Skip to main content
SpringerLink
Log in

Activation of the aldosterone/mineralocorticoid receptor system in chronic kidney disease and metabolic syndrome

  • Review Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Recent clinical and experimental studies have shown that aldosterone is a potent inducer of proteinuria and that mineralocorticoid receptor (MR) antagonists confer efficient antiproteinuric effects. We identified glomerular epithelial cells (podocytes) as novel targets of aldosterone; activation of MR injures podocytes possibly via oxidative stress, resulting in disruption of glomerular filtration barrier, proteinuria, and progression of chronic kidney disease. We also demonstrated that SHR/cp, a rat model of metabolic syndrome, was susceptible to podocyte injury and proteinuria. Aldosterone excess caused by adipocyte-derived aldosterone-releasing factors was suggested to underlie the nephropathy. High salt intake augmented MR activation in the kidney and exacerbated the nephropathy. Furthermore, we identified an alternative pathway of MR activation by small GTPase Rac1. RhoGDIα knockout mice, a model with Rac1 activation in the kidney, showed albuminuria, podocyte injury, and glomerulosclerosis. Renal injury in the knockout mice was accompanied by enhanced MR signaling in the kidney despite normoaldosteronemia, and was ameliorated by an MR antagonist, eplerenone. Moreover, Rac-specific inhibitor significantly reduced the nephropathy, concomitantly with repression of MR activation. In vitro transfection studies provided direct evidence of Rac1-mediated MR activation. In conclusion, our findings suggest that MR activation plays a pivotal role in the pathogenesis of chronic kidney disease in metabolic syndrome, and that MR may be activated both aldosterone dependently (via aldosterone-releasing factors) and independently (via Rac1). MR antagonists are promising antiproteinuric drugs in metabolic syndrome, although long-term effects on renal outcomes, mortality, and safety need to be established.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Arriza JL, Weinberger C, Cerelli G, et al. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987;237:268–75.

    Article  CAS  PubMed  Google Scholar 

  2. Epstein M. Aldosterone blockade: an emerging strategy for abrogating progressive renal disease. Am J Med. 2006;119:912–9.

    Article  CAS  PubMed  Google Scholar 

  3. Hostetter TH, Ibrahim HN. Aldosterone in chronic kidney and cardiac disease. J Am Soc Nephrol. 2003;14:2395–401.

    Article  PubMed  Google Scholar 

  4. Weber KT. Aldosterone in congestive heart failure. N Engl J Med. 2001;345:1689–97.

    Article  CAS  PubMed  Google Scholar 

  5. Vasan RS, Evans JC, Larson MG, et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med. 2004;351:33–41.

    Article  CAS  PubMed  Google Scholar 

  6. Ingelsson E, Pencina MJ, Tofler GH, et al. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham Offspring Study. Circulation. 2007;116:984–92.

    Article  CAS  PubMed  Google Scholar 

  7. Guder G, Bauersachs J, Frantz S, et al. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure. Circulation. 2007;115:1754–61.

    Article  PubMed  Google Scholar 

  8. Beygui F, Collet JP, Benoliel JJ, et al. High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation. 2006;114:2604–10.

    Article  CAS  PubMed  Google Scholar 

  9. Hene RJ, Boer P, Koomans HA, Mees EJ. Plasma aldosterone concentrations in chronic renal disease. Kidney Int. 1982;21:98–101.

    Article  CAS  PubMed  Google Scholar 

  10. Quinkler M, Zehnder D, Eardley KS, et al. Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation. 2005;112:1435–43.

    Article  CAS  PubMed  Google Scholar 

  11. Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49:355–64.

    Article  CAS  PubMed  Google Scholar 

  12. Nagase M, Yoshida S, Shibata S, et al. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors. J Am Soc Nephrol. 2006;17:3438–46.

    Article  CAS  PubMed  Google Scholar 

  13. Shibata S, Nagase M, Yoshida S, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med. 2008;14:1370–6.

    Article  CAS  PubMed  Google Scholar 

  14. Selye H, Hall C. Pathologic changes induced in various species by overdosage with desoxycorticosterone. Arch Pathol. 1943;36:19–31.

    CAS  Google Scholar 

  15. Brilla CG, Pick R, Tan LB, Janicki JS, Weber KT. Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res. 1990;67:1355–64.

    CAS  PubMed  Google Scholar 

  16. Young M, Fullerton M, Dilley R, Funder J. Mineralocorticoids, hypertension, and cardiac fibrosis. J Clin Invest. 1994;93:2578–83.

    Article  CAS  PubMed  Google Scholar 

  17. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709–17.

    Article  CAS  PubMed  Google Scholar 

  18. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–21.

    Article  CAS  PubMed  Google Scholar 

  19. Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation. 2003;108:1831–8.

