The level of galactose-deficient IgA1 in the sera of patients with IgA nephropathy is associated with disease progression

Abstract

Although high serum levels of galactose-deficient IgA1 (an important biomarker of IgA nephropathy (IgAN)) are found in most patients with IgAN, their relationship to disease severity and progression remains unclear. To help clarify this we prospectively enrolled 275 patients with IgAN and followed them for a median of 47 months (range 12-96 months). Serum galactose-deficient IgA1 was measured at the time of diagnosis using a lectin-based ELISA, and renal survival was modeled using the Cox proportional hazards method. The serum levels of galactose-deficient IgA1 were higher in patients with IgAN compared to those in healthy controls. Importantly, in adjusted analysis, higher levels of galactose-deficient IgA1 were independently associated with a greater risk of deterioration in renal function with a hazard ratio of 1.44 per standard deviation of the natural log-transformed galactose-deficient IgA1 concentration. In reference to the first quartile, the risk of kidney failure increased such that the hazard ratio for the second quartile was 2.47, 3.86 for the third, and 4.76 for the fourth quartile of the galactose-deficient IgA1 concentration. Hence, elevated serum levels of galactose-deficient IgA1 are associated with a poor prognosis in IgAN.

Figure 1. Renal survival in IgAN patients with four quartile serum Gd-IgA1 levels

The renal survival deteriorated by the quartile of serum Gd-IgA1 level. The time zero was kidney biopsy. The division between the four groups of patients was based on quartile of Gd-IgA1 level expressed as 236.5 U/ml, 312.5 U/ml, and 407.8 U/ml. The renal survival at the 1^st and 3^rd year in each group of patients was 100.0% and 96.9%; 100.0% and 91.8%; 100.0% and 92.2%; 98.6% and 88.6% respectively. (Log Rank test, p=0.004).