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Clinical and Experimental Nephrology

Differential urinary IgG fragmentation in diabetes and IgA nephropathy

Published in:
Authors
Tomokazu Ohnishi
Yasuyuki Nagasawa
Taro Misaki
Norika Chiba
Tetsuya Matsuguchi
Published in
Clinical and Experimental Nephrology | Issue 3/2026

Abstract

Background

Proteinuria is a key marker of chronic kidney disease, notably in diabetic nephropathy (DN) and IgA nephropathy (IgAN). This study examined urinary IgG fragmentation and its link to disease progression.

Methods

Urinary IgG fragments were analyzed via western blot in diabetic mice and human subjects (controls: n = 7; diabetics: n = 14; IgAN: n = 15). Mouse and human IgG cleavage with renal tubular and glomerular fractions was performed in the presence or absence of protease inhibitors. Urinary cathepsin B activity was also measured.

Results

In diabetic mice, a 31-kDa IgG fragment appeared in the urine before the onset of albuminuria. This process was mediated by cathepsin D in the tubular fraction. Analysis of human subjects showed that fragmented IgG, especially the 47 kDa fragment, was increased in the urine of diabetic patients and correlated with elevated glycated hemoglobin (HbA1c) levels, but not in IgAN patients. Cathepsin B generated the IgG fragment by the tubular fraction, and its urinary activity was lower in IgAN patients than in diabetics.

Conclusion

Distinct patterns of IgG fragmentation and cathepsin B activity in DN versus IgAN suggest urinary IgG fragments may serve as early biomarkers and reflect disease-specific proteolytic pathways.
Title
Differential urinary IgG fragmentation in diabetes and IgA nephropathy
Authors
Tomokazu Ohnishi
Yasuyuki Nagasawa
Taro Misaki
Norika Chiba
Tetsuya Matsuguchi
Publication date
22-12-2025
Publisher
Springer Nature Singapore
Published in
Clinical and Experimental Nephrology / Issue 3/2026
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-025-02805-6
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