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Proximal tubular angiotensinogen in renal biopsy suggests nondipper BP rhythm accompanied by enhanced tubular sodium reabsorption

Fukuda, Michioa; Urushihara, Makib; Wakamatsu, Tamakia; Oikawa, Tadashia; Kobori, Hiroyukib

doi: 10.1097/HJH.0b013e328353e807
ORIGINAL PAPERS: Kidney
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Objectives: The renal capacity for sodium excretion is impaired by a reduction in the glomerular ultrafiltration coefficient and by enhancement of the fractional tubular sodium reabsorption (FRNa), leading to a nondipper circadian blood pressure (BP) rhythm. Angiotensin II in the systemic circulation can be easily filtered across the glomerular capillary walls and stimulates renal proximal tubular angiotensinogen (PT-AGT) production, leading to the activation of intrarenal angiotensin II, which is known to augment the FRNa in animal models.

Methods: We performed an immunohistochemical investigation to determine the contribution of PT-AGT to enhancement of FRNa and the nondipper circadian BP rhythm in 40 consecutive patients with primary IgA nephropathy (IgAN).

Results: Immunostaining for PT-AGT was increased in the IgAN patients compared with control individuals (P = 0.04), and correlated directly with the FRNa (r = 0.39, P = 0.01) and the night/day ratio of BP (r = 0.38, P = 0.02), but not creatinine clearance (r = −0.008, P = 0.9). The night/day ratio of BP was determined by both creatinine clearance (r = −0.36, P = 0.03) and FRNa (r = 0.47, P = 0.006).

Conclusion: Tubular sodium reabsorption is stimulated by intrarenal angiotensin II, as indicated by PT-AGT, and contributes to the genesis of the nondipper BP rhythm. Further studies are needed to evaluate whether or not treatment to prevent sodium retention is useful for patients who exhibit increased PT-AGT in renal biopsies.

aDepartment of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

bDepartment of Physiology, and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana, USA

Correspondence to Michio Fukuda, MD, PhD, Associate Professor, Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, 467–8601 Nagoya, Japan.Tel: +81 52 853 8221; fax: +81 52 852 3796; e-mail: m-fukuda@med.nagoya-cu.ac.jp

Abbreviations: AGT, angiotensinogen; Ang, angiotensin; ARB, angiotensin II type 1 receptor blocker; AT1R, angiotensin II type 1 receptor; BP, blood pressure; Ccr, creatinine clearance; CKD, chronic kidney disease; FRNa, fractional tubular sodium reabsorption; GFR, glomerular filtration rate; IgAN, IgA nephropathy; KF, glomerular ultrafiltration coefficient; Km, Michaelis-Menten constant; MAP, mean arterial pressure; PAC, plasma aldosterone concentration; PRA, plasma renin activity; PT-AGT, proximal tubular angiotensinogen; SNa, plasma sodium concentration; tNa, tubular sodium reabsorption; UNaV, urinary sodium excretion

Received 23 October, 2011

Revised 11 February, 2012

Accepted 20 March, 2012

© 2012 Lippincott Williams & Wilkins, Inc.