Haemodynamic frailty – A risk factor for acute kidney injury in the elderly

Clinical frailty in the elderly is defined by a composite measure of functional psychomotor decline. Herein, we develop the concept of haemodynamic frailty (HDF), a state of increased predisposition to disease prevalent in the elderly and characterised by impairment of the network of compensatory responses governing the defence of circulatory volume and adaptive haemodynamic function. We review the factors predisposing the elderly to HDF, with a focus on the impaired capacity to sustain total body water balance. As a component of HDF, dehydration generates vulnerability to diseases caused by tissue hypoperfusion, including acute kidney injury. We provide a detailed mechanistic explanation of how dehydration and depletion of the intravascular volume impacts on renal blood flow to become an important element of the heightened risk of acute kidney injury (AKI) in the elderly. We bring these mechanistic considerations into the clinical context with reference to examples of how pre-renal (haemodynamic) and intrinsic (involving renal parenchymal damage) AKI risk is elevated in the setting of dehydration. Finally, we present HDF as a state of opportunity to prevent disease, for which diagnostic and interventional standards need to be refined. Further prospective studies are warranted to help clarify the clinical utility of assessing and managing HDF with regard to the mitigation of AKI risk in the elderly

Cell biology of nephrocalcinosis/nephrolithiasis

A dozen conditions are regularly associated with nephrocalcinosis, and two dozen more less frequently. Mechanisms of intratubular and interstitial crystal formation, and propagation or removal, as well as inhibitors of crystal formation, are described.</p

Epithelial Cell Cycle Behaviour in the Injured Kidney

Acute kidney injury (AKI), commonly caused by ischemia-reperfusion injury, has far-reaching health consequences. Despite the significant regenerative capacity of proximal tubular epithelium cells (PTCs), repair frequently fails, leading to the development of chronic kidney disease (CKD). In the last decade, it has been repeatedly demonstrated that dysregulation of the cell cycle can cause injured kidneys to progress to CKD. More precisely, severe AKI causes PTCs to arrest in the G1/S or G2/M phase of the cell cycle, leading to maladaptive repair and a fibrotic outcome. The mechanisms causing these arrests are far from known. The arrest might, at least partially, be attributed to DNA damage since activation of the DNA-damage response pathway leads to cell cycle arrest. Alternatively, cytokine signalling via nuclear factor kappa beta (NF-&kappa;&beta;) and p38-mitogen-activated protein kinase (p38-MAPK) pathways, and reactive oxygen species (ROS) can play a role independent of DNA damage. In addition, only a handful of cell cycle regulators (e.g., p53, p21) have been thoroughly studied during renal repair. Still, why and how PTCs decide to arrest their cell cycle and how this arrest can efficiently be overcome remain open and challenging questions. In this review we will discuss the evidence for cell cycle involvement during AKI and development of CKD together with putative therapeutic approaches

Short-term dexamethasone treatment transiently, but not permanently, attenuates fibrosis after acute-to-chronic kidney injury

Figure S4. Original blots of F4/80 and α-SMA protein expression. Dex/Veh Wk3: Animals were euthanized after treatment with dexamethasone/vehicle respectively (3 weeks after UIRI); Dex/Veh Wk6: animals were euthanized 3 weeks after treatment with dexamethasone/vehicle respectively (6 weeks after UIRI); Untreated: animals were euthanized 3 weeks after UIRI; Sham: animals were euthanized 6 weeks after mock-UIRI. A: Original Western Blot of F4/80 macrophage/monocyte and β-actin protein expression. It should be noted that under non-reducing circumstances the molecular weight of F4/80 is 102 kDa. For reducing circumstances (i.e. boiling in 2-mercaptoethanol), as used in our study, Starkey et al. [38] reported that the antigen is cleaved in two fragments of 20 kDa and 80 kDa, the latter of which detected in our analysis. B: Original Western Blot of α-SMA macrophage/monocyte and β-actin protein expression. (JPG 439 kb