Poor glycemic control and decreased renal function are associated with increased intrarenal RAS activity in Type 2 diabetes mellitus.
OBJECTIVE
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.
Departments of Metabolism, Endocrinology, and Molecular Medicine Osaka City University Graduate School of Medicine, Osaka, Japan; Departments of Nephrology, Osaka City University Graduate School of Medicine, Osaka, Japan.
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Nakatani
Departments of Nephrology, Osaka City University Graduate School of Medicine, Osaka, Japan. Electronic address: ish@med.osaka-cu.ac.jp.
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Ishimura
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
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Naganuma
Departments of Metabolism, Endocrinology, and Molecular Medicine Osaka City University Graduate School of Medicine, Osaka, Japan.
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Nakatani
Departments of Metabolism, Endocrinology, and Molecular Medicine Osaka City University Graduate School of Medicine, Osaka, Japan; Departments of Nephrology, Osaka City University Graduate School of Medicine, Osaka, Japan.
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Ichii
Departments of Metabolism, Endocrinology, and Molecular Medicine Osaka City University Graduate School of Medicine, Osaka, Japan.
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Fukumoto
Departments of Metabolism, Endocrinology, and Molecular Medicine Osaka City University Graduate School of Medicine, Osaka, Japan.
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Mori
Departments of Metabolism, Endocrinology, and Molecular Medicine Osaka City University Graduate School of Medicine, Osaka, Japan.
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Emoto
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
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Nakatani
Departments of Metabolism, Endocrinology, and Molecular Medicine Osaka City University Graduate School of Medicine, Osaka, Japan.
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Inaba
D000368:Aged; D000808:Angiotensinogen / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology* / Q000652:urine; D012084:Renin-Angiotensin System / Q000502:physiology*
D000808:Angiotensinogen; D015415:Biomarkers; D001786:Blood Glucose; D003404:Creatinine; D006442:Glycated Hemoglobin
Diabetic nephropathy; Renin–angiotensin system; Type 2 diabetes mellitus; Urinary angiotensinogen