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As our understanding of the physiology of the aldosterone-sensitive distal nephron (ASDN) advanced in light of novel acquisitions, mainly pertaining the regulation of key ion channels and transporters by with-no-lysine kinases, the pathophysiology of a variety of conditions affecting this segment of the nephron was partly or fully elucidated as well. The pathophysiology of tubulopathies affecting the ASDN or strictly related nephron segments, and disorders causing aldosteronism, pseudoaldosteronism and pseudohypoaldosteronism are here reviewed. The clinical features, with a strong emphasis on pathophysiology, of a variety of disorders are discussed, including: Liddle, Gordon (and calcineurin inhibitor-related hypertension), and Geller syndrome; apparent mineralocorticoid excess; Bartter and Gitelman syndromes; primary aldosteronism, including familial forms; generalized glucocorticoid resistance (Chrousos syndrome). Moreover, the pharmacological translational potential of such novel acquisitions is briefly discussed.

In recent years, our understanding of the physiology of the aldosterone-sensitive distal nephron (ASDN) has greatly advanced thanks to the discovery of the complex with-no-lysine kinase (WNK) signaling and the molecular characterization of the epithelial sodium channel (ENaC). A series of studies, initially focused on rare tubulopathies such as Gordon and Liddle syndromes, eventually led to a partial elucidation of the so-called "aldosterone paradox", the traditional explanation of the physiology of such disparate conditions such as hyperkalemia and low effective arterial blood volume. The physiology of the ASDN is herein illustrated in light of the novel acquisitions in an easy-to-understand fashion, with the aim of giving the practicing nephrologist a solid "first glance" into this exciting but challenging field. Focus is on ion channels and transporters, their regulation by key hormones such as aldosterone and angiotensin II, and dietary implications.

Background: Accelerated muscle wasting still represents a major issue in critically ill patients. However, a key problem in the intensive care unit is the lack of adequate tools for bedside evaluation of muscle mass. Moreover, when acute kidney injury (AKI) coexists, fluid overload and/or rapid fluid shifts due to renal replacement therapies that frequently occur and may interfere with muscle mass assessment. The purpose of this study is to validate muscle ultrasound (US) by a gold standard (muscle CT scan) for the assessment of quadriceps muscle thickness in critically ill patients with AKI., Methods: Quadriceps rectus femoris thickness and quadriceps vastus intermedius thickness of critically ill patients with AKI were blindly assessed at the same leg sites by both US and computed tomography (CT) scan. Using bivariate mixed-model linear regression analysis, we estimated, average difference in thickness between measurement sites, agreement (differential and proportional bias) of US compared to CT, and precision of the two methods, and eventually performed Bland-Altman analysis for repeated measurements on pooled results., Results: We analyzed 233 couples of measurements (30 patients). Average muscle thickness ranged between 1.0 and 1.6, depending on the measurement site. When comparing US to CT, both the observed differential bias (between + 0.04 and + 0.26 cm depending on the muscle site) and the proportional bias (between 82 and 98% of the reference values, depending on the muscle site) were not statistically significant. However, precision analysis showed that US scan tended to be slightly less precise in comparison to CT. Bland-Altman analysis on pooled results showed that the 95% limits of agreement between the US and CT were narrow, ranging from - 0.34 to + 0.36 cm., Conclusion: In critically ill patients with AKI, quadriceps muscle thickness assessment based on US is unbiased, although it occurs with a minor loss of precision compared to CT.