This study demonstrates that the iv SLT is a reasonably good alternative to the more expensive and complex FST for the diagnosis of PA after a positive screening test.

Recent studies have highlighted the close relationship between the kidney and the gastrointestinal (GI) tract--frequently referred to as the kidney--gut axis--in patients with chronic kidney disease (CKD). In this regard, two important pathophysiological concepts have evolved: (i) production and accumulation of toxic end-products derived from increased bacterial fermentation of protein and other nitrogen-containing substances in the GI tract, (ii) translocation of endotoxins and live bacteria from gut lumen into the bloodstream, due to damage of the intestinal epithelial barrier and quantitative/qualitative alterations of the intestinal microbiota associated with the uraemic milieu. In both cases, these gut-centred alterations may have relevant systemic consequences in CKD patients, since they are able to trigger chronic inflammation, increase cardiovascular risk and worsen uraemic toxicity. The present review is thus focused on the kidney-gut axis in CKD, with special attention to the alterations of the intestinal barrier and the local microbiota (i.e. the collection of microorganisms living in a symbiotic coexistence with their host in the intestinal lumen) and their relationships to inflammation and uraemic toxicity in CKD. Moreover, we will summarize the most important clinical data suggesting the potential for nutritional modulation of gut-related inflammation and intestinal production of noxious by-products contributing to uraemic toxicity in CKD patients.

The relationship between pain and hypertension is potentially of great pathophysiological and clinical interest, but is poorly understood. The perception of acute pain initially plays an adaptive role, which results in the prevention of tissue damage. The consequence of ascending nociception is the recruitment of segmental spinal reflexes through the physiological neuronal connections. In proportion to the magnitude and duration of the stimulus, these spinal reflexes cause the activation of the sympathetic nervous system, which increases peripheral resistances, heart rate, and stroke volume. The response also involves the neuroendocrine system, and, in particular, the hypothalamic‐pituitary‐adrenal axis, in addition to further activation of the sympathetic system by adrenal glands. However, in proportion to an elevation in resting blood pressure, there is a contemporary and progressive reduction in sensitivity to acute pain, which could result in a tendency to restore arousal levels in the presence of painful stimuli. The pathophysiological pattern is significantly different in the setting of chronic pain, in which the adaptive relationship between blood pressure and pain sensitivity is substantially reversed. The connection between acute or chronic pain and cardiovascular changes is supported observationally, but some of this indirect evidence is confirmed by experimental models and human studies. The pain regulatory process and functional interaction between cardiovascular and pain regulatory systems are briefly reviewed. Various data obtained are described, together with their potential clinical implications.

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Sepsis is a serious medical condition that can lead to multi-organ failure and shock, and it is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication of sepsis in critically ill patients, and often requires renal replacement therapy. The pathophysiology of AKI in sepsis has not yet been fully defined. In the past, classic theories were mainly focused on systemic hemodynamic derangements, underscoring the key role of whole kidney hypoperfusion due to reduced renal blood flow. However, a growing body of experimental and clinical evidence now shows that, at least in the early phase of sepsis-associated AKI, renal blood flow is normal, or even increased. This could suggest a dissociation between renal blood flow and kidney function. In addition, the scant data available from kidney biopsies in human studies do not support diffuse acute tubular necrosis as the predominant lesion. Instead, increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction. Moreover, the same processes, through maladaptive responses leading to fibrosis acting from the very beginning, may set the stage for progression to chronic kidney disease in survivors from sepsis-associated AKI episodes. The aim