Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Unilateral adrenalectomy improves urinary protein excretion but does not abolish its relationship to sodium excretion in patients with aldosterone-producing adenoma

Abstract

Experimental and human data suggest that adverse cardiovascular (CV) and renal effects of aldosterone excess are dependent on concomitant dietary salt intake. Increased urinary protein (Uprot) is an early sign of nephropathy independently associated with CV risk. We have previously reported a positive association between Uprot and urinary sodium (UNa) in patients with hyperaldosteronism, but not in patients with normal aldosterone levels. We aimed to determine whether Uprot is related to UNa in patients with aldosterone-producing adenoma (APA) and whether the degree of Uprot and strength of this relationship is reduced following correction of hyperaldosteronism. Subjects with APA (n=24) underwent measurement of 24 h Uprot and UNa before and after unilateral adrenalectomy (follow-up 15.0±11.9 months). Following surgery, mean clinic systolic blood pressure fell (150.4±18.2 vs 134.5±14.5 mm Hg, P=0.0008), despite a reduction in number of antihypertensive medications, and Uprot (211.2±101.6 vs 106.0±41.8 mg per day, P<0.0001) decreased. There was a positive correlation between Uprot and UNa both before (r=0.5477, P=0.0056) and after (r=0.5097, P=0.0109) adrenalectomy. Changes in UNa independently predicted Uprot reduction (P=0.0189). These findings suggest that both aldosterone levels and dietary salt contribute to renal damage, and that once glomerular damage occurs it is not completely resolved following correction of hyperaldosteronism. Our study suggests that treatment strategies based on reduction of aldosterone effects, by adrenalectomy or mineralocorticoid receptor blockade, in conjunction with low-salt diet would provide additional target-organ protection in patients with primary aldosteronism.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Conn JW . Presidential address. I. Painting background. II. Primary aldosteronism, a new clinical syndrome. J Lab Clin Med 1955; 45 (1): 3–17.

    CAS  PubMed  Google Scholar 

  2. Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93 (9): 3266–3281.

    Article  CAS  PubMed  Google Scholar 

  3. Pimenta E, Calhoun DA . Primary aldosteronism: diagnosis and treatment. J Clin Hypertens (Greenwich) 2006; 8 (12): 887–893.

    Article  Google Scholar 

  4. Stowasser M, Gordon RD, Gunasekera TG, Cowley DC, Ward G, Archibald C et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after ‘non-selective’ screening of hypertensive patients. J Hypertens 2003; 21 (11): 2149–2157.

    Article  CAS  PubMed  Google Scholar 

  5. Lim PO, Dow E, Brennan G, Jung RT, MacDonald TM . High prevalence of primary aldosteronism in the Tayside hypertension clinic population. J Hum Hypertens 2000; 14 (5): 311–315.

    Article  CAS  PubMed  Google Scholar 

  6. Mosso L, Carvajal C, Gonzalez A, Barraza A, Avila F, Montero J et al. Primary aldosteronism and hypertensive disease. Hypertension 2003; 42 (2): 161–165.

    Article  CAS  PubMed  Google Scholar 

  7. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C et al. A prospective study of the prevalence of primary aldosteronism in 1125 hypertensive patients. J Am Coll Cardiol 2006; 48 (11): 2293–2300.

    Article  CAS  PubMed  Google Scholar 

  8. Stowasser M, Gordon RD, Rutherford JC, Nikwan NZ, Daunt N, Slater GJ . Diagnosis and management of primary aldosteronism. J Renin Angiotensin Aldosterone Syst 2001; 2 (3): 156–169.

    Article  CAS  PubMed  Google Scholar 

  9. Stowasser M, Gordon RD . Primary aldosteronism—careful investigation is essential and rewarding. Mol Cell Endocrinol 2004; 217 (1–2): 33–39.

