June 14, 2006, Vol 295, No. 22 >

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Original Contribution | June 14, 2006

Long-term Renal Outcomes in Patients With Primary Aldosteronism FREE

Leonardo A. Sechi, MD; Marileda Novello, MD; Roberta Lapenna, MD; Sara Baroselli, MD; Elisa Nadalini, MD; Gian Luca Colussi, MD; Cristiana Catena, MD, PhD

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Author Affiliations: Hypertension Unit, Division of Internal Medicine, Department of Experimental and Clinical Pathology and Medicine, University of Udine, Udine, Italy.

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JAMA. 2006;295(22):2638-2645. doi:10.1001/jama.295.22.2638.

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ABSTRACT

Context Experimental animal studies indicate that exposure to increased aldosterone levels might result in renal damage, but the clinical evidence supporting this role of aldosterone is preliminary.

Objective To determine the long-term outcome of renal function in patients with primary aldosteronism after surgical or medical treatment.

Design, Setting, and Participants Prospective study conducted at an Italian university medical center among a consecutive sample of 50 patients who were diagnosed as having primary aldosteronism between January 1994 and December 2001 and who were followed up for a mean of 6.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with 100 patients with essential hypertension, matched for severity and duration of hypertension. All patients were treated with antihypertensive drugs to reach a target blood pressure of less than 140/90 mm Hg.

Main Outcome Measures Primary outcome measures were rates of change of glomerular filtration rate and albuminuria during follow-up. Detection of new-onset microalbuminuria and restoration of normal albumin excretion during follow-up were considered as secondary outcomes.

Results At baseline, glomerular filtration rate and albuminuria were higher in patients with primary aldosteronism than those with essential hypertension. The mean blood pressure during the study was 136/81 mm Hg in the primary aldosteronism group and 137/81 mm Hg in the essential hypertension group. Glomerular filtration rate and albuminuria declined during the initial 6-month period in both groups, with a change that was significantly greater (P<.001 for both variables) in patients with primary aldosteronism. Subsequent rate of decline of glomerular filtration was comparable in the 2 groups, whereas albuminuria did not progress in the remainder of the follow-up. Restoration of normal albumin excretion from microalbuminuria was significantly more frequent in primary aldosteronism than in essential hypertension (P = .02).

Conclusion In the majority of patients in this study, primary aldosteronism was characterized by partially reversible renal dysfunction in which elevated albuminuria is a marker of a dynamic rather than structural renal defect.

Primary aldosteronism is a form of endocrine hypertension characterized by high blood pressure, hypokalemia, suppressed plasma renin activity, and inappropriate aldosterone secretion. Recent studies have reported a greater frequency of primary aldosteronism among patients with hypertension than the previously accepted prevalence of approximately 1%.¹^- 2 Such increased frequency may be the result of more effective identification of this condition due to widespread use of the aldosterone-renin ratio as a screening test.³ Although primary aldosteronism is considered correctable with either removal of an adrenal adenoma or administration of mineralocorticoid receptor antagonists, in many cases, hypertension may persist after treatment.⁴

Primary aldosteronism has long been considered a relatively benign form of hypertension associated with low incidence of organ complications.⁵ This has been generally ascribed to the suppression of the renin-angiotensin axis that occurs as a result of an aldosterone-generated volume expansion.⁶ Recent experimental studies, however, suggest that long-term exposure to increased aldosterone levels might result in cardiovascular⁷ and renal⁸^- 9 structural damage, independent of the blood pressure level. Cardiovascular surrogate end points, including endothelial dysfunction, structural changes in resistance vessels, left ventricular hypertrophy, and impaired diastolic function, have been demonstrated in patients with primary aldosteronism,¹⁰ and indirect evidence of aldosterone-related damage has been obtained from clinical trials conducted in patients with heart failure who were treated with mineralocorticoid receptor antagonists, with significant decrease in the mortality rate.¹¹^- 12 The clinical evidence of a role of aldosterone as a potential contributor to renal dysfunction is weaker than that which has emerged for the cardiovascular system and has been summarized in thorough reviews.⁹^,13^- 14 Studies performed in patients with diabetic nephropathy¹⁵^- 17 and chronic kidney disease¹⁸^- 19 suggest a beneficial effect of aldosterone antagonists on urinary protein excretion, and a recent study has demonstrated increased albuminuria in patients with primary aldosteronism compared with patients with essential hypertension.²⁰ This study was designed to test the hypothesis that the excess renal damage found in primary aldosteronism is mainly related to a functional and reversible hemodynamic adaptation of the kidney and that treatment of primary aldosteronism can improve renal dysfunction, reflecting correction of this functional abnormality. We investigated the short-term and long-term outcomes of renal function in patients with primary aldosteronism who were followed up after either surgical or medical treatment.

METHODS

RESULTS

COMMENT

AUTHOR INFORMATION

Corresponding Author: Leonardo A. Sechi, MD, Clinica Medica, Università di Udine, Piazzale S. Maria della Misericordia 1, 33100 Udine, Italy (sechi@uniud.it).

Author Contributions: Dr Sechi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Sechi and Catena contributed equally to this work.

Study concept and design: Sechi, Catena.

Acquisition of data: Sechi, Novello, Lapenna, Baroselli, Nadalini, Colussi, Catena.

Analysis and interpretation of data: Sechi, Novello, Lapenna, Baroselli, Nadalini, Colussi, Catena.

Drafting of the manuscript: Sechi, Catena.

Critical revision of the manuscript for important intellectual content: Sechi, Novello, Lapenna, Baroselli, Nadalini, Colussi, Catena.

Statistical analysis: Sechi, Catena.

Obtained funding: Sechi, Novello, Colussi, Catena.

Administrative, technical, or material support: Sechi, Novello, Lapenna, Baroselli, Nadalini, Colussi, Catena.

Study supervision: Sechi, Novello, Lapenna, Baroselli, Nadalini, Colussi, Catena.

Financial Disclosures: None reported.

Funding/Support: This work was supported by research grants from the Italian Ministry of the University and Scientific and Technologic Research to Drs Sechi and Catena and by research grants from the Italian Society of Hypertension to Drs Novello and Colussi.

Role of the Sponsors: The research sponsors had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal