Skip to main content
Top
Published in: BMC Nephrology 1/2018

Open Access 01-12-2018 | Research article

The elevated levels of urinary angiotensinogen are correlated with the severity of idiopathic membranous nephropathy

Authors: Ziyong Tang, Yue Wang, Liyuan Tao, Yanhong Guo, Yimu Zheng, Danxia Zheng

Published in: BMC Nephrology | Issue 1/2018

Login to get access

Abstract

Background

Immunosuppressive treatment will predispose an idiopathic membranous nephropathy (iMN) patient to opportunistic infections. Disease severity is one of the main concerns for making the treatment decision. Urinary angiotensinogen (UAGT) level has been shown highly correlated with intrarenal renin-angiotensin system (RAS) activity and severity of chronic kidney diseases (CKD). We aimed to test the relationship between the UAGT level and the severity of iMN.

Methods

This cross-sectional study included a total of 48 biopsy-proven iMN patients, 46 minimal change disease (MCD) patients, and 44 healthy volunteers. The clinical and laboratory data and urine samples were collected from all subjects before the use of RAS inhibitors. We determined the UAGT levels with a method of enzyme-linked immunosorbent assay.

Results

The UAGT levels were not different between the iMN (277.05 ± 61.25, μg/g.Cr) and MCD patients (244.19 ± 40.24, μg/g.Cr), but both of them were significantly higher than those of healthy controls (6.85 ± 1.10, μg/g.Cr). UAGT levels were correlated negatively with serum albumin (r = − 0.393, p = 0.006) and estimated glomerular filtration rate (eGFR) (r = − 0.352, p = 0.014) and positively with 24-h proteinuria (r = 0.614, p < 0.001) in iMN patients but not in MCD patients. Multivariate linear regression analysis revealed that only proteinuria independently determinate the levels of UAGT (β = 0.649, p < 0.001) in iMN patients.