    Article  CAS  PubMed  Google Scholar 

  20. Williams GH, Burgess E, Kolloch RE, et al. Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol. 2004;93:990–6.

    Article  CAS  PubMed  Google Scholar 

  21. Funder JW, Pearce PT, Smith R, Smith AI. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science. 1988;242:583–5.

    Article  CAS  PubMed  Google Scholar 

  22. Kataoka S, Kudo A, Hirano H, et al. 11beta-hydroxysteroid dehydrogenase type 2 is expressed in the human kidney glomerulus. J Clin Endocrinol Metab. 2002;87:877–82.

    Article  CAS  PubMed  Google Scholar 

  23. Terada Y, Kobayashi T, Kuwana H, et al. Aldosterone stimulates proliferation of mesangial cells by activating mitogen-activated protein kinase 1/2, cyclin D1, and cyclin A. J Am Soc Nephrol. 2005;16:2296–305.

    Article  CAS  PubMed  Google Scholar 

  24. Gomez-Sanchez EP, Ganjam V, Chen YJ, et al. Regulation of 11 beta-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol. Am J Physiol Endocrinol Metab. 2003;285:E272–9.

    CAS  PubMed  Google Scholar 

  25. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329:1456–62.

    Article  CAS  PubMed  Google Scholar 

  26. Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med. 1996;334:939–45.

    Article  CAS  PubMed  Google Scholar 

  27. Jafar TH, Schmid CH, Landa M, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med. 2001;135:73–87.

    CAS  PubMed  Google Scholar 

  28. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–9.

    Article  CAS  PubMed  Google Scholar 

  29. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–60.

    Article  CAS  PubMed  Google Scholar 

  30. Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870–8.

    Article  CAS  PubMed  Google Scholar 

  31. Greene EL, Kren S, Hostetter TH. Role of aldosterone in the remnant kidney model in the rat. J Clin Invest. 1996;98:1063–8.

    Article  CAS  PubMed  Google Scholar 

  32. Quan ZY, Walser M, Hill GS. Adrenalectomy ameliorates ablative nephropathy in the rat independently of corticosterone maintenance level. Kidney Int. 1992;41:326–33.

    Article  CAS  PubMed  Google Scholar 

  33. Rocha R, Chander PN, Zuckerman A, Stier CT Jr. Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension. 1999;33:232–7.

    CAS  PubMed  Google Scholar 

  34. Chander PN, Rocha R, Ranaudo J, et al. Aldosterone plays a pivotal role in the pathogenesis of thrombotic microangiopathy in SHRSP. J Am Soc Nephrol. 2003;14:1990–7.

    Article  CAS  PubMed  Google Scholar 

  35. Horiuchi M, Nishiyama H, Hama J, et al. Characterization of renal aldosterone receptors in genetically hypertensive rats. Am J Physiol. 1993;264:F286–91.

    CAS  PubMed  Google Scholar 

  36. Lea WB, Kwak ES, Luther JM, et al. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt. Kidney Int. 2009;75:936–44.

    Article  CAS  PubMed  Google Scholar 

  37. Fiebeler A, Nussberger J, Shagdarsuren E, et al. Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage. Circulation. 2005;111:3087–94.

    Article  CAS  PubMed  Google Scholar 

  38. Blasi ER, Rocha R, Rudolph AE, et al. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int. 2003;63:1791–800.

    Article  CAS  PubMed  Google Scholar 

  39. Kretzler M, Koeppen-Hagemann I, Kriz W. Podocyte damage is a critical step in the development of glomerulosclerosis in the uninephrectomised-desoxycorticosterone hypertensive rat. Virchows Arch. 1994;425:181–93.

    Article  CAS  PubMed  Google Scholar 

  40. Artunc F, Amann K, Nasir O, et al. Blunted DOCA/high salt induced albuminuria and renal tubulointerstitial damage in gene-targeted mice lacking SGK1. J Mol Med. 2006;84:737–46.

    Article  CAS  PubMed  Google Scholar 

  41. Conn JW, Knopf RF, Nesbit RM. Clinical characteristics of primary aldosteronism from an analysis of 145 cases. Am J Surg. 1964;107:159–72.

    Article  CAS  PubMed  Google Scholar 

  42. Ribstein J, Du Cailar G, Fesler P, Mimran A. Relative glomerular hyperfiltration in primary aldosteronism. J Am Soc Nephrol. 2005;16:1320–5.

    Article  PubMed  Google Scholar 

  43. Rossi GP, Bernini G, Desideri G, et al. Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension. 2006;48:232–8.

    Article  CAS  PubMed  Google Scholar 

  44. Mehdi UF, Adams-Huet B, Raskin P, Vega GL, Toto RD. Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy. J Am Soc Nephrol. 2009;20:2641–50.

