mTORC2 critically regulates renal potassium handling

The mTOR pathway orchestrates cellular homeostasis. The rapamycin-sensitive mTOR complex (mTORC1) in the kidney has been widely studied; however, mTORC2 function in renal tubules is poorly characterized. Here, we generated mice lacking mTORC2 in the distal tubule (Rictorfl/fl Ksp-Cre mice), which were viable and had no obvious phenotype, except for a 2.5-fold increase in plasma aldosterone. Challenged with a low-Na+ diet, these mice adequately reduced Na+ excretion; however, Rictorfl/fl Ksp-Cre mice rapidly developed hyperkalemia on a high-K+ diet, despite a 10-fold increase in serum aldosterone levels, implying that mTORC2 regulates kaliuresis. Phosphorylation of serum- and glucocorticoid-inducible kinase 1 (SGK1) and PKC-α was absent in Rictorfl/fl Ksp-Cre mice, indicating a functional block in K+ secretion activation via ROMK channels. Indeed, patch-clamp experiments on split-open tubular segments from the transition zone of the late connecting tubule and early cortical collecting duct demonstrated that Ba2+-sensitive apical K+ currents were barely detectable in the majority of Rictorfl/fl Ksp-Cre mice. Conversely, epithelial sodium channel (ENaC) activity was largely preserved, suggesting that the reduced ability to maintain K+ homeostasis is the result of impaired apical K+ conductance and not a reduced electrical driving force for K+ secretion. Thus, these data unravel a vital and nonredundant role of mTORC2 for distal tubular K+ handling

State of the art in enzymatic debridement

Surgical treatment of deep partial thickness to full thickness burn wounds by knife has been the undisputed standard of care and was one key point in surgical burn medicine for decades. Recently, it gets more and more challenged by Bromelain-based enzymatic burn wound debridement (ED) as technique for non-surgical, selective eschar removal. Although the literature on ED is increasing constantly it cannot comprise the rapid progress that is made in clinical application of ED. To outline the current state of art in ED, recent literature as well as clinical experience is summarized and the main steps in clinical application including indications, wound preparation, application of the enzyme, wound bed assessment and further treatment after ED are discussed. Initial indications and limitations in application of ED could be gradually extended to increase versatility of ED as tool in burn surgery. Several randomized controlled trials compared ED to standard of care (SOC). They could show significant shorter time to complete burn wound debridement and wound closure, reduced need for surgery, reduced blood loss, reduced area of burns that needed surgical excision and need for autograft as well as an improved scar quality. Further research is necessary to justify an extensive use of ED as tool for burn eschar removal. Especially a robust comparison to surgical burn wound excision by knife as SOC is required to facilitate evidence-based burn surgery

Additional file 1: of Enzymatic debridement for the treatment of severely burned upper extremities – early single center experiences

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