Angiotensin-converting enzyme genotype and outcome in pediatric IgA nephropathy.
Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated as a genetic marker for progression of glomerular disease. Studies of ACE genotypes in adults with IgA nephropathy (IgAN) have yielded conflicting results. We performed ACE genotyping on 79 patients with IgAN diagnosed prior to age 18 years who had either progressed to end-stage renal disease (ESRD) or are now more than 5 years post biopsy. Mean follow-up was 14.8 years for those with normal renal function. Forty-three (54.4%) subjects had normal renal function and a normal urinalysis at last evaluation. Sixteen (20%) progressed to ESRD and 1 has chronic renal insufficiency. Kaplan-Meier survival curves for progression to ESRD did not differ significantly for the ACE DD, ID, and II genotype groups (P=0.095, log-rank test). By univariate analysis, presence of hypertension and degree of proteinuria at diagnosis, and unfavorable histology but not ACE genotype, was significantly associated with progression to ESRD. In the Cox proportional hazards model that included grade of proteinuria, the ACE D allele was a significant independent predictor of outcome with a hazard ratio of 2.37 (P=0.031). Our data, while inconclusive, suggest that the ACE D allele may associate with poor outcome in pediatric IgAN.
Santos
Noel M Delos
NM
Children's Foundation Research Center at the Le Bonheur Children's Medical Center, University of Tennessee Health Sciences Center, Memphis, USA.
Ault
Bettina H
BH
Gharavi
Ali G
AG
Kritchevsky
Stephen B
SB
Quasney
Michael W
MW
Jackson
Elizabeth C
EC
Fisher
Kimberly A
KA
Woodford
Susan Y
SY
Mitchell
Bonnie L
BL
Gaber
Lillian W
LW
Arheart
Kristopher L
KL
Wyatt
Robert J
RJ
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000401:mortality; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000235:genetics / Q000401:mortality; D016019:Survival Analysis
D005819:Genetic Markers; D007703:Peptidyl-Dipeptidase A