A closer look: ultrastructural evaluation of high-risk progression IgA nephropathy

ABSTRACT

This retrospective, cross-sectional study sought to examine the ultrastructural characteristics of glomerular lesions using Transmission Electron Microscopy (TEM) in IgA nephropathy (IgAN) and their relationship with the high risk of progression phenotype defined by KDIGO guideline as proteinuria ≥1 g/24 hours despite 3 months of optimized supportive care. We analyzed 81 IgAN patients (median age 41 years, 67% male, eGFR 43.8 mL/min, proteinuria 1.04 g/day); 42 (52%) of them had high risk of progression. There were no differences in terms of age, sex, comorbidities, eGFR, and hematuria between the two groups. High-risk patients more often had segmental glomerulosclerosis (29% vs 8%, p 0.01) in optical microscopy, while in TEM had more frequent podocyte hypertrophy (62% vs 26%, p 0.001) and podocyte foot process detachment from the glomerular basement membrane (19% vs 8%, p 0.05), more often thicker (19% vs 5%, p 0.05) and duplicated (26% vs 10%, p 0.05) glomerular basement membrane, and the presence of subendothelial and subepithelial deposits (31% vs 13%, p 0.05). However, in multivariate binary logistic regression analysis, only podocyte hypertrophy (OR 3.14; 95%CI 1.12, 8.79) was an independent risk factor for high-risk progression in IgAN. These findings highlight the importance of podocytopathy in IgAN progression.

KEYWORDS:

• High-risk progression IgA nephropathy
• IgA nephropathy
• Podocitopathy
• podocyte hypertrophy
• transmission electron microscopy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

G.S., G.T.B responsible for conceptualization, methodology and original draft preparation. G.T.B. pathology assessment and data recording; G.S., G.T.B carried out bibliographic research and data recording; G.S., G.T.B performed the statistical analysis. Both authors read and approved the final manuscript.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.