Angiotensin I-converting enzyme genotype significantly affects progressionof IgA glomerulonephritis in an Italian population

To evaluate the role of angiotensin-converting enzyme (ACE) gene insertion/ deletion (I/D) polymorphism in the progression of immunoglobulin A glomerul onephritis (IgA-GN), genotype distribution in 81 biopsy-proven cases of ISA -GN was studied. A logistic regression model showed that the risk for homoz ygous DD was not significantly elevated in patients with IgA-GN compared wi th healthy subjects (odds ratio = 1.16; confidence interval [CI], 0.4 to 3. 3). However, the 5-year (78% v 90%) and 10-year (52% v 82%) renal survival rates for 47 patients with serum creatine (Cr) levels of 1.5 mg/dL or less at biopsy was significantly less in DD patients (n = 18; chi(2) = 5.41; P = 0.02). The hazard ratio (HR) for DD (multivariate analysis from Cox propor tional model after adjustment for known factors of progression, such as hyp ertension [HPT] and proteinuria [PTO]) was 3.07 (CI, 1.1 to 9.4). The HR fo r heavy PTO was 6.1 (CI, 1.9 to 19). The association of DD genotype with pr ogression was even more striking when patients with other risk factors (hea vy proteinuria) were excluded, as shown by DD-related risk in the absence ( HR = 3.6; CI, 1.1 to 12) and presence (HR = 2; CI, 0.4 to 10) of PTO. The r isk ratio was further increased by the coexistence of DD + PTO (HR = 9.16; CI, 1.8 to 15.7). Furthermore, in a cross-sectional study among patients wi th IgA-GN, a logistic regression model showed that the risk for homozygous DD was greater, although not at a statistically significant level in the en d-stage renal failure subgroup compared with the normal renal function subg roup (odds ratio = 3.16; CI, 0.7 to 13.7) after adjustment by sex, age at b iopsy, HPT, PTO, and therapy. Last, DD was significantly more frequent in t hose patients who started hemodialysis at an earlier age (chi(2) for trend = 6.81; P = 0.009). Our study further supports that ACE genotype is a risk factor not for the development, but for the worsening of IgA-GN clinical co urse. However, on the basis of current knowledge, we can not exclude that I /D polymorphism may simply serve as a prognostic marker, eventually linked with other discrete loci involved in the progression of renal damage. (C) 1 999 by the National Kidney Foundation, Inc.