Conclusions

UAGT levels were correlated negatively with serum albumin and glomerular filtration rate and positively with proteinuria in iMN patients at the onset. This suggests that elevated levels of UAGT are associated with the severity of iMN. The UAGT level may be used as a cofactor for deciding immunosuppressive therapy in iMN patient.
Literature
1.
go back to reference Hou JH, Zhu HX, Zhou ML, Le WB, Zeng CH, Liang SS, et al. Changes in the Spectrum of kidney diseases: an analysis of 40,759 biopsy-proven cases from 2003 to 2014 in China. Kidney Dis (Basel). 2018;4(1):10–9.CrossRef Hou JH, Zhu HX, Zhou ML, Le WB, Zeng CH, Liang SS, et al. Changes in the Spectrum of kidney diseases: an analysis of 40,759 biopsy-proven cases from 2003 to 2014 in China. Kidney Dis (Basel). 2018;4(1):10–9.CrossRef
2.
go back to reference van den Brand JA, Hofstra JM, Wetzels JF. Low-molecular-weight proteins as prognostic markers in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2011;6(12):2846–53.CrossRef van den Brand JA, Hofstra JM, Wetzels JF. Low-molecular-weight proteins as prognostic markers in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2011;6(12):2846–53.CrossRef
3.
go back to reference van den Brand JA, van Dijk PR, Hofstra JM, Wetzels JF. Long-term outcomes in idiopathic membranous nephropathy using a restrictive treatment strategy. J Am Soc Nephrol. 2014;25(1):150–8.CrossRef van den Brand JA, van Dijk PR, Hofstra JM, Wetzels JF. Long-term outcomes in idiopathic membranous nephropathy using a restrictive treatment strategy. J Am Soc Nephrol. 2014;25(1):150–8.CrossRef
4.
go back to reference KDIGO. Kidney Disease: Improving global outcomes (KDIGO) glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney inter. Suppl. 2012;2:139–274.CrossRef KDIGO. Kidney Disease: Improving global outcomes (KDIGO) glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney inter. Suppl. 2012;2:139–274.CrossRef
5.
go back to reference Cattran DC, Pei Y, Greenwood CM, Ponticelli C, Passerini P, Honkanen E. Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications. Kidney Int. 1997;51(3):901–7.CrossRef Cattran DC, Pei Y, Greenwood CM, Ponticelli C, Passerini P, Honkanen E. Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications. Kidney Int. 1997;51(3):901–7.CrossRef
6.
go back to reference Bazzi C, Petrini C, Rizza V, Arrigo G, Napodano P, Paparella M, et al. Urinary N-acetyl-beta-glucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis. Nephrol Dial Transplant. 2002;17(11):1890–6.CrossRef Bazzi C, Petrini C, Rizza V, Arrigo G, Napodano P, Paparella M, et al. Urinary N-acetyl-beta-glucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis. Nephrol Dial Transplant. 2002;17(11):1890–6.CrossRef
7.
go back to reference Honkanen E, Teppo AM, Tornroth T, Groop PH, Gronhagen-Riska C. Urinary transforming growth factor-beta 1 in membranous glomerulonephritis. Nephrol Dial Transplant. 1997;12(12):2562–8.CrossRef Honkanen E, Teppo AM, Tornroth T, Groop PH, Gronhagen-Riska C. Urinary transforming growth factor-beta 1 in membranous glomerulonephritis. Nephrol Dial Transplant. 1997;12(12):2562–8.CrossRef
8.
go back to reference Ruiz-Ortega M, Egido J. Angiotensin II modulates cell growth-related events and synthesis of matrix proteins in renal interstitial fibroblasts. Kidney Int. 1997;52(6):1497–510.CrossRef Ruiz-Ortega M, Egido J. Angiotensin II modulates cell growth-related events and synthesis of matrix proteins in renal interstitial fibroblasts. Kidney Int. 1997;52(6):1497–510.CrossRef
9.
go back to reference Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007;59(3):251–87.CrossRef Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007;59(3):251–87.CrossRef
10.
go back to reference Lu H, Cassis LA, Kooi CW, Daugherty A. Structure and functions of angiotensinogen. Hypertens Res. 2016;39(7):492–500.CrossRef Lu H, Cassis LA, Kooi CW, Daugherty A. Structure and functions of angiotensinogen. Hypertens Res. 2016;39(7):492–500.CrossRef
11.
