Top

Pediatric Nephrology

Published in:

Open Access 01-07-2013 | Original Article

Urinary angiotensinogen as a marker of intrarenal angiotensin II activity in adolescents with primary hypertension

Authors: Elżbieta Kuroczycka-Saniutycz, Anna Wasilewska, Agnieszka Sulik, Robert Milewski

Published in: Pediatric Nephrology | Issue 7/2013

Abstract

Background

Experimental and epidemiological studies have demonstrated that urinary angiotensinogen (AGT) is a novel biomarker for the intrarenal activity of the renin–angiotensin system in hypertension (HT). Several large-scale epidemiological studies have shown that an elevated serum uric acid (SUA) level is associated with HT. The aim of our study was to assess urinary AGT excretion and its correlation with SUA level, the lipid profile, and the body mass index (BMI) Z-score in hypertensive adolescents.

Methods

Participants were divided into two groups: (1) the group with confirmed HT consisting of 55 subjects with primary HT and (2) the reference (R) group consisting of 33 subjects with white-coat HT. A commercial enzyme-linked immunosorbent assay (ELISA) kit was used to determine urinary AGT concentration.

Results

The urinary AGT/creatinine (cr.) ratio in subjects in the HT group was significantly higher than that in the reference group (p < 0.01) and showed a strong positive correlation with SUA (r = 0.47, p < 0.01). The relationship between the AGT/cr. ratio and SUA levels after controlling for age, gender and BMI Z-score continued to show a significant association.

Conclusions

The most obvious finding to emerge from this study is that in adolescents with primary HT, the increased urinary excretion of AGT correlated with hyperuricemia, although large, multicenter studies are needed to confirm this observation.

Masuo K, Kawaguchi H, Mikami H, Ogihara T, Tuck ML (2003) Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 42:474–480PubMedCrossRef

Sundström J, Sullivan L, D’Agostino RB, Levy D, Kannel WB, Vasan RS (2005) Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 45:28–33PubMed

Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ (2001) Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 38:1101–1106PubMedCrossRef

Perlstein TS, Gumieniak O, Williams GH, Sparrow D, Vokonas PS, Gaziano M, Weiss ST, Litonjua AA (2006) Uric acid and the development of hypertension: the normative aging study. Hypertension 48:1031–1036PubMedCrossRef

Feig DI, Johnson RJ (2003) Hyperuricemia in childhood primary hypertension. Hypertension 42:247–252PubMedCrossRef

Saito I, Saruta T, Kondo K, Nakamura R, Oguro T, Yamagami K, Ozawa Y, Kato E (1978) Serum uric acid and the renin–angiotensin system in hypertension. J Am Geriatr Soc 26:241–247PubMed

Dzau VJ, Re R (1994) Tissue angiotensin system in cardiovascular medicine. A paradigm shift? Circulation 89:493–498PubMedCrossRef

Baltatu O, Silva JA Jr, Ganten D, Bader M (2000) The brain renin–angiotensin system modulates angiotensin II-induced hypertension and cardiac hypertrophy. Hypertension 35:409–412PubMedCrossRef

Dell’Italia LJ, Meng QC, Balcells E, Wei CC, Palmer R, Hageman GR, Durand J, Hankes GH, Oparil S (1997) Compartmentalization of angiotensin II generation in the dog heart evidence for independent mechanisms in intravascular and interstitial spaces. J Clin Invest 100:253–258PubMedCrossRef

10.

Mazzocchi G, Malendowicz LK, Markowska A, Albertin G, Nussdorfer GG (2000) Role of adrenal renin–angiotensin system in the control of aldosterone secretion in sodium-restricted rats. Am J Physiol Endocrinol Metab 278:E1027–E1030PubMed

11.

Danser AH, Admiraal PJ, Derkx FH, Schalekamp MA (1998) Angiotensin I-to-II conversion in the human renal vascular bed. J Hypertens 16:2051–2056PubMedCrossRef

12.

