Dataset Information

The Urinary Angiotensinogen to Urinary Albumin Ratio Reflects Whether the Renin-angiotensin System in the Kidney Is Activated due to Filtration of Plasma Angiotensinogen through the Damaged Glomeruli or the Production of Angiotensinogen in the Proximal Tubules.

ABSTRACT: Objective Urinary angiotensinogen (AGT) is a surrogate marker for intrarenal renin-angiotensin system (RAS) activity that plays an important role in the development of renal damage. Urinary AGT levels are determined by the filtration of plasma AGT through the damaged glomeruli and production of AGT in the proximal tubules. However, the relative merits of the filtration and production of urinary AGT levels in chronic kidney diseases (CKD) have not been clarified. Therefore, we investigated them in CKD patients. Methods We recruited 41 biopsy-proven patients diagnosed with IgA nephropathy (IgAN) in 31, membranous nephropathy (MN) in 5, and tubulointerstitial nephritis (TIN) in 5. The patients taking RAS blockers were excluded. Results The urinary albumin levels in MN patients were significantly higher and those in TIN patients significantly lower than in IgAN patients, and the urinary AGT levels in the MN and TIN patients were significantly higher than those in IgAN patients. Conversely, the urinary AGT-to-urinary albumin (urinary AGT/Alb) ratios were the same for IgAN and MN patients, and those of TIN patients were significantly higher than those of IgAN and MN patients. A multiple linear regression analysis revealed that the urinary AGT/Alb ratios had a significant positive association with IgAN and TIN after adjustments (?=0.75, and p<0.01). Conclusion These data suggest that the origins of urinary AGT may differ according to the etiology of renal damage [i.e. glomerular damage (such as IgAN and MN) or tubulointerstitial damage (such as TIN)], and a higher urinary AGT/Alb ratio, as in TIN, may reflect AGT production in the kidney.

SUBMITTER: Ohashi N

PROVIDER: S-EPMC7028426 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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The Urinary Angiotensinogen to Urinary Albumin Ratio Reflects Whether the Renin-angiotensin System in the Kidney Is Activated due to Filtration of Plasma Angiotensinogen through the Damaged Glomeruli or the Production of Angiotensinogen in the Proximal Tubules.

Ohashi Naro N Aoki Taro T Matsuyama Takashi T Ishigaki Sayaka S Isobe Shinsuke S Katahashi Naoko N Sato Taichi T Fujikura Tomoyuki T Kato Akihiko A Yasuda Hideo H

Internal medicine (Tokyo, Japan) 20190918 3

Objective Urinary angiotensinogen (AGT) is a surrogate marker for intrarenal renin-angiotensin system (RAS) activity that plays an important role in the development of renal damage. Urinary AGT levels are determined by the filtration of plasma AGT through the damaged glomeruli and production of AGT in the proximal tubules. However, the relative merits of the filtration and production of urinary AGT levels in chronic kidney diseases (CKD) have not been clarified. Therefore, we investigated them i ...[more]

PMID: 31534091

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Project description:We reported previously that urinary angiotensinogen (UAGT) levels provide a specific index of the intrarenal renin-angiotensin system (RAS) status in angiotensin II-dependent hypertensive rats. To study this system in humans, we recently developed a human angiotensinogen ELISA. To test the hypothesis that UAGT is increased in hypertensive patients, we recruited 110 adults. Four subjects with estimated glomerular filtration levels <30 mL/min per 1.73 m(2) were excluded because previous studies have already shown that UAGT is highly correlated with estimated glomerular filtration in this stage of chronic kidney disease. Consequently, 106 paired samples of urine and plasma were analyzed from 70 hypertensive patients (39 treated with RAS blockers [angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers; systolic blood pressure: 139+/-3 mm Hg] and 31 not treated with RAS blockers [systolic blood pressure: 151+/-4 mm Hg]) and 36 normotensive subjects (systolic blood pressure: 122+/-2 mm Hg). UAGT, normalized by urinary concentrations of creatinine, were not correlated with race, gender, age, height, body weight, body mass index, fractional excretion of sodium, plasma angiotensinogen levels, or estimated glomerular filtration. However, UAGT/urinary concentration of creatinine was significantly positively correlated with systolic blood pressure, diastolic blood pressure, urinary albumin:creatinine ratio (r=0.5994), and urinary protein:creatinine ratio (r=0.4597). UAGT/urinary concentration of creatinine was significantly greater in hypertensive patients not treated with RAS blockers (25.00+/-4.96 microg/g) compared with normotensive subjects (13.70+/-2.33 microg/g). Importantly, patients treated with RAS blockers exhibited a marked attenuation of this augmentation (13.26+/-2.60 microg/g). These data indicate that UAGT is increased in hypertensive patients, and treatment with RAS blockers suppresses UAGT, suggesting that the efficacy of RAS blockade to reduce the intrarenal RAS activity can be assessed by measurements of UAGT.

Dataset Information

The Urinary Angiotensinogen to Urinary Albumin Ratio Reflects Whether the Renin-angiotensin System in the Kidney Is Activated due to Filtration of Plasma Angiotensinogen through the Damaged Glomeruli or the Production of Angiotensinogen in the Proximal Tubules.

Publications

The Urinary Angiotensinogen to Urinary Albumin Ratio Reflects Whether the Renin-angiotensin System in the Kidney Is Activated due to Filtration of Plasma Angiotensinogen through the Damaged Glomeruli or the Production of Angiotensinogen in the Proximal Tubules.

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