Adrenalectomy Improves the Long-Term Risk of End-Stage Renal Disease and Mortality of Primary Aldosteronism

Ying-Ying Chen; You-Hsien Hugo Lin; Wei-Chieh Huang; Eric Chueh; Likwang Chen; Shao-Yu Yang; Po-Chih Lin; Lian-Yu Lin; Yen-Hung Lin; Vin-Cent Wu; Tzong-Shinn Chu; Kwan Dun Wu

Disclosures

J Endo Soc. 2019;3(6):1110-1126. 

In This Article

Abstract and Introduction

Abstract

Objective: Primary aldosteronism (PA) is a common cause of secondary hypertension, and the long-term effect of excess aldosterone on kidney function is unknown.

Patients and Methods: We used a longitudinal population database from the Taiwan National Health Insurance system and applied a validated algorithm to identify patients with PA diagnosed between 1997 and 2009.

Results: There were 2699 patients with PA recruited, of whom 761 patients with an aldosterone-producing adenoma (APA) were identified. The incidence rate of end-stage renal disease (ESRD) was 3% in patients with PA after targeted treatments and 5.2 years of follow-up, which was comparable to the rate in controls with essential hypertension (EH). However, after taking mortality as a competing risk, we found a significantly lower incidence of ESRD when comparing patients with PA vs EH [subdistribution hazard ratio (sHR), 0.38; P = 0.007] and patients with APA vs EH (sHR 0.55; P = 0.021) after adrenalectomy; however, we did not see similar results in groups with mineralocorticoid receptor antagonist (MRA)–treated PA vs EH. There was also a significantly lower incidence of mortality in groups with PA and APA who underwent adrenalectomy than among EH controls (P < 0.001).

Conclusion: Regarding incident ESRD, patients with PA were comparable to their EH counterparts after treatment. After adrenalectomy, patients with APA had better long-term outcomes regarding progression to ESRD and mortality than hypertensive controls, but MRA treatments did not significantly affect outcome.

Introduction

Primary aldosteronism (PA; i.e., autonomous aldosterone hypersecretion) is noted in 3.9% of patients with stage 1 hypertension, and the proportion increases to 11.8% in patients with stage 3 hypertension.[1] However, a number of cardiovascular and renal sequelae of PA cannot be entirely attributed to the effects of hypertension alone.[2] The reported risk of cardiovascular events was higher in patients with PA, with proinflammatory mediators and oxidative stress affecting multiple organs, than in otherwise similar patients with essential hypertension (EH).[3]

Prolonged aldosterone excess also causes relative kidney hyperfiltration and reversible intrarenal vascular structural changes, which disguise consequent renal injury, including declining glomerular filtration rate (GFR) and proteinuria.[4,5] Aldosterone has been reported to induce direct glomerular injury and proteinuria independently of its hemodynamic effects,[4,6] such as a high estimated GFR and albuminuria.[7] Hence, PA is associated with higher rates of renal blood flow[8] and, in a previous study, characterized by partially reversible renal dysfunction in which a dynamic, rather than structural, renal defect was demonstrated in a previous study.[9]

Although a long-term follow-up study with limited PA patients showed similar therapeutic effects on kidney function,[9] adrenalectomy and mineralocorticoid receptor antagonist (MRA) treatments have different short-term clinical impacts with respect to kidney damage, even with a similar blood pressure–lowering effect.[4,7,10] In fact, an initial temporary worsening of renal function within 1 month of adrenalectomy has been reported,[4,8,11] and the decline in renal function could be the result of correction of glomerular hyperfiltration via decreased aldosterone excess–related intrarenal vascular resistance[8] or systemic hemodynamic change.[12] A systemic review supported surgical resection of PA, which can be performed with low morbidity.[13] Adrenalectomy is safe, reverses aldosterone excess, and is effective at normalizing blood pressure and decreasing medication requirements, particularly in younger adults;[14] however, regarding kidney function, the long-term benefit/risk ratio of adrenalectomy compared with MRA treatment is lacking, and additional studies are warranted.

The Taiwan National Health Insurance research database contains records of claims that comprehensively capture information on episodes of care across all hospitals and nearly all health care facilities across Taiwan. Taking advantage of the merits of this database, we examined long-term crucial outcomes of renal events, namely end-stage renal disease (ESRD) and mortality among patients with PA receiving targeted treatment. We scrutinized the effects of different treatment options for PA on ESRD and mortality and subsequently explored the benefits of treatment strategies for reducing long-term ESRD and mortality risk among patients with PA.

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