Navar LG, Harrison-Bernard LM, Nishiyama A, Kobori H (2002) Regulation of intrarenal angiotensin II in hypertension. Hypertension 39:316–322PubMedCrossRef

13.

Kobori H, Nangaku M, Navar LG, Nishiyama A (2007) The intrarenal renin–angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 59:251–287PubMedCrossRef

14.

Kobori H, Ozawa Y, Suzaki Y, Prieto-Carrasquero MC, Nishiyama A, Shoji T, Cohen EP, Navar LG (2006) Young Scholars Award Lecture: intratubular angiotensinogen in hypertension and kidney diseases. Am J Hypertens 19:541–550PubMedCrossRef

15.

Kobori H, Ozawa Y, Satou R, Katsurada A, Miyata K, Ohashi N, Hase N, Suzaki Y, Sigmund CD, Navar LG (2007) Kidney-specific enhancement of ANG II stimulates endogenous intrarenal angiotensinogen in gene-targeted mice. Am J Physiol Renal Physiol 293:F938–F945PubMedCrossRef

16.

Katsurada A, Hagiwara Y, Miyashita K, Satou R, Miyata K, Ohashi N, Navar LG, Kobori H (2007) Novel sandwich ELISA for human angiotensinogen. Am J Physiol Renal Physiol 293:F956–F960PubMedCrossRef

17.

Kobori H, Harrison-Bernard LM, Navar LG (2002) Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production. Kidney Int 61:579–585PubMedCrossRef

18.

Kobori H, Nishiyama A, Harrison-Bernard LM, Navar LG (2003) Urinary angiotensinogen as an indicator of intrarenal Angiotensin status in hypertension. Hypertension 41:42–49PubMedCrossRef

19.

Kobori H, Alper AB Jr, Shenava R, Katsurada A, Saito T, Ohashi N, Urushihara M, Miyata K, Satou R, Hamm LL, Navar LG (2009) Urinary angiotensinogen as a novel biomarker of the intrarenal renin-angiotensin system status in hypertensive patients. Hypertension 53:344–350PubMedCrossRef

20.

Urbina E, Alpert B, Flynn J, Hayman L, Harshfield GA, Jacobson M, Mahoney L, McCrindle B, Mietus-Snyder M, Steinberger J, Daniels S, American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee (2008) Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension 52:433–451PubMedCrossRef

21.

Wühl E, Witte K, Soergel M, Mehls O, Schaefer F, German Working Group on Pediatric Hypertension (2002) Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions. J Hypertens 20:1995–2007PubMedCrossRef

22.

Yoon EY, Cohn L, Rocchini A, Kershaw D, Freed G, Ascione F, Clark S (2012) Antihypertensive prescribing patterns for adolescents with primary hypertension. Pediatrics 129:e1–e8PubMedCrossRef

23.

Feig DI, Kang DH, Johnson RJ (2008) Uric acid and cardiovascular risk. N Engl J Med 359:1811–1821PubMedCrossRef

24.

Feig DI, Kang DH, Nakagawa T, Mazzali M, Johnson RJ (2006) Uric acid and hypertension. Curr Hypertens Rep 8:111–115PubMedCrossRef

25.

Mellen PB, Bleyer AJ, Erlinger TP, Evans GW, Nieto FJ, Wagenknecht LE, Wofford MR, Herrington DM (2006) Serum uric acid predicts incident hypertension in a biethnic cohort. Hypertension 48:1037–1042PubMedCrossRef

26.

Selby JV, Friedman GD, Quesenberry CP (1990) Precursors of essential hypertension: pulmonary function, heart rate, uric acid, serum cholesterol, and other serum chemistries. Am J Epidemiol 131:1017–1027PubMed

27.

Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M (2003) Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41:1183–1190PubMedCrossRef

28.

Leyva F, Anker SD, Godsland IF, Teixeira M, Hellewell PG, Kox WJ, Poole-Wilson PA, Coats AJ (1998) Uric acid in chronic heart failure: a marker of chronic inflammation. Eur Heart J 19:1814–1822PubMedCrossRef

29.

