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ArticleClinical and experimental nephrology2026

Differential urinary IgG fragmentation in diabetes and IgA nephropathy.

Tomokazu Ohnishi, Yasuyuki Nagasawa, Taro Misaki, Norika Chiba, Tetsuya Matsuguchi

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Article in Clinical and experimental nephrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 authors.

Tomokazu OhnishiDepartment of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan. tomo@dent.kagoshima-u.ac.jp.ORCID http://orcid.org/0000-0002-7541-1934
Yasuyuki NagasawaDepartment of Internal Medicine, Hyogo Medical University, Nishinomiya, 663-8501, Japan. nagasawa@hyo-med.ac.jp.
Taro MisakiDivision of Nephrology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, 430-8558, Japan.
Norika ChibaDepartment of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.
Tetsuya MatsuguchiDepartment of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.

Funding

Japan Society for the Promotion of Science 23K09146Japan Society for the Promotion of Science London 20K09909Japan Society for the Promotion of Science London 23K09153
6 · The paper itself

Abstract

backgroundProteinuria 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.

methodsUrinary 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.

resultsIn 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.

conclusionDistinct 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.

Indexed as

Diabetes Mellitus, ExperimentalDiabetic NephropathiesGlomerulonephritis, IGAImmunoglobulin GAdultAlbuminuriaAnimalsBiomarkersCase-Control StudiesCathepsin BCathepsin DDisease ProgressionFemaleGlycated HemoglobinHumansKidney TubulesBiomarkersCathepsin BCathepsin DCTSB protein, humanGlycated HemoglobinImmunoglobulin GDiabetic nephropathyIgA nephropathyIgGProteinuria

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.