    Article  CAS  PubMed  Google Scholar 

  45. Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2009;4:542–51.

    Article  CAS  PubMed  Google Scholar 

  46. Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol. 2007;3:486–92.

    Article  CAS  PubMed  Google Scholar 

  47. Staessen J, Lijnen P, Fagard R, Verschueren LJ, Amery A. Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol. 1981;91:457–65.

    Article  CAS  PubMed  Google Scholar 

  48. Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41:64–8.

    Article  CAS  PubMed  Google Scholar 

  49. Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006;70:2116–23.

    CAS  PubMed  Google Scholar 

  50. Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006;354:1387–401.

    Article  CAS  PubMed  Google Scholar 

  51. Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003;83:253–307.

    CAS  PubMed  Google Scholar 

  52. Pagtalunan ME, Miller PL, Jumping-Eagle S, et al. Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest. 1997;99:342–8.

    Article  CAS  PubMed  Google Scholar 

  53. Wolf G, Chen S, Ziyadeh FN. From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Diabetes. 2005;54:1626–34.

    Article  CAS  PubMed  Google Scholar 

  54. Nagase M, Shibata S, Yoshida S, et al. Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. Hypertension. 2006;47:1084–93.

    Article  CAS  PubMed  Google Scholar 

  55. Chen HM, Liu ZH, Zeng CH, et al. Podocyte lesions in patients with obesity-related glomerulopathy. Am J Kidney Dis. 2006;48:772–9.

    Article  PubMed  Google Scholar 

  56. Bidani AK, Griffin KA. Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension. 2004;44:595–601.

    Article  CAS  PubMed  Google Scholar 

  57. Dworkin LD, Hostetter TH, Rennke HG, Brenner BM. Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. J Clin Invest. 1984;73:1448–61.

    Article  CAS  PubMed  Google Scholar 

  58. Endlich N, Sunohara M, Nietfeld W, et al. Analysis of differential gene expression in stretched podocytes: osteopontin enhances adaptation of podocytes to mechanical stress. FASEB J. 2002;16:1850–2.

    CAS  PubMed  Google Scholar 

  59. Durvasula RV, Petermann AT, Hiromura K, et al. Activation of a local tissue angiotensin system in podocytes by mechanical strain. Kidney Int. 2004;65:30–9.

    Article  CAS  PubMed  Google Scholar 

  60. Chen J, Muntner P, Hamm LL, et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med. 2004;140:167–74.

    PubMed  Google Scholar 

  61. Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol. 2005;16:2134–40.

    Article  PubMed  Google Scholar 

  62. Bochud M, Nussberger J, Bovet P, et al. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension. 2006;48:239–45.

    Article  CAS  PubMed  Google Scholar 

  63. Kidambi S, Kotchen JM, Grim CE, et al. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks. Hypertension. 2007;49:704–11.

    Article  CAS  PubMed  Google Scholar 

  64. Russo P, Lauria F, Loguercio M, et al. 344C/T Variant in the promoter of the aldosterone synthase gene (CYP11B2) is associated with metabolic syndrome in men. Am J Hypertens. 2007;20:218–22.

    Article  CAS  PubMed  Google Scholar 

  65. Fallo F, Veglio F, Bertello C, et al. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab. 2006;91:454–9.

    Article  CAS  PubMed  Google Scholar 

  66. Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension. 2004;43:518–24.

    Article  CAS  PubMed  Google Scholar 

  67. Goodfriend TL, Ball DL, Egan BM, Campbell WB, Nithipatikom K. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Hypertension. 2004;43:358–63.

    Article  CAS  PubMed  Google Scholar 

  68. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci U S A. 2003;100:14211–6.

    Article  CAS  PubMed  Google Scholar 

  69. Guo C, Martinez-Vasquez D, Mendez GP, et al. Mineralocorticoid receptor antagonist reduces renal injury in rodent models of types 1 and 2 diabetes mellitus. Endocrinology. 2006;147:5363–73.

    Article  CAS  PubMed  Google Scholar 

  70. Kumar JM, Brooks DP, Olson BA, Laping NJ. Sgk, a putative serine/threonine kinase, is differentially expressed in the kidney of diabetic mice and humans. J Am Soc Nephrol. 1999;10:2488–94.

    CAS  PubMed  Google Scholar 

  71. Kim KY, Kim HY, Kim JH, et al. Tumor necrosis factor-alpha and interleukin-1beta increases CTRP1 expression in adipose tissue. FEBS Lett. 2006;580:3953–60.

