Angiotensin converting enzyme insertion/deletion genetic polymorphism: its impact on renal function in critically ill patients.
OBJECTIVE
Previous clinical studies have suggested an association between the insertion/deletion (I/D) genetic polymorphism of angiotensin converting enzyme and acute or chronic diseases. We aimed to test the prognostic value of the I-allele, which is associated with lower angiotensin converting enzyme activity, on acute kidney injury.


METHODS
Prospective 6-month noninterventional study.


METHODS
Intensive care unit of a University Hospital.


METHODS
One hundred eighty consecutive admitted white patients for an expected intensive care unit stay >48 hr. Angiotensin converting enzyme genetic polymorphism was screened for genotype (I/D polymorphism analysis by polymerase chain reaction amplification) and phenotype (measurement of the circulating rate of angiotensin converting enzyme by spectrophotometry). Acute kidney injury was assessed according to Risk, Injury, Failure, Loss, and End-stage Kidney classification.


METHODS
None.


RESULTS
II, ID, and DD genotype frequencies were 25%, 48%, and 27%, respectively. II and ID genotypes were associated with lower baseline circulating rates of angiotensin converting enzyme (20 +/- 14 and 22 +/- 18 U/L, respectively, vs. 30 +/- 23 U/L for DD genotype; p = 0.04). Repartition of angiotensin converting enzyme genotypes were different in patients with and without acute kidney injury (p < 0.0001), with greater II genotype proportion in acute kidney injury patients (42% vs. 13% for those without acute kidney injury). After adjustment on the identified prognostic factors, II genotype was independently associated with increased risk of acute kidney injury (adjusted odds ratio, 6.5; 95% confidence interval, 2.4-17.7; p = 0.0002), then death among patients with acute kidney injury (adjusted odds ratio, 1.7; 95% confidence ratio, 1.1-2.6; p = 0.02).


CONCLUSIONS
These data confirm the key role of the renin-angiotensin system to maintain glomerular filtration rate, and highlight an association between a genetic factor and susceptibility to and prognosis of acute kidney disease.
du Cheyron
Damien
D
Service de Réanimation Médicale, UPRES EA2128, CHU de Caen, Caen, France. ducheyron-d@chu-caen.fr
Fradin
Sabine
S
Ramakers
Michel
M
Terzi
Nicolas
N
Guillotin
Damien
D
Bouchet
Bruno
B
Daubin
Cédric
C
Charbonneau
Pierre
P
D058186:Acute Kidney Injury / Q000235:genetics*; D016638:Critical Illness; D005260:Female; D005838:Genotype; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies
D007703:Peptidyl-Dipeptidase A