Poor glycemic control and decreased renal function are associated with increased intrarenal RAS activity in Type 2 diabetes mellitus

• Published in: Diabetes research and clinical practice 2014-07, Vol.105 (1), p.40-46
• Main Authors: Nakatani, S, Ishimura, E, Naganuma, T, Nakatani, A, Ichii, M, Fukumoto, S, Mori, K, Emoto, M, Nakatani, T, Inaba, M
• Format: Article
• Language: English
• Subjects: Aged; Angiotensinogen - urine; Biomarkers - urine; Blood Glucose - metabolism; Case-Control Studies; Creatinine - urine; Diabetes Mellitus, Type 2 - physiopathology; Diabetes Mellitus, Type 2 - urine; Diabetic Nephropathies - physiopathology; Diabetic Nephropathies - urine; Diabetic nephropathy; Endocrinology & Metabolism; Female; Follow-Up Studies; Glomerular Filtration Rate - physiology; Glycated Hemoglobin A - analysis; Humans; Kidney Function Tests; Male; Middle Aged; Renal Insufficiency, Chronic - physiopathology; Renal Insufficiency, Chronic - urine; Renin-Angiotensin System - physiology; Renin–angiotensin system; Type 2 diabetes mellitus; Urinary angiotensinogen
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/j.diabres.2014.04.019

Abstract Aims The renin–angiotensin system (RAS) plays an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to investigate intrarenal RAS activity in patients with type 2 diabetes (T2DM). Methods We measured urinary angiotensinogen, a reliable biomarker of intrarenal RAS activity, in 14 controls without T2DM, 25 T2DM patients without nephropathy, 11 chronic kidney disease (CKD) patients without T2DM and 46 CKD patients with T2DM. Associations between urinary angiotensinogen and clinical parameters were examined. Results Compared with the controls, urinary [angiotensinogen:creatinine] were significantly higher in T2DM patients without nephropathy (4.70 ± 2.22 vs. 8.31 ± 5.27 μg/g, p = 0.037). Age, hemoglobin A1c (HbA1c) and fasting plasma glucose correlated significantly and positively with the log{urinary [angiotensinogen:creatinine]} ( r = 0.632, p = 0.007; r = 0.405, p = 0.027; r = 0.583, p = 0.003, respectively) in T2DM patients without nephropathy. In contrast, the urinary [angiotensinogen:creatinine] were not significantly different between CKD patients with and without T2DM (22.7 ± 27.8 vs. 33.5 ± 40.8 μg/g, p = 0.740); although they were significantly higher when compared with non-CKD patients. In the CKD patients with T2DM systolic blood pressure, serum creatinine, estimated glomerular filtration rate and urinary [albumin:creatinine] correlated significantly with the log{urinary [angiotensinogen:creatinine]} ( r = 0.412, p = 0.004; r = 0.308, p = 0.037; r = −0.382, p = 0.001; r = 0.648, p < 0.001, p < 0.001, respectively). Conclusions Our findings indicate that poor glycemic control is significantly associated with intrarenal RAS activity in T2DM patients without nephropathy, and that decreased renal function is significantly associated with intrarenal RAS activity in CKD patients with T2DM.