    Article  CAS  PubMed  Google Scholar 

  72. Jeon JH, Kim KY, Kim JH, et al. A novel adipokine CTRP1 stimulates aldosterone production. FASEB J. 2008;22:1502–11.

    Article  CAS  PubMed  Google Scholar 

  73. Verhave JC, Hillege HL, Burgerhof JG, et al. Sodium intake affects urinary albumin excretion especially in overweight subjects. J Intern Med. 2004;256:324–30.

    Article  CAS  PubMed  Google Scholar 

  74. Matsui H, Ando K, Kawarazaki H, et al. Salt excess causes left ventricular diastolic dysfunction in rats with metabolic disorder. Hypertension. 2008;52:287–94.

    Article  CAS  PubMed  Google Scholar 

  75. Bridgham JT, Carroll SM, Thornton JW. Evolution of hormone-receptor complexity by molecular exploitation. Science. 2006;312:97–101.

    Article  CAS  PubMed  Google Scholar 

  76. Nagata K, Obata K, Xu J, et al. Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and failure in low-aldosterone hypertensive rats. Hypertension. 2006;47:656–64.

    Article  CAS  PubMed  Google Scholar 

  77. Le Menuet D, Isnard R, Bichara M, et al. Alteration of cardiac and renal functions in transgenic mice overexpressing human mineralocorticoid receptor. J Biol Chem. 2001;276:38911–20.

    Article  CAS  PubMed  Google Scholar 

  78. Ouvrard-Pascaud A, Sainte-Marie Y, Benitah JP, et al. Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias. Circulation. 2005;111:3025–33.

    Article  CAS  PubMed  Google Scholar 

  79. Kato S, Endoh H, Masuhiro Y, et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 1995;270:1491–4.

    Article  CAS  PubMed  Google Scholar 

  80. Yanagisawa J, Yanagi Y, Masuhiro Y, et al. Convergence of transforming growth factor-beta and vitamin D signaling pathways on SMAD transcriptional coactivators. Science. 1999;283:1317–21.

    Article  CAS  PubMed  Google Scholar 

  81. Su LF, Knoblauch R, Garabedian MJ. Rho GTPases as modulators of the estrogen receptor transcriptional response. J Biol Chem. 2001;276:3231–7.

    Article  CAS  PubMed  Google Scholar 

  82. Kino T, Souvatzoglou E, Charmandari E, et al. Rho family Guanine nucleotide exchange factor Brx couples extracellular signals to the glucocorticoid signaling system. J Biol Chem. 2006;281:9118–26.

    Article  CAS  PubMed  Google Scholar 

  83. Togawa A, Miyoshi J, Ishizaki H, et al. Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha. Oncogene. 1999;18:5373–80.

    Article  CAS  PubMed  Google Scholar 

  84. Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci U S A. 2004;101:7618–23.

    Article  CAS  PubMed  Google Scholar 

  85. Cancelas JA, Lee AW, Prabhakar R, et al. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med. 2005;11:886–91.

    Article  CAS  PubMed  Google Scholar 

  86. Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev. 2001;81:153–208.

    CAS  PubMed  Google Scholar 

  87. Wu X, Tu X, Joeng KS, et al. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell. 2008;133:340–53.

    Article  CAS  PubMed  Google Scholar 

  88. Kawashima T, Bao YC, Nomura Y, et al. Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors. J Cell Biol. 2006;175:937–46.

    Article  CAS  PubMed  Google Scholar 

  89. Ando K, Ohtsu H, Arakawa Y, et al. Rationale and design of the eplerenone combination versus conventional agents to lower blood pressure on urinary antialbuminuric treatment effect (EVALUATE) trial: a double-blinded randomized placebo-controlled trial to evaluate the antialbuminuric effects of an aldosterone blocker in hypertensive patients with albuminuria. Hypertens Res. 2010.

Download references

Acknowledgments

I would like to express my deepest gratitude to Dr. T. Fujita (University of Tokyo) for his mentorship and continuous support and encouragement; Dr. S. Hirose (Tokyo Institute of Technology) for introducing me to molecular biology; and Drs. Y. Takai, J. Miyoshi, H. Tanaka, H. Kurihara, H. Kawachi, S. Kaname, K. Ando, T. Gotoda, T. Masaki, T, Sawamura, J. Ando, S. Shibata, S. Yoshida, H. Matsui, W. Kawarazaki, M. Takeuchi, K. Ishizawa, and N. Ayuzawa for their collaboration and helpful discussions.

Author information

Authors and Affiliations

  1. Division of Chronic Kidney Disease, Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Miki Nagase

Authors
  1. Miki Nagase
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miki Nagase.

About this article

Cite this article

Nagase, M. Activation of the aldosterone/mineralocorticoid receptor system in chronic kidney disease and metabolic syndrome. Clin Exp Nephrol 14, 303–314 (2010). https://doi.org/10.1007/s10157-010-0298-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-010-0298-8

Keywords

Search

Navigation