Urinary IgG4 and Smad1 Are Specific Biomarkers for Renal Structural and Functional Changes in Early Stages of Diabetic Nephropathy.

Abstract

Diabetic nephropathy (DN) is the major cause of end-stage kidney disease, but early biomarkers of DN risk are limited. Herein we examine urinary IgG4 and Smad1 as additional early DN biomarkers. We recruited 815 patients with type 2 diabetes; 554 patients fulfilled the criteria of an estimated glomerular filtration rate (eGFR) >60 mL/min and no macroalbuminuria at baseline, with follow-up for 5 years. Patients without macroalbuminuria were also recruited for renal biopsies. Urinary IgG4 and Smad1 were determined by enzyme-linked immunoassays using specific antibodies. The specificity, sensitivity, and reproducibility were confirmed for each assay. Increased urinary IgG4 was significantly associated with lower eGFR. The level of urinary IgG4 also significantly correlated with surface density of peripheral glomerular basement membrane (Sv PGBM/Glom), whereas Smad1 was associated with the degree of mesangial expansion-both classic pathological findings in DN. Baseline eGFR did not differ between any groups; however, increases in both urinary IgG4 and Smad1 levels at baseline significantly predicted later development of eGFR decline in patients without macroalbuminuria. These data suggest that urinary IgG4 and Smad1 at relatively early stages of DN reflect underlying DN lesions and are relevant to later clinical outcomes.

• Authors: Toshio Doi, Tatsumi Moriya, Yui Fujita, Naoto Minagawa, Masaru Usami, Tomoko Sasaki, Hideharu Abe, Seiji Kishi, Taichi Murakami, Motoshi Ouchi, Go Ichien, Keiichi Yamamoto, Hiroki Ikeda, Yasuhiko Koezuka, Norimichi Takamatsu, Kenji Shima, Michael Mauer, Kojiro Nagai, Tatsuya Tominaga
• Journal: Diabetes (Diabetes) Vol. 67 Issue 5 Pg. 986-993 (05 2018) ISSN: 1939-327X [Electronic] United States
• PMID: 29490904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by the American Diabetes Association.

Chemical References

• Biomarkers
• Immunoglobulin G
• SMAD1 protein, human
• Smad1 Protein

Topics

• Adult
• Biomarkers (urine)
• Diabetes Mellitus, Type 2 (complications, urine)
• Diabetic Nephropathies (diagnosis, etiology, pathology, urine)
• Early Diagnosis
• Enzyme-Linked Immunosorbent Assay
• Female
• Glomerular Basement Membrane (ultrastructure)
• Glomerular Filtration Rate
• Humans
• Immunoglobulin G (urine)
• Kidney (pathology)
• Male
• Mesangial Cells (ultrastructure)
• Microscopy, Electron
• Middle Aged
• Reproducibility of Results
• Sensitivity and Specificity
• Smad1 Protein (urine)