Serum Galactose-Deficient IgA1 Level Is Not Associated with Proteinuria in Children with IgA Nephropathy

Introduction. Percentage of galactose-deficient IgA1 (Gd-IgA1) relative to total IgA in serum was recently reported to correlate with proteinuria at time of sampling and during follow-up for pediatric and adult patients with IgA nephropathy. We sought to determine whether this association exists in another cohort of pediatric patients with IgA nephropathy. Methods. Subjects were younger than 18 years at entry. Blood samples were collected on one or more occasions for determination of serum total IgA and Gd-IgA1. Gd-IgA1 was expressed as serum level and percent of total IgA. Urinary protein/creatinine ratio was calculated for random specimens. Spearman’s correlation coefficients assessed the relationship between study variables. Results. The cohort had 29 Caucasians and 11 African-Americans with a male？:？female ratio of 1.9？:？1. Mean age at diagnosis was 11.7 ± 3.7 years. No statistically significant correlation was identified between serum total IgA, Gd-IgA1, or percent Gd-IgA1 versus urinary protein/creatinine ratio determined contemporaneously with biopsy or between average serum Gd-IgA1 or average percent Gd-IgA1 and time-average urinary protein/creatinine ratio. Conclusion. The magnitude of proteinuria in this cohort of pediatric patients with IgA nephropathy was influenced by factors other than Gd-IgA1 level, consistent with the proposed multi-hit pathogenetic pathways for this renal disease. 1. Introduction IgA nephropathy (IgAN) is the most common form of chronic glomerulonephritis for individuals of European and Asian descent [1, 2]. The level of proteinuria at diagnosis of IgAN has been associated with the primary endpoint of outcome (i.e., progression to chronic dialysis or transplantation) in adults [3–7] and children [8–11]. Data from clinical and basic research in IgAN has led to the hypothesis that four hits are responsible for clinical expression of IgAN [12]. The first hit is the presence of aberrantly glycosylated O-linked glycans on the heavy-chain hinge region of circulatory IgA1 that terminate in N-acetylgalactosamine (GalNAc) rather than galactose [13]. Elevated serum levels of this galactose-deficient IgA1 (Gd-IgA1) were found in 76% of 153 Caucasian adults with IgAN in the United States [14]. IgAN patients in Japan and China also had elevated serum Gd-IgA1 levels [15, 16], as did African-American patients in the southeastern United States [17]. In addition, elevated serum Gd-IgA1 levels were found in 77% of 22 African-American and Caucasian children with IgAN [18]. The second hit is the induction of circulating IgG or IgA