Study Highlights Serum Gd-IgA1 as Potential Prognostic Biomarker for IgA Nephropathy

Despite the significant role O-glycosylation status plays in the pathophysiology of IgA nephropathy (IgAN), findings from a recent study suggest the role of galactose-deficient IgA1 (Gd-IgA1) as a biomarker for risk of disease progression may merit further research.¹

Results of the systematic review and meta-analysis were published in Journal of Nephrology and showed serum Gd-IgA1 levels were not associated with validated prognostic risk factors but were negatively correlated with kidney function based on estimated glomerular filtration rate (eGFR).¹

A chronic kidney disease that progresses over time and can eventually lead to end-stage renal disease, IgAN is caused by deposits of IgA in the glomeruli and often goes unnoticed in its earlier stages. Its clinical course varies from patient to patient, underscoring the importance of Identifying patients at greatest risk of progressive kidney failure. Accordingly, there is a need for new biomarkers in IgAN to improve prognostication, treatment selection, and monitoring response to treatment.^1,2

“The utility of Gd-IgA1 levels to predict prognosis is unclear with a number of conflicting studies,” Pedro Alves Soares Vaz de Castro, a medical student at the Federal University of Minas Gerais, and colleagues wrote.¹

To examine the value of serum Gd-IgA1 as a biomarker in IgAN, investigators assessed its association with clinical, laboratory, and histopathological features of IgAN through a systematic review and meta-analysis. A literature search was conducted in PubMed, Web of Science, Cochrane, and Scopus using the keywords “IgA Nephropathy”, “Berger’s Disease”, “Immunoglobulin A nephropathy” and similar entry terms. Observational studies, including case-control, cohort, and cross-sectional studies, as well as clinical trials were included.¹

For inclusion, studies were also required to enroll participants with a kidney biopsy-confirmed diagnosis of primary IgAN in whom Gd-IgA1 levels had been measured. Articles published in English, Spanish, French, and Portuguese were eligible for inclusion. Investigators excluded studies investigating kidney diseases other than IgAN and recurrent IgAN after kidney transplant.¹

The initial search yielded 1986 studies, of which 47 were selected for full-text reading after screening the title and abstract and 1938 were excluded due to duplication or not including the study question. A total of 29 studies conducted between 2005 and 2022 ultimately met the eligibility criteria and were included in the systematic review.¹

Of the included studies, 4 (13.7%) were case-control, 14 (48.2%) were cohort, and 11 (37.9%) were cross-sectional. The studies were from 10 different countries, including China (31.0%), Japan (31.0%), and the United States (17.2%). Investigators noted all studies measured Gd-IgA1 levels using an enzyme-linked immunosorbent assay, although the technique varied among studies. Additionally, they pointed out a single study measured Gd-IgA1 levels with liquid chromatography-mass spectrometry.¹

Upon analysis, there was no significant difference in serum Gd-IgA1 levels between male and female patients with IgAN. Although 3 studies reported a positive correlation between age and Gd-IgA1 levels, the meta-analysis found no such association.¹

Investigators noted the association between Gd-IgA1 levels and hypertension, hematuria, and proteinuria were inconsistent. However, despite not being associated with several validated prognostic factors, they called attention to a notable negative correlation between serum Gd-IgA1 and eGFR (r = -0.19; P <.05).¹

Investigators were also careful to note several potential limitations to these findings, including the comparison of studies employing different methods of measuring serum levels of Gd-IgA1 and questionable quality of studies, especially in terms of comparability between groups, that may have led to biases that contributed to the variability of the results.¹

Nonetheless, investigators concluded that “Serum Gd-IgA1 levels were inconsistently associated with the risk of progressive loss of kidney function, however, there are sufficient data to justify continued evaluation of Gd-IgA1 as a prognostic biomarker in IgAN.”

References:

1. ^{Vaz de Castro PAS, Amaral AA, Almeida MG, et al. Examining the association between serum galactose-deficient IgA1 and primary IgA nephropathy: a systematic review and meta-analysis. J Nephrol (2024). https://doi.org/10.1007/s40620-023-01874-8}
2. ^{Johns Hopkins Medicine. Immunoglobulin A (IgA) Nephropathy. Conditions and Diseases. Accessed April 26, 2024. https://www.hopkinsmedicine.org/health/conditions-and-diseases/immunoglobulin-a-iga-nephropathy}