This large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients with AS.

The sequelae of diabetes mellitus include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury that is associated with a disruption in mitochondrial metabolic agility, inflammation and fibrosis. We explored the role of the innate immune complement component C5a, a potent mediator of inflammation, in the pathogenesis of DKD in clinical and experimental diabetes. Marked systemic elevation in C5a activity was demonstrated in patients with diabetes which was not therapeutically targeted by conventional renoprotective agents. C5a and its receptor (C5aR1) were upregulated early in the disease process and prior to manifest kidney injury in several diverse rodent models of diabetes. Genetic deletion of C5aR1 in mice conferred protection against diabetes-induced renal injury. Transcriptomic profiling of kidney revealed diabetes-induced downregulation of pathways involved in mitochondrial fatty acid metabolism. Interrogation of the lipidomics signature revealed abnormal cardiolipin remodelling in the diabetic kidney, a cardinal sign of disrupted mitochondrial architecture and bioenergetics. In vivo delivery of an orally active inhibitor of C5aR1 (PMX53) reversed the phenotypic changes and normalized the renal mitochondrial fatty acid profile, cardiolipin remodelling and citric acid cycle intermediates. In vitro exposure of human renal proximal tubular epithelial cells to C5a led to altered mitochondrial respiratory function and reactive oxygen species generation. These studies provide evidence for a pivotal role of the C5a/C5aR1 axis in propagating renal injury in the development of DKD via disruption of mitochondrial agility, establishing a new immunometabolic signalling pathway in DKD.

Background Adrenal vein sampling (AVS) is crucial for accurate lateralization of aldosterone excess but it is technically challenging due to the difficulty of adrenal vein cannulation. The use of adrenocorticotropic hormone (ACTH) to improve cannulation success is controversial and can lead to discordant lateralization outcomes. Objective To evaluate the utility of ACTH in two centres with different levels of AVS expertise and formulate a strategy for interpreting discordant results. Design A retrospective cross‐sectional analysis of AVS results and postoperative patient outcomes. Setting Two large tertiary hospitals with harmonized AVS protocols where adrenal venous samples are collected both before and after ACTH stimulation. Measurements Cannulation success (measured by selectivity index, SI), lateralization (measured by lateralization index, LI) and postoperative biochemical cure. Results Number of AVS procedures judged to have successful bilateral adrenal vein cannulation increased from 53% pre‐ to 73% post‐ACTH. The increase in cannulation success was significantly higher in centre where AVS was performed by multiple radiologists with a lower basal success rate. In both centres, the proportion of cases deemed to display lateralization significantly decreased with the use of ACTH (70% pre‐ to 52% post‐ACTH). Based on postoperative outcomes of patients with discordant results who underwent unilateral adrenalectomy, the combination of LI >3 pre‐ACTH and LI >2 post‐ACTH was predictive of a biochemical cure. Conclusion Adrenocorticotropic hormone can increase the rate of cannulation success during AVS at the expense of reduced lateralization. The criteria for lateralization should be carefully determined based on local data when ACTH is used.