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Abstract: TH-PO530

Elevated Serum Gd-IgA1/s.IgA Levels and Not Serum Gd-IgA1 Alone Is an Independent Risk Factor for Composite Outcome in South Asian IgA Nephropathy (IgAN)

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Alexander, Suceena, Christian Medical College Vellore, Vellore, Tamil Nadu, India
  • Mani, Selvin Sundar Raj, Christian Medical College Vellore, Vellore, Tamil Nadu, India
  • Varughese, Santosh, Christian Medical College Vellore, Vellore, Tamil Nadu, India
  • John, George, Christian Medical College Vellore, Vellore, Tamil Nadu, India

Group or Team Name

  • GRACE-IgANI.
Background

The role of serum Gd-IgA1 in a prospective longitudinal South Asian IgAN cohort (GRACE-IgANI) and the impact of immunosuppression is not known.

Methods

We measured serum galactose-deficient IgA1 (s.Gd-IgA1) levels in 170 IgAN patients, 40 disease controls, and 27 healthy controls by KM55 ELISA (IBL international GmBH, Germany) at baseline. Longitudinal measurements were made at 1 year and 2 years in a subgroup of 117 IgAN patients who received a short course of immunosuppression. The baseline associations and the usefulness of s.Gd-IgA1 as a diagnostic and prognostic biomarker was assessed.

Results

s.Gd-IgA1 had significant positive correlation with serum immunoglobulin A (s.IgA) (r=0.6, n=170, p<0.001). Neither s.Gd-IgA1 nor s.Gd-IgA1/s.IgA ratio was a diagnostic marker for IgAN. s.Gd-IgA1/s.IgA ratio had stronger baseline and longitudinal associations than s.Gd-IgA1 alone. Elevated s.Gd-IgA1/s.IgA ratio was significantly associated with baseline clinical and histopathological indices of activity and chronicity. In the subgroup that received immunosuppression, there was significant decrease in both s.Gd-IgA1 and s.IgA at 1 year . The mean time to the composite outcome was significantly shorter for each quartile increase in s.Gd-IgA1/s.IgA ratio by Kaplan-Meier survival analysis [<1.3: vs. 1.3-1.7 HR 3.3 (95% CI 1.2-9.1), 1.7-2.3 HR 4.3 (95% CI 1.6-11.9), >2.3 HR 6.2 (95% CI 2.4-16.2), p<0.001]. Higher median s.Gd-IgA1/s.IgA ratio was as an independent predictor for composite outcome by Cox proportional-hazards (HR 2.3, 95% C.I. 1.2-4.5, p=0.01) model and outperformed 24-hour urine protein.

Conclusion

We have shown for the first time in IgAN with South Asian ethnicity, the relevance of proportion of s.Gd-IgA1 to total serum IgA for risk stratification, its association with prognosis and its longitudinal changes with immunosuppression . The results need to be externally validated.

Funding

  • Government Support – Non-U.S.