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Objective: To determine whether antihypertensives will affect diagnostic accuracy of the aldosterone-to-renin ratio (ARR) to an extent that is clinically relevant. Methods: Confirmatory tests were used to confirm or exclude PA diagnosis. Area under the receiver operating characteristic curve (AUC), specificity and sensitivity of ARR performance in different conditions were calculated. Results: 208 PA and 78 essential hypertension (EH), and 125 PA and 206 EH patients, were included in the retrospective and prospective cohort, respectively. AUC of ARR on interfering medications was comparable to ARR off interfering medications (retrospective: 0.82 vs. 0.87, p= 0.20; prospective: 0.78 vs. 0.84, p= 0.07). At a threshold of 20 pg/μIU, the sensitivity of ARR on interfering medications was lower (11.1–23.2%) while the specificity was higher (10.2–15.2%) than ARR off interfering medications. However, when the ARR threshold on interfering medications was lowered to 10 pg/μIU, both the sensitivity (retrospective: 0.91 vs. 0.90, p= 0.61; prospective: 0.86 vs. 0.82, p= 0.39) and specificity (retrospective: 0.49 vs. 0.59, p= 0.20; prospective: 0.58 vs. 0.66, p= 0.10) were comparable to the ARR threshold off interfering medications. Conclusion: Using ARR to screen for PA whilst taking interfering antihypertensive drugs is feasible in most cases, but the ARR threshold needs to be reduced. Trial registration: ClinicalTrials.gov identifier: NCT04991961.

Accumulating evidence suggests that bisphenol A (BPA) exposure is associated with nonalcoholic fatty liver disease. Disruption of autophagy causes lipid accumulation in hepatocytes. Whether and how BPA regulates autophagy remains to be explored. We investigated the effect of BPA on autophagy in hepatocytes and examined the influence of BPA-regulated autophagy on hepatic lipid accumulation. Male CD1 mice were treated with BPA for 8 weeks, followed by histological and biochemical evaluation of liver lipids and autophagy. Also, the effects of BPA on autophagy and hepatic lipid accumulation were examined in primary hepatocytes and HepG2 cells. Lipid content in HepG2 cells and/or primary hepatocytes was increased obviously after BPA exposure. In addition, BPA exposure caused accumulation of autophagosomes in HepG2 cells and enhanced colocalization of Bodipy 493/503 with microtubule associated protein light-chain 3. These changes were accompanied with increased expression levels of p-mammalian target of rapamycin, p-p70S6 kinase, p-ULK1 and decreased expression levels of Atg5. BPA exposure also downregulated the expression of cathepsin L and decreased cytoplasmic retention of acridine orange in HepG2 cells. The impaired autophagic degradation was further evidenced by increased levels of p62 in BPA-treated HepG2 cells. At the whole animal level, BPA treatment induced lipid accumulation in livers of male CD1 mice, which was accompanied with changes in hepatic autophagy-related proteins. Moreover, induction of autophagy by Torin1 protected against BPA-induced lipid accumulation whereas suppression of autophagy by chloroquine exacerbated BPA-induced lipid accumulation in HepG2 cells. BPA dysregulates autophagy in hepatocytes, which is linked to BPA-induced hepatic lipid accumulation.

Compared with general obesity, abdominal obesity has been shown to be more closely correlated to chronic diabetic complications such as cardiovascular disease and diabetic retinopathy. The association between obesity and diabetic kidney disease is unclear. We did two independent studies, one cross-sectional study and one 5 year prospective study, to investigate the association of general and abdominal obesity with diabetic kidney disease.