Renal Outcomes in Medically and Surgically Treated Primary Aldosteronism

Abstract

Lifelong therapy with mineralocorticoid receptor antagonists (MRAs) or surgical adrenalectomy are the recommended treatments for primary aldosteronism (PA). Whether these treatments mitigate the risk for kidney disease remains unknown. We performed a retrospective cohort study of patients with PA treated with MRAs (N=400) or surgical adrenalectomy (N=120) and age- and estimated glomerular filtration rate-matched patients with essential hypertension (N=15 474) to determine risk for chronic kidney disease and longitudinal estimated glomerular filtration rate decline. Despite similar blood pressures, patients with PA treated with MRAs had a higher risk for incident chronic kidney disease compared with essential hypertension patients (adjusted hazard ratio, 1.63; 95% confidence interval, 1.33-1.99). Correspondingly, the adjusted annual decline in estimated glomerular filtration rate was greater in PA patients treated with MRAs compared with essential hypertension patients (-1.6; 95% confidence interval, -1.4 to -1.8 versus -0.9; 95% confidence interval, -0.9 to -1.0 mL/min per 1.73 m2/y; P<0.001). In contrast, patients with unilateral PA treated with surgical adrenalectomy had no significant difference in risk for incident chronic kidney disease or in an annual decline in estimated glomerular filtration rate compared with essential hypertension patients. Among PA patients with diabetes mellitus treated with MRAs, there was a higher risk for incident albuminuria compared with essential hypertension (adjusted hazard ratio, 2.52; 95% confidence interval, 1.28-4.96). MRA therapy in PA is associated with higher risk for developing chronic kidney disease when compared with essential hypertension, and surgical adrenalectomy may mitigate this risk. When possible, curative surgical adrenalectomy may be superior to lifelong MRA therapy in preventing kidney disease in PA.

Keywords: adrenalectomy; blood pressure; essential hypertension; glomerular filtration rate; mineralocorticoid receptor antagonists.

Conflict of interest statement

Conflicts of Interest/Disclosures:

None

Figures

Figure 1. Derivation of study cohort

MR = mineralocorticoid receptor; PA = primary aldosteronism; ICD-9/10 = International Classification of Disease 9th or 10th Edition; eGFR = estimated glomerular filtration rate; CKD = chronic kidney disease.

Figure 2. Blood pressure trends in study cohort

PA = primary aldosteronism; MR = mineralocorticoid receptor; HTN = hypertension.

Figure 3. Standardized cumulative incidence curve of chronic kidney disease

Solid lines = adjusted cumulative incidence; dashed lines = unadjusted cumulative incidence. Incident chronic kidney disease defined as the combination of a decrease in eGFR to 2 in addition to an overall decline in eGFR of ≥ 15 mL/min/1.73 m2 from the value at study entry. HR adjusted for, and cumulative incidence curve standardized to the distribution of, the following variables at the time of study entry in our cohort: age, sex, race, diabetes mellitus, cardiovascular disease, eGFR, systolic blood pressure, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. HR = hazard ratio; PA = primary aldosteronism; EH = essential hypertension; MRA = mineralocorticoid receptor antagonist.

Figure 4. Mean eGFR throughout study period

Error bars represent +/− 1.96*standard error of the mean. eGFR = estimated glomerular filtration rate.