    Article  CAS  PubMed  Google Scholar 

  10. Sukor N, Kogovsek C, Gordon RD, Robson D, Stowasser M . Improved quality of life, blood pressure, and biochemical status following laparoscopic adrenalectomy for unilateral primary aldosteronism. J Clin Endocrinol Metab 2010; 95 (3): 1360–1364.

    Article  CAS  PubMed  Google Scholar 

  11. Stowasser M, Klemm SA, Tunny TJ, Storie WJ, Rutherford JC, Gordon RD . Response to unilateral adrenalectomy for aldosterone-producing adenoma: effect of potassium levels and angiotensin responsiveness. Clin Exp Pharmacol Physiol 1994; 21 (4): 319–322.

    Article  CAS  PubMed  Google Scholar 

  12. Rutherford JC, Taylor WL, Stowasser M, Gordon RD . Success of surgery for primary aldosteronism judged by residual autonomous aldosterone production. World J Surg 1998; 22 (12): 1243–1245.

    Article  CAS  PubMed  Google Scholar 

  13. Weber KT, Brilla CG . Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 1991; 83 (6): 1849–1865.

    Article  CAS  PubMed  Google Scholar 

  14. Young M, Fullerton M, Dilley R, Funder J . Mineralocorticoids, hypertension, and cardiac fibrosis. J Clin Invest 1994; 93 (6): 2578–2583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rocha R, Stier Jr CT, Kifor I, Ochoa-Maya MR, Rennke HG, Williams GH et al. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology 2000; 141 (10): 3871–3878.

    Article  CAS  PubMed  Google Scholar 

  16. Rocha R, Chander PN, Zuckerman A, Stier Jr CT . Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension 1999; 33 (1 Part 2): 232–237.

    Article  CAS  PubMed  Google Scholar 

  17. Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG . Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 2003; 63 (5): 1791–1800.

    Article  CAS  PubMed  Google Scholar 

  18. Sato A, Saruta T . Aldosterone-induced organ damage: plasma aldosterone level and inappropriate salt status. Hypertens Res 2004; 27 (5): 303–310.

    Article  CAS  PubMed  Google Scholar 

  19. Abbate M, Benigni A, Bertani T, Remuzzi G . Nephrotoxicity of increased glomerular protein traffic. Nephrol Dial Transplant 1999; 14 (2): 304–312.

    Article  CAS  PubMed  Google Scholar 

  20. Hillege HL, Janssen WM, Bak AA, Diercks GF, Grobbee DE, Crijns HJ et al. Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med 2001; 249 (6): 519–526.

    Article  CAS  PubMed  Google Scholar 

  21. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR . Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 2003; 63 (1): 225–232.

    Article  PubMed  Google Scholar 

  22. Irie F, Iso H, Sairenchi T, Fukasawa N, Yamagishi K, Ikehara S et al. The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. Kidney Int 2006; 69 (7): 1264–1271.

    Article  CAS  PubMed  Google Scholar 

  23. Tonelli M, Jose P, Curhan G, Sacks F, Braunwald E, Pfeffer M . Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial. BMJ 2006; 332 (7555): 1426.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002; 106 (14): 1777–1782.

    Article  CAS  PubMed  Google Scholar 

  25. Rossi GP, Bernini G, Desideri G, Fabris B, Ferri C, Giacchetti G et al. Renal damage in primary aldosteronism: results of the PAPY Study. Hypertension 2006; 48 (2): 232–238.

    Article  CAS  PubMed  Google Scholar 

  26. Halimi JM, Mimran A . Albuminuria in untreated patients with primary aldosteronism or essential hypertension. J Hypertens 1995; 13 (12 Part 2): 1801–1802.

    CAS  PubMed  Google Scholar 

  27. Ribstein J, Du Cailar G, Fesler P, Mimran A . Relative glomerular hyperfiltration in primary aldosteronism. J Am Soc Nephrol 2005; 16 (5): 1320–1325.