Loeffler LF, Navas-Acien A, Brady TM, Miller ER 3rd, Fadrowski JJ (2012) Uric acid level and elevated blood pressure in US adolescents: National Health and Nutrition Examination Survey, 1999–2006. Hypertension 59:811–817PubMedCrossRef

30.

Corry DB, Eslami P, Yamamoto K, Nyby MD, Makino H, Tuck ML (2008) Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens 26:269–275PubMedCrossRef

31.

Navar LG, Harrison-Bernard LM, Wang CT, Cervenka L, Mitchell KD (1999) Concentrations and actions of intraluminal angiotensin II. J Am Soc Nephrol 10:S189–S195PubMed

32.

Seikaly MG, Arant BS Jr, Seney FD Jr (1990) Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest 86:1352–1357PubMedCrossRef

33.

Navar LG, Imig JD, Zou L, Wang CT (1997) Intrarenal production of angiotensin II. Semin Nephrol 17:412–422PubMed

34.

van den Heuvel M, Batenburg WW, Jainandunsing S, Garrelds IM, van Gool JM, Feelders RA, van den Meiracker AH, Danser AH (2011) Urinary renin, but not angiotensinogen or aldosterone, reflects the renal renin-angiotensin-aldosterone system activity and the efficacy of renin-angiotensin-aldosterone system blockade in the kidney. J Hypertens 29:2147–2155PubMedCrossRef

35.

Yamamoto T, Nakagawa T, Suzuki H, Ohashi N, Fukasawa H, Fujigaki Y, Kato A, Nakamura Y, Suzuki F, Hishida A (2007) Urinary angiotensinogen as a marker of intrarenal angiotensin II activity associated with deterioration of renal function in patients with chronic kidney disease. J Am Soc Nephrol 18:1558–1565PubMedCrossRef

36.

Kobori H, Ohashi N, Katsurada A, Miyata K, Satou R, Saito T, Yamamoto T (2008) Urinary angiotensinogen as a potential biomarker of severity of chronic kidney diseases. J Am Soc Hypertens 2:349–354PubMedCrossRef

37.

Mezzano S, Droguett A, Burgos ME, Ardiles LG, Flores CA, Aros CA, Caorsi I, Vio CP, Ruiz-Ortega M, Egido J (2003) Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney Int 64:S64–S70CrossRef

38.

Mezzano SA, Aros CA, Droguett A, Burgos ME, Ardiles LG, Flores CA, Carpio D, Vio CP, Ruiz-Ortega M, Egido J (2003) Renal angiotensin II up-regulation and myofibroblast activation in human membranous nephropathy. Kidney Int 64:S39–S45CrossRef

39.

Lantelme P, Rohrwasser A, Vincent M, Cheng T, Gardier S, Legedz L, Bricca G, Lalouel JM, Milon H (2005) Significance of urinary angiotensinogen in essential hypertension as a function of plasma renin and aldosterone status. J Hypertens 23:785–792PubMedCrossRef

Title: Urinary angiotensinogen as a marker of intrarenal angiotensin II activity in adolescents with primary hypertension
Authors: Elżbieta Kuroczycka-Saniutycz
Anna Wasilewska
Agnieszka Sulik
Robert Milewski
Publication date: 01-07-2013
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 7/2013
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-013-2449-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Urinary angiotensinogen as a marker of intrarenal angiotensin II activity in adolescents with primary hypertension

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 7/2013

Maximising living donation with paediatric blood-group-incompatible renal transplantation

Cystatin C adaptation in the first month of life

A rare cause of nephrotic syndrome in a 14-year-old boy: Questions

A rare cause of nephrotic syndrome in a 14-year-old boy: Answers

Epidemiology of cardiac surgery-associated acute kidney injury in neonates: a retrospective study

Indications for use and safety of rituximab in childhood renal diseases