Tohoku J. Exp. Med., 2021 January, 253(1)

Urinary Thrombin as a Marker of Glomerular Inflammation Associated with Renal Injury in Type 2 Diabetes

Yasunori Kitamoto,¹ Takahisa Imamura,² Yoshio Taguma,³ Taisuke Iwaoka,⁴ Hoichi Yorinaka⁵ and Kenji Arizono⁶

¹Department of Laboratory Medicine, Sendai Shakaihoken Hospital/JCHO Sendai Hospital, Sendai, Miyagi, Japan
²Department of Molecular Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
³Department of Nephrology, Sendai Shakaihoken Hospital/JCHO Sendai Hospital, Sendai, Miyagi, Japan
⁴Department of Internal Medicine, Seijino Rehabilitation Hospital, Kumamoto, Kumamoto, Japan

⁵Department of Pharmacology and Molecular Therapeutics, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
⁶Department of Nephrology, Kumamoto Chuo Hospital, Kumamoto, Kumamoto, Japan

Glomerular inflammation is a putative aggravation factor for type 2 diabetic nephropathy and urinary thrombin is a novel marker of glomerular inflammation. To clarify the relationship between glomerular inflammation and progression of the nephropathy, we measured urinary thrombin in 118 patients with type 2 diabetic nephropathy at different stages. To investigate the implications of urinary thrombin in the nephropathy, we compared urinary thrombin with expression of tissue factor, the trigger of blood coagulation activation, in glomeruli and with markers of renal injury (estimated glomerular filtration rate (eGFR) and proteinuria). Urinary thrombin was found in 4.9% (3/61), 0.0% (0/12), 29.6% (8/27) and 50.0% (9/18) of patient groups at stages 1, 2, 3 and 4, respectively. Thus, urinary thrombin was negligible in the patients at early stages (stages 1 and 2), but was present predominantly in the patients at advanced stages (stages 3 and 4). Tissue factor was expressed in accumulated macrophages in glomeruli, which indicates that thrombin may be generated in inflamed glomeruli presumably via inflammation-induced activation of the exudated coagulation factors into glomerular tissues and then be excreted in urine. Urinary thrombin was significantly associated with both decreased eGFR and increased proteinuria in type 2 diabetic nephropathy. Therefore, increased urinary thrombin in patients with advanced stages of type 2 diabetic nephropathy suggests that glomerular inflammation may injure the tissues, thereby impairing renal function. Monitoring an effect of anti-diabetic treatments on glomerular inflammation in the patients with type 2 diabetic nephropathy may be a possible application of urinary thrombin.

Keywords —— advanced nephropathy; glomerular inflammation; tissue factor in macrophage; type 2 diabetes; urinary thrombin

© 2021 Tohoku University Medical Press

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Tohoku J. Exp. Med 2021 253, 41-49.

Correspondence: Yasunori Kitamoto, Department of Laboratory Medicine, Sendai Shakaihoken Hospital/JCHO Sendai Hospital, 3-16-1 Tsutsumi-machi, Aoba-ku, Sendai, Miyagi 981-8501, Japan.

e-mail: kitamotoyasunori@gmail.com