    Article  PubMed  Google Scholar 

  28. Pimenta E, Gaddam KK, Pratt-Ubunama MN, Nishizaka MK, Aban I, Oparil S et al. Relation of dietary salt and aldosterone to urinary protein excretion in subjects with resistant hypertension. Hypertension 2008; 51 (2): 339–344.

    Article  CAS  PubMed  Google Scholar 

  29. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42 (6): 1206–1252.

    Article  CAS  PubMed  Google Scholar 

  30. Gordon RD . Primary aldosteronism. J Endocrinol Invest 1995; 18 (7): 495–511.

    Article  CAS  PubMed  Google Scholar 

  31. Jonsson JR, Klemm SA, Tunny TJ, Stowasser M, Gordon RD . A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension. Biochem Biophys Res Commun 1995; 207 (2): 565–571.

    Article  CAS  PubMed  Google Scholar 

  32. Stowasser M, Gordon RD . The aldosterone-renin ratio in screening for primary aldosteronism. Endocrinologist 2004; 14 (5): 267–276.

    Article  CAS  Google Scholar 

  33. Haber E, Koerner T, Page LB, Kliman B, Purnode A . Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab 1969; 29 (10): 1349–1355.

    Article  CAS  PubMed  Google Scholar 

  34. Ferrari P, Shaw SG, Nicod J, Saner E, Nussberger J . Active renin versus plasma renin activity to define aldosterone-to-renin ratio for primary aldosteronism. J Hypertens 2004; 22 (2): 377–381.

    Article  CAS  PubMed  Google Scholar 

  35. Mayes D, Furuyama S, Kem DC, Nugent CA . A radioimmunoassay for plasma aldosterone. J Clin Endocrinol Metab 1970; 30 (5): 682–685.

    Article  CAS  PubMed  Google Scholar 

  36. Perschel FH, Schemer R, Seiler L, Reincke M, Deinum J, Maser-Gluth C et al. Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays. Clin Chem 2004; 50 (9): 1650–1655.

    Article  CAS  PubMed  Google Scholar 

  37. Sechi LA, Novello M, Lapenna R, Baroselli S, Nadalini E, Colussi GL et al. Long-term renal outcomes in patients with primary aldosteronism. JAMA 2006; 295 (22): 2638–2645.

    Article  CAS  PubMed  Google Scholar 

  38. Catena C, Colussi G, Sechi LA . Renal function in primary aldosteronism. Hypertension 2006; 48 (6): e110; author reply e111.

    Article  CAS  PubMed  Google Scholar 

  39. Fox CS, Larson MG, Hwang SJ, Leip EP, Rifai N, Levy D et al. Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample. Kidney Int 2006; 69 (11): 2064–2069.

    Article  CAS  PubMed  Google Scholar 

  40. Weir MR, Dengel DR, Behrens MT, Goldberg AP . Salt-induced increases in systolic blood pressure affect renal hemodynamics and proteinuria. Hypertension 1995; 25 (6): 1339–1344.

    Article  CAS  PubMed  Google Scholar 

  41. Bigazzi R, Bianchi S, Baldari D, Sgherri G, Baldari G, Campese VM . Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors. Hypertension 1994; 23 (2): 195–199.

    Article  CAS  PubMed  Google Scholar 

  42. Sanders PW . Vascular consequences of dietary salt intake. Am J Physiol Renal Physiol 2009; 297 (2): F237–F243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sanders PW . Dietary salt intake, salt sensitivity, and cardiovascular health. Hypertension 2009; 53 (3): 442–445.

    Article  CAS  PubMed  Google Scholar 

  44. Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002; 283 (5): H1802–H1810.

    Article  CAS  PubMed  Google Scholar 

  45. Geerling JC, Loewy AD . Central regulation of sodium appetite. Exp Physiol 2008; 93 (2): 177–209.

    Article  CAS  PubMed  Google Scholar 

  46. Hollenberg NK . Aldosterone in the development and progression of renal injury. Kidney Int 2004; 66 (1): 1–9.

    Article  CAS  PubMed  Google Scholar 

  47. Arima S, Kohagura K, Xu HL, Sugawara A, Abe T, Satoh F et al. Nongenomic vascular action of aldosterone in the glomerular microcirculation. J Am Soc Nephrol 2003; 14 (9): 2255–2263.