go back to reference Urushihara M, Kondo S, Kagami S, Kobori H. Urinary angiotensinogen accurately reflects intrarenal renin-angiotensin system activity. Am J Nephrol. 2010;31(4):318–25.CrossRef Urushihara M, Kondo S, Kagami S, Kobori H. Urinary angiotensinogen accurately reflects intrarenal renin-angiotensin system activity. Am J Nephrol. 2010;31(4):318–25.CrossRef
12.
go back to reference Takamatsu M, Urushihara M, Kondo S, Shimizu M, Morioka T, Oite T, et al. Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy. Pediatr Nephrol. 2008;23(8):1257–67.CrossRef Takamatsu M, Urushihara M, Kondo S, Shimizu M, Morioka T, Oite T, et al. Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy. Pediatr Nephrol. 2008;23(8):1257–67.CrossRef
13.
go back to reference Saito T, Urushihara M, Kotani Y, Kagami S, Kobori H. Increased urinary angiotensinogen is precedent to increased urinary albumin in patients with type 1 diabetes. Am J Med Sci. 2009;338(6):478–80.CrossRef Saito T, Urushihara M, Kotani Y, Kagami S, Kobori H. Increased urinary angiotensinogen is precedent to increased urinary albumin in patients with type 1 diabetes. Am J Med Sci. 2009;338(6):478–80.CrossRef
14.
go back to reference Satirapoj B, Siritaweesuk N, Supasyndh O. Urinary angiotensinogen as a potential biomarker of diabetic nephropathy. Clin Kidney J. 2014;7(4):354–60.CrossRef Satirapoj B, Siritaweesuk N, Supasyndh O. Urinary angiotensinogen as a potential biomarker of diabetic nephropathy. Clin Kidney J. 2014;7(4):354–60.CrossRef
15.
go back to reference Kim YG, Song SB, Lee SH, Moon JY, Jeong KH, Lee TW, et al. Urinary angiotensinogen as a predictive marker in patients with immunoglobulin a nephropathy. Clin Exp Nephrol. 2011;15(5):720–6.CrossRef Kim YG, Song SB, Lee SH, Moon JY, Jeong KH, Lee TW, et al. Urinary angiotensinogen as a predictive marker in patients with immunoglobulin a nephropathy. Clin Exp Nephrol. 2011;15(5):720–6.CrossRef
16.
go back to reference Nishiyama A, Konishi Y, Ohashi N, Morikawa T, Urushihara M, Maeda I, et al. Urinary angiotensinogen reflects the activity of intrarenal renin-angiotensin system in patients with IgA nephropathy. Nephrol Dial Transplant. 2011;26(1):170–7.CrossRef Nishiyama A, Konishi Y, Ohashi N, Morikawa T, Urushihara M, Maeda I, et al. Urinary angiotensinogen reflects the activity of intrarenal renin-angiotensin system in patients with IgA nephropathy. Nephrol Dial Transplant. 2011;26(1):170–7.CrossRef
17.
go back to reference Mezzano SA, Aros CA, Droguett A, Burgos ME, Ardiles LG, Flores CA, et al. Renal angiotensin II up-regulation and myofibroblast activation in human membranous nephropathy. Kidney Int. 2003;64(s86):S39–45. Mezzano SA, Aros CA, Droguett A, Burgos ME, Ardiles LG, Flores CA, et al. Renal angiotensin II up-regulation and myofibroblast activation in human membranous nephropathy. Kidney Int. 2003;64(s86):S39–45.
18.
go back to reference Tang Z, Cheng LT, Li HY, Wang T. Serum uric acid and endothelial dysfunction in continuous ambulatory peritoneal dialysis patients. Am J Nephrol. 2009;29(5):368–73.CrossRef Tang Z, Cheng LT, Li HY, Wang T. Serum uric acid and endothelial dysfunction in continuous ambulatory peritoneal dialysis patients. Am J Nephrol. 2009;29(5):368–73.CrossRef
19.
go back to reference Cattran DC, Feehally J, Terence Cook H, et al. Kidney Disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and Management of Chronic Kidney Disease. Kidney inter.Suppl. 2013;3:1–150.CrossRef Cattran DC, Feehally J, Terence Cook H, et al. Kidney Disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and Management of Chronic Kidney Disease. Kidney inter.Suppl. 2013;3:1–150.CrossRef
20.
go back to reference van den Brand JA, van Dijk PR, Hofstra JM, Wetzels JF. Cancer risk after cyclophosphamide treatment in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2014;9(6):1066–73.CrossRef van den Brand JA, van Dijk PR, Hofstra JM, Wetzels JF. Cancer risk after cyclophosphamide treatment in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2014;9(6):1066–73.CrossRef
21.
