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Hypertension increases urinary excretion of immunoglobulin G, ceruloplasmin and transferrin in normoalbuminuric patients with type 2 diabetes mellitus

Ohara, Nobumasaa; Hanyu, Osamua; Hirayama, Satoshib; Nakagawa, Osamuc; Aizawa, Yoshifusaa; Ito, Seikia; Sone, Hirohitoa


In Figure 1 of this paper [1], the lower panel middle graph y-axis caption was incorrectly published as ‘U-CRL/Cr (μg/gCr)’. The correct caption should read, ‘U-A2/Cr (μg/gCr)’.

Additionally, in figure legends, ’a2-macroglobulin’ should read, ‘α2-macroglobulin’.

Journal of Hypertension. 34(7):1446, July 2016.

doi: 10.1097/HJH.0000000000000019

Objective: Increased urinary excretion of certain plasma proteins, such as immunoglobulin G (IgG), ceruloplasmin and transferrin, with different molecular radii of 55 Å or less and different isoelectric points have been reported to precede development of microalbuminuria in patients who have diabetes mellitus with hypertension. We examined how hypertension affects these urinary proteins in a diabetic state.

Methods: Excretion of IgG, ceruloplasmin, transferrin, albumin, α2-macroglobulin with a large molecular radius of 88 Å and N-acetylglucosaminidase in first-morning urine samples were measured in normoalbuminuric patients (urinary albumin-to-creatinine ratio < 15 mg/g) with hypertension and nondiabetes mellitus (group hypertension, n = 32), type 2 diabetes mellitus and normotension (group diabetes mellitus, n = 52) and type 2 diabetes mellitus and hypertension (group Both, n = 45), and in age-matched controls (n = 72).

Results: Urinary IgG, ceruloplasmin, transferrin, albumin and N-acetylglucosaminidase and estimated glomerular filtration rate (eGFR) were significantly elevated in groups diabetes mellitus and Both compared with controls. Furthermore, urinary IgG, ceruloplasmin and transferrin in group Both were significantly higher than those in group diabetes mellitus. These exhibited a positive and relatively strong association with eGFR compared with controls. No significant difference in urinary albumin or N-acetylglucosaminidase was found between the two diabetic groups. In contrast, group hypertension had elevated urinary transferrin without any changes in the other compounds. Urinary α2-macroglobulin did not differ among the four groups.

Conclusion: These findings suggest that normoalbuminuric diabetic patients without hypertension have both glomerular hemodynamic changes such as increased intraglomerular hydraulic pressure and altered proximal tubules, and that hypertension increases intraglomerular hydraulic pressure. Increased urinary IgG, ceruloplasmin and transferrin may reflect an increase in intraglomerular hydraulic pressure.

aDepartment of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata

bDepartment of Clinical Laboratory Medicine, Juntendo University School of Medicine, Tokyo

cDepartment of Endocrinology and Metabolism, Sanjo General Hospital, Niigata, Japan

Correspondence to Nobumasa Ohara, MD, Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, 1-754 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan. Tel: +81 25 368 9024; fax: +81 25 368 9024; e-mail:

Abbreviations: A2, α2-macroglobulin; BP, blood pressure; CRL, ceruloplasmin; eGFR, estimated glomerular filtration rate; IgG, immunoglobulin G; NAG, N-acetylglucosaminidase; pIs, isoelectric points; Tf, transferrin

Received 2 March, 2013

Revised 28 June, 2013

Accepted 9 September, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins