High prevalence of renal damage has been demonstrated in patients with primary aldosteronism (PA). However, the original mechanism and onset still be elucidated. The purpose of this study is to investigate the possible original mechanisms of renal damages in PA.Design and Method:
Consecutive 72 patients with aldosterone producing adenoma (APA) and 70 patients with essential hypertension (EH) participated. No patients had renal damages defined as eGFR (based on Cystatin C) < 60 ml/min/1.73m2 and/or urinary albumin (UACR) ≥ 30 mg/g Creatinine and diabetes mellitus defined as HbA1c (NGSP) ≥ 6.5 % and/or medical treatments. All APA patients had taken sufficient mineralocorticoid receptor antagonists (MRAs) until the day of adrenalectomy. Urine samples were collected in the morning at the day of diagnosis (as baseline) and at that of adrenalectomy. Urine total angiotensinogen (UAGTN, μg/gCreatinine) and liver-type fatty acid-binding protein (L-FABP, μg/gCreatinine) were measured. The former indicates the activated intrarenal renin-angiotensin system (RAS) due to podocyte injury in the glomerular and megalin dysfunction on the proximal tubular, and the latter is the antioxidant derived from proximal tubular in human.Results:
Age, sex distribution, blood pressure, eGFR, UACR, and plasma total AGTN were similar between two groups at baseline. Meanwhile, UAGTN and L-FABP were higher in APA than in EH (10.2 vs. 2.9, p < 0.0005; 5.1 vs. 2.8, p < 0.05). UAGTN and L-FABP in APA showed the correlation (r = 0.6212, p < 0.0001). In multivariate analysis limited to non-renal parameters, plasma aldosterone and plasma AGTN were correlated with UAGTN in APA. UAGTN and L-FABP were decreased after MRAs treatment (10.2 vs. 3.9, p < 0.05; 5.1 vs. 3.7, p < 0.005) and the declines of these markers were correlated with each other (r = 0.3097, p = 0.0102).Conclusions:
Activated intrarenal RAS due to podocyte injury in the glomerular and megalin dysfunction and oxidative stress in the proximal tubular which occur before microalbuminuria can be the original mechanisms of renal damage in PA.