METHODS: Scientific literature was thoroughly searched to find 1) DKA treatment guidelines, 2) studies reporting hypokalemia in DKA, 3) and literature elaborating mechanisms involved in hypokalemia.
RESULTS: Acidosis affects SK and its regulators including insulin, catecholamines and aldosterone. Current conceptual framework is an argument to gauge the degree of hypokalemia before it strikes DKA patients utilizing SK level after adjusting it with pH. Suggested approach will reduce hypokalemia risk and its associated complications. The nomogram calculates pH-adjusted potassium and expected potassium loss. It also ranks hypokalemia associated risk, and proposes the potassium-replacement rate over given time period. The differences between current DKA treatment guidelines and proposed strategy are also discussed. Moreover, reasons and risk of hyperkalemia due to early initiation of potassium replacement and remedial actions are debated.
CONCLUSION: In light of proposed strategy, utilizing the nomogram ensures reduced incidence of hypokalemia in DKA resulting in improved clinical and patient outcomes. Pharmacoeconomic benefits can also be expected when avoiding hypokalemia ensures early discharge.
OBJECTIVE: The objective of the study was to delineate a process in human ZG, which may regulate both aldosterone production and cell turnover.
DESIGN: This study included a comparison of 20 pairs of ZG and zona fasciculata transcriptomes from adrenals adjacent to an APA (n = 13) or a pheochromocytoma (n = 7).
INTERVENTIONS: Interventions included an overexpression of the top ZG gene (LGR5) or stimulation by its ligand (R-spondin-3).
MAIN OUTCOME MEASURES: A transcriptome profile of ZG and zona fasciculata and aldosterone production, cell kinetic measurements, and Wnt signaling activity of LGR5 transfected or R-spondin-3-stimulated cells were measured.
RESULTS: LGR5 was the top gene up-regulated in ZG (25-fold). The gene for its cognate ligand R-spondin-3, RSPO3, was 5-fold up-regulated. In total, 18 genes associated with the Wnt pathway were greater than 2-fold up-regulated. ZG selectivity of LGR5, and its absence in most APAs, were confirmed by quantitative PCR and immunohistochemistry. Both R-spondin-3 stimulation and LGR5 transfection of human adrenal cells suppressed aldosterone production. There was reduced proliferation and increased apoptosis of transfected cells, and the noncanonical activator protein-1/Jun pathway was stimulated more than the canonical Wnt pathway (3-fold vs 1.3-fold). ZG of adrenal sections stained positive for apoptosis markers.
CONCLUSION: LGR5 is the most selectively expressed gene in human ZG and reduces aldosterone production and cell number. Such conditions may favor cells whose somatic mutation reverses aldosterone inhibition and cell loss.