Angiotensin-converting enzyme inhibitor withdrawal and ACE gene polymorphism.
OBJECTIVE
Withdrawal of angiotensin-converting enzyme (ACE) inhibitors may affect the progression of chronic renal failure and an insertion/deletion (I/D) polymorphism of the ACE gene may influence it.


METHODS
We retrospectively collected patients with chronic glomerulonephritis and benign nephrosclerosis who discontinued ACE inhibitor use. The relationship between the decline of renal function after the withdrawal and the influencing factors such as ACE gene polymorphism, blood pressure and proteinuria were evaluated using multiple regression analysis.


RESULTS
Forty-two patients (initial serum creatinine 0.5 - 6.5 mg/dl) had been treated and discontinued ACE inhibitor use. Only patients with the II or DI genotypes of the ACE gene developed the deterioration of renal function, starting at 2 months after the withdrawal. Stepwise regression analysis revealed that the level of proteinuria after the withdrawal, presence of the insertion of ACE gene and serum creatinine level at the time of withdrawal mainly influenced the decline of renal function after the withdrawal (adjusted R2 = 0.48).


CONCLUSIONS
Withdrawal of ACE inhibitor causes the deterioration of renal function in patients with the II or DI genotypes, high proteinuria after the withdrawal, and high serum creatinine level at the withdrawal, which probably causes the rebound increase in serum ACE activity.
Nonoguchi
H
H
Third Department of Internal Medicine, Kumamoto University School of Medicine, Japan. nono@kaiju.medic.kumamoto-u.ac.jp
Kiyama
S
S
Inoue
H
H
Nakayama
Y
Y
Inoue
T
T
Kohda
Y
Y
Machida
K
K
Tajima
A
A
Kitamura
K
K
Miyoshi
T
T
Shimada
H
H
Shimada
H
H
Tajiri
M
M
Honda
Y
Y
Tanaka
M
M
Tomita
K
K
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000235:genetics; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A