    Article  CAS  PubMed  Google Scholar 

  48. Uhrenholt TR, Schjerning J, Hansen PB, Norregaard R, Jensen BL, Sorensen GL et al. Rapid inhibition of vasoconstriction in renal afferent arterioles by aldosterone. Circ Res 2003; 93 (12): 1258–1266.

    Article  CAS  PubMed  Google Scholar 

  49. Matavelli LC, Zhou X, Varagic J, Susic D, Frohlich ED . Salt loading produces severe renal hemodynamic dysfunction independent of arterial pressure in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 2007; 292 (2): H814–H819.

    Article  CAS  PubMed  Google Scholar 

  50. Yu HC, Burrell LM, Black MJ, Wu LL, Dilley RJ, Cooper ME et al. Salt induces myocardial and renal fibrosis in normotensive and hypertensive rats. Circulation 1998; 98 (23): 2621–2628.

    Article  CAS  PubMed  Google Scholar 

  51. Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ . Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45 (8): 1243–1248.

    Article  CAS  PubMed  Google Scholar 

  52. Tuomilehto J, Jousilahti P, Rastenyte D, Moltchanov V, Tanskanen A, Pietinen P et al. Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study. Lancet 2001; 357 (9259): 848–851.

    Article  CAS  PubMed  Google Scholar 

  53. Fallo F, Veglio F, Bertello C, Sonino N, Della Mea P, Ermani M et al. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab 2006; 91 (2): 454–459.

    Article  CAS  PubMed  Google Scholar 

  54. Bochud M, Nussberger J, Bovet P, Maillard MR, Elston RC, Paccaud F et al. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension 2006; 48 (2): 239–245.

    Article  CAS  PubMed  Google Scholar 

  55. Matrozova J, Steichen O, Amar L, Zacharieva S, Jeunemaitre X, Plouin PF . Fasting plasma glucose and serum lipids in patients with primary aldosteronism: a controlled cross-sectional study. Hypertension 2009; 53 (4): 605–610.

    Article  CAS  PubMed  Google Scholar 

  56. Pimenta E, Calhoun DA . Aldosterone and metabolic dysfunction: an unresolved issue. Hypertension 2009; 53 (4): 585–586.

    Article  CAS  PubMed  Google Scholar 

  57. Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R et al. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008; 168 (1): 80–85.

    Article  CAS  PubMed  Google Scholar 

  58. Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P et al. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 2007; 50 (5): 911–918.

    Article  CAS  PubMed  Google Scholar 

  59. Young Jr WF . Primary aldosteronism--one picture is not worth a thousand words. Ann Intern Med 2009; 151 (5): 357–358.

    Article  PubMed  Google Scholar 

  60. Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR et al. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med 2009; 151 (5): 329–337.

    Article  PubMed  Google Scholar 

  61. Freel M, Ingram M, Fraser R, Dominiczak A, Davies E, Connell J . Aldosterone and sodium excess associate with albuminuria and glomerular hyperfiltration in a severely hypertensive cohort from the MRC BRIGHT Study. Hypertension 2009; 54 (4): e51.

    Google Scholar 

Download references

Acknowledgements

This work was supported by a Clinical Centre of Research Excellence in Cardiovascular Disease and Metabolic Disorders Grant awarded by the National Health and Medical Research Council of Australia.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E Pimenta.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pimenta, E., Gordon, R., Ahmed, A. et al. Unilateral adrenalectomy improves urinary protein excretion but does not abolish its relationship to sodium excretion in patients with aldosterone-producing adenoma. J Hum Hypertens 25, 592–599 (2011). https://doi.org/10.1038/jhh.2010.102

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2010.102

Keywords

This article is cited by

Search

Quick links