Prevalence of alpha1-antitrypsin phenotypes in patients with IgA nephropathy.
BACKGROUND
alpha1-antitrypsin (AAT) is the main protease inhibitor in the blood. Several different AAT phenotypes exist. The most common variant is the MM phenotype, which is also associated with normal AAT levels. The less common phenotypes with Z and S variants are associated with low AAT levels. AAT deficiency is a risk factor for pulmonary emphysema, liver impairment and some immune-mediated diseases, some of which are also associated with IgA nephropathy (IgAN). In fact, liver impairment resulting from AAT deficiency may directly contribute to renal abnormalities resembling IgAN.


METHODS
We investigated AAT phenotype and AAT levels in 100 IgAN patients who did not have end-stage liver disease. Fifteen patients in our sample had secondary IgAN. We also tested for the presence of renal deposition of AAT in patients heterozygous for AAT variants as well as in a randomly chosen group of patients with MM phenotype. We checked for any association between AAT phenotype and the progression of IgAN as well as the prevalence of diseases associated with IgAN (i.e. secondary IgAN).


RESULTS
Twelve patients in our sample were heterozygous for AAT variants. Phenotypes were MZ in 5 patients, MS in 3, MF in 1, ML in 2 and ME in 1 patient. AAT levels were lower in these 12 patients than in those homozygous for the M variant (1.17+/-0.46 vs. 1.44+/-0.34 g/l, p < 0.05). We found renal deposition of AAT in 2 heterozygous patients and in 1 of the 12 patients which were randomly chosen. End-stage renal (ESRF) failure developed in 3 of the 12 heterozygous patients and in 6 of the 88 homozygous patients (p = 0.07) during the follow-up. The prevalence of heterozygosity was significantly higher in patients with secondary IgAN than in those with primary IgAN ((5/15 vs. 7/85; p < 0.02).


CONCLUSIONS
AAT phenotype is not associated with the risk of primary IgA nephropathy, but might have an impact on disease outcome as well as on the risk of secondary IgAN.
Szönyi
L
L
1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Dobos
M
M
Vásárhelyi
B
B
Héninger
E
E
Vas
T
T
Nagy
J
J
Kovács
T
T
D000293:Adolescent; D000328:Adult; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000209:etiology; D006579:Heterozygote; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D010641:Phenotype; D015995:Prevalence; D000515:alpha 1-Antitrypsin / Q000032:analysis* / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000235:genetics
D000515:alpha 1-Antitrypsin