Low-responders to angiotensin II receptor blockers and genetic polymorphism in angiotensin-converting enzyme.
OBJECTIVE
The existence of low-responders to angiotensin II receptor blockers (ARBs) in terms of the preservation of renal function is reported here. We investigated the relationship between the responsiveness to ARBs and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene.


METHODS
The effects of ARBs on proteinuria and the progression of chronic renal failure were examined in 113 patients with chronic kidney disease for 34 months before and 27 months after the addition of ARBs.


RESULTS
Although a decrease in blood pressure was seen in the II, DI and DD patient subgroups of the ACE gene, the decrease in proteinuria and the amelioration of loss of renal function were observed in the II and DI but not in the DD patients. Kaplan-Meier analysis was employed with a decrease of the reciprocal of serum creatinine of more than 0.2, the induction of renal replacement therapy or death as endpoints. The analysis comparing the periods before and after the addition of ARBs revealed the extension of time to an end-point by the addition of ARBs in all groups together (II + DI + DD), in Group II, and Group DI but not in the DD patient Group.


CONCLUSIONS
These data suggest that DD patients with ACE gene demonstrate diminished response to ARBs in terms of renoprotection and that ACE gene polymorphism needs to be taken into account when using ARBs as a means of renoprotective therapy.
Nonoguchi
H
H
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. nono@kumamoto-u.ac.jp
Nakayama
Y
Y
Shiigai
T
T
Inoue
T
T
Inoue
H
H
Kohda
Y
Y
Honda
Y
Y
Tomita
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A