Serum and urine galactose deficient-Iga1 as biomarkers to predict progression of Iga Nephropathy

Introduction: IgA nephropathy (IgAN) is a kidney disease characterised by the deposition of immune complexes containing galactose deficient IgA1 in the glomeruli, leading to inflammation and progressive kidney damage. Accurate prediction of disease progression is crucial for determining the optimal treatment strategies and patient management. The recent 2021 Kidney Disease: Improving Global Outcome (KDIGO) guideline recommends the International IgA Nephropathy Prediction Tool for predicting the risk of disease progression in patients with IgAN. This tool however, has several limitations including its dependence on kidney biopsy, which is an invasive procedure. The tool has also been shown to overestimate the risk of progression in some ethnicities, underestimate the risk in some and is yet to be evaluated in others, including Malaysians. Thus, the search for sensitive, specific and non-invasive biomarkers arises. Aim: This study investigated the potential of Galactose Deficient Immunoglobulin A1 (Gd-IgA1) as a predictive biomarker for the progression of IgAN to end-stage kidney disease (ESKD). Method: Sixty respondents (twenty IgAN patients, non-IgAN patients and healthy individuals each) were enrolled from Hospital Sultan Idris Shah (HSIS) and Hospital Sultan Abdul Aziz Shah (HSAAS). Both blood and urine samples were collected from each participant for measurement of serum and urine Gd-IgA1, serum creatinine, and urine protein creatinine index (UPCI). The level of Gd-IgA1 was measured using enzyme-linked immunosorbent assay (ELISA) method. Results: Findings revealed that the concentration of Gd-IgA1 in serum samples of IgAN patients was significantly higher than those in non-IgAN patients [11.42 (5.87 -20.06) vs. 5.68 (2.96 – 11.45) µg/ml, p <0.001] and healthy respondents [11.42 (5.87 -20.06) vs. 5.36 (3.40 – 7.90) µg/ml p = 0.005]. Urine Gd-IgA1 was significantly higher in IgAN than healthy participants [41.77 (8.81 – 79) vs. 6.76 (2.19 – 10.83) ng/ml, p = 0.003) but the difference with non-IgAN [41.77 (8.81 – 79) vs. 27.81 (1.44 – 121.60) ng/ml] was not statistically significant (p = 0.991). There was a strong significant negative correlation between both serum and urine Gd-IgA1 and eGFR (rho = -0.70). There was a moderate correlation between UPCI and urine Gd-IgA1 (rho = 0.67) and a fair association with serum Gd-IgA1 (rho = 0.48). Regression analyses conducted to assess the independent predictive value of Gd-IgA1 showed that Gd-IgA1 did not predict progression to ESKD. Conclusion: Gd-IgA1 differentiates IgAN from other glomerulonephritis and is associated with disease severity in IgAN but does not independently predict progression to ESKD.

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