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. 2021 Apr;36(4):899-908.
doi: 10.1007/s00467-020-04772-4. Epub 2020 Oct 4.

Clinicopathological significance of glomerular capillary IgA deposition in childhood IgA nephropathy

Yuko Shima  1 , Koichi Nakanishi  2 , Hironobu Mukaiyama  1 , Yu Tanaka  1 , Takuzo Wada  1 , Ryojiro Tanaka  3 , Hiroshi Kaito  3 , Kandai Nozu  4 , Mayumi Sako  5 , Kazumoto Iijima  4 , Norishige Yoshikawa  6
Affiliations

Clinicopathological significance of glomerular capillary IgA deposition in childhood IgA nephropathy

Yuko Shima et al. Pediatr Nephrol. 2021 Apr.

Abstract

Background: IgA nephropathy (IgAN) is characterized by predominant mesangial IgA deposition. Some patients with IgAN demonstrate IgA deposition in glomerular peripheral capillaries (cap-IgA). The clinicopathological significance of cap-IgA remains incompletely investigated in children.

Methods: We retrospectively analyzed 503 consecutive cases of biopsy-proven childhood IgAN between July 1976 and June 2013 to compare clinical and pathological features between IgAN patients with and without cap-IgA.

Results: Among the 503 patients, 30 (6.0%) had cap-IgA. We found significant differences in proteinuria (2.0 vs. 0.5 g/day/m2, p < 0.0001), time from onset to kidney biopsy (2.2 vs. 8.3 months, p < 0.0001), and rate of proteinuria remission after treatment (23.3% vs. 48.0%, p = 0.007) between both groups. Pathological analysis revealed significant differences in M1 (83.3% vs. 56.0%, p = 0.002), ratio of subendothelial electron dense deposits (EDDs, 58.6% vs. 16.5%, p < 0.0001) and subepithelial EDDs (48.3% vs. 16.5%, p = 0.0001), and glomerular basement membrane (GBM) lysis (58.6% vs. 27.1%, p = 0.0006) between both groups. More than half of cap-IgA patients (17/30, 56.7%), whereas only 26.2% of non-cap-IgA patients (124/473), were treated with immunosuppressive treatments. Six of 30 cases (20%) with cap-IgA reached glomerular filtration rate (GFR) categories G3a-G5 (estimated GFR < 60 ml/min/1.73 m2) at most recent observation (mean observation period: 7.0 ± 4.0 years). According to Kaplan-Meier analysis, patients with cap-IgA had significantly lower kidney survival curves than non-cap-IgA patients (72.8% vs. 97.2% at 10 years, p < 0.0001).

Conclusions: Cap-IgA is associated with acute inflammation with GBM changes, resulting in refractory heavier proteinuria. Cap-IgA may represent a poor prognostic factor.

Keywords: Capillary IgA deposition; Children; Electron dense deposits; IgAN; Immunofluorescence; Kidney failure; School screening programs.

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