Primary aldosteronism, a common cause of severe hypertension1, features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II)2 and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of the identical p.Arg172Gln mutation; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in probands. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. Channel opening depolarizes glomerulosa cells and induces expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis. Mutant channels cause gain of function, with higher open probabilities at the glomerulosa resting potential. These findings for the first time demonstrate a role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. They establish the cause of a substantial fraction of early-onset primary aldosteronism.
Sensegiving constitutes a key process in the management of strategic change. Often this takes the form of narratives that provide a portrayal of events surrounding the change. This article reports the findings of research into the strategic change narratives that emerged in three organizations in which the senior management were seeking to respond to deregulation of the economy in which they were operating. The results illustrate both the existence of such narratives and the variation in form that they can take.
Post-streptococcal acute glomerulonephritis (PSAGN) is one of the most important and intriguing conditions in the discipline of pediatric nephrology. Although the eventual outcome is excellent in most cases, PSAGN remains an important cause of acute renal failure and hospitalization for children in both developed and underdeveloped areas. The purpose of this review is to describe both the typical and less common clinical features of PSAGN, to outline the changes in the epidemiology of PSAGN over the past 50 years, and to explore studies on the pathogenesis of the condition with an emphasis on the search for the elusive nephritogenic antigen.
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