diabetes was well tolerated. Reduction in albuminuria is mediated by a combination of hemodynamic changes and alterations in glomerular capillary function.
Wiegmann
T B
TB
Department of Medicine, University of Kansas Medical Center, Kansas City.
Herron
K G
KG
Chonko
A M
AM
MacDougall
M L
ML
Moore
W V
WV
D000328:Adult; D000419:Albuminuria; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002216:Captopril / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D012079:Renal Circulation / Q000187:drug effects*
D002216:Captopril; D006442:Glycated Hemoglobin