SAT-058 Histopathological Analysis of Kidneys and Adrenal Glands in the Same Primary Aldosteronism (PA) Patients: Exploring the Mechanisms of Aldosterone Specific Renal Injuries

Abstract

Primary aldosteronism (PA) is a major cause of secondary hypertension, accounting for 5 to 10% of all of the patients with hypertension. PA is also well known to harbor relatively higher incidence of cardiovascular complications than essential hypertension (EH) despite similar blood pressure levels. Among these complications, renal injuries are considered clinically important because up to 15% of APA (Aldosterone-producing adenoma) patients had already been chronic kidney disease at the time of its initial diagnosis (Iwakura et al., JCEM, 2014). In addition, PA patients are relatively younger than EH, which makes early clinical intervention pivotal. Many pathways of aldosterone-induced renal injuries have been proposed but the actual mechanism of aldosterone related injuries in human kidney has remained virtually unknown. Therefore, in this study, we performed the detailed histopathological analysis for kidneys and adrenal glands of the same PA patients and compared with those of EH. We analyzed 7 APA cases undergoing renal biopsy or nephrectomy with adrenalectomy. As a control group, 40 age-matched EH cases (31 autopsy, 9 biopsy) were examined. Digital image software (HALO, Indica Labs) was employed to perform quantitative histological analysis. There were no significant differences of eGFR between EH and PA before adrenalectomy (p=0.8111), but eGFR become lower in post-operative PA than in EH (p=0.0511). The prevalence of global glomerular sclerosis (GGS) and focal glomerular sclerosis (FGS) was significantly higher in PA than in EH (p=0.0031, 0.0035). Mesenchymal fibrosis was also more marked in PA than in EH (p=0.0091). Among the increased GGS groups (over 10%), the ratio of GGS/mesenchymal fibrosis tended to be lower in PA than in EH(p=0.0653). CYP11B2 positive area in adrenal cortex was more extended in autopsy EH than in adjacent cortex of PA (p=0.0209), and a significant correlation was also detected between CYP11B2 and renin immunoreactivity in autopsy EH adrenals (p=0.0067). In PA, CYP11B2 immunoreactivity in adenomas tended to be correlated with glomerular swelling (p=0.0539), probably reflecting the status of glomerular hyperfiltration. 11βHSD2 immunoreactivity of cortical tubules was significantly higher in PA than in EH (p=0.0001) and significantly correlated with the degree of renal arteriole hyalinization in PA (p<.0001). The renal injuries in PA demonstrated not only glomerular sclerosis but also mesenchymal fibrosis in contrast to kidneys of EH which predominantly demonstrated glomerular sclerosis. Higher 11βHSD2 expression in the tubules of PA kidneys could also enhance topical effects of aldosterone, resulting in renal arteriole hyalinization in PA. We firstly demonstrated the markedly different patterns of renal injuries between PA and EH patients and could contribute to the management of renal functions of these two different hypertensive disorders.