go back to reference van den Brand JA, Hofstra JM, Wetzels JF. Prognostic value of risk score and urinary markers in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2012;7(8):1242–8.CrossRef van den Brand JA, Hofstra JM, Wetzels JF. Prognostic value of risk score and urinary markers in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2012;7(8):1242–8.CrossRef
22.
go back to reference Huh H, Lee H, Lee JP, Kim DK, Oh S, Oh YK, et al. Factors affecting the long-term outcomes of idiopathic membranous nephropathy. BMC Nephrol. 2017;18(1):104.CrossRef Huh H, Lee H, Lee JP, Kim DK, Oh S, Oh YK, et al. Factors affecting the long-term outcomes of idiopathic membranous nephropathy. BMC Nephrol. 2017;18(1):104.CrossRef
23.
go back to reference Gupta S, Connolly J, Pepper RJ, Walsh SB, Yaqoob MM, Kleta R, et al. Membranous nephropathy: a retrospective observational study of membranous nephropathy in north east and Central London. BMC Nephrol. 2017;18(1):201.CrossRef Gupta S, Connolly J, Pepper RJ, Walsh SB, Yaqoob MM, Kleta R, et al. Membranous nephropathy: a retrospective observational study of membranous nephropathy in north east and Central London. BMC Nephrol. 2017;18(1):201.CrossRef
24.
go back to reference Kobori H, Ohashi N, Katsurada A, Miyata K, Satou R, Saito T, et al. Urinary angiotensinogen as a potential biomarker of severity of chronic kidney diseases. J Am Soc Hypertens. 2008;2(5):349–54.CrossRef Kobori H, Ohashi N, Katsurada A, Miyata K, Satou R, Saito T, et al. Urinary angiotensinogen as a potential biomarker of severity of chronic kidney diseases. J Am Soc Hypertens. 2008;2(5):349–54.CrossRef
25.
go back to reference Jang HR, Jeon J, Park JH, Lee JE, Huh W, Oh HY, et al. Clinical relevance of urinary angiotensinogen and renin as potential biomarkers in patients with overt proteinuria. Transl Res. 2014;164(5):400–10.CrossRef Jang HR, Jeon J, Park JH, Lee JE, Huh W, Oh HY, et al. Clinical relevance of urinary angiotensinogen and renin as potential biomarkers in patients with overt proteinuria. Transl Res. 2014;164(5):400–10.CrossRef
26.
go back to reference Yamamoto T, Nakagawa T, Suzuki H, Ohashi N, Fukasawa H, Fujigaki Y, et al. 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. 2007;18(5):1558–65.CrossRef Yamamoto T, Nakagawa T, Suzuki H, Ohashi N, Fukasawa H, Fujigaki Y, et al. 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. 2007;18(5):1558–65.CrossRef
27.
go back to reference Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11–21.CrossRef Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11–21.CrossRef
28.
go back to reference Bertelli R, Bonanni A, Di Donato A, Cioni M, Ravani P, Ghiggeri GM. Regulatory T cells and minimal change nephropathy: in the midst of a complex network. Clin Exp Immunol. 2016;183(2):166–74.CrossRef Bertelli R, Bonanni A, Di Donato A, Cioni M, Ravani P, Ghiggeri GM. Regulatory T cells and minimal change nephropathy: in the midst of a complex network. Clin Exp Immunol. 2016;183(2):166–74.CrossRef
29.
go back to reference Liu LL, Qin Y, Cai JF, Wang HY, Tao JL, Li H, et al. Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome. Clin Immunol. 2011;139(3):314–20.CrossRef Liu LL, Qin Y, Cai JF, Wang HY, Tao JL, Li H, et al. Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome. Clin Immunol. 2011;139(3):314–20.CrossRef
30.
go back to reference Hashimura Y, Nozu K, Kanegane H, Miyawaki T, Hayakawa A, Yoshikawa N, et al. Minimal change nephrotic syndrome associated with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Pediatr Nephrol. 2009;24(6):1181–6.CrossRef Hashimura Y, Nozu K, Kanegane H, Miyawaki T, Hayakawa A, Yoshikawa N, et al. Minimal change nephrotic syndrome associated with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Pediatr Nephrol. 2009;24(6):1181–6.CrossRef
Metadata
Title
The elevated levels of urinary angiotensinogen are correlated with the severity of idiopathic membranous nephropathy
Authors
Ziyong Tang
Yue Wang
Liyuan Tao
Yanhong Guo
Yimu Zheng
Danxia Zheng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2018
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-018-1165-1

Other articles of this Issue 1/2018

BMC Nephrology 1/2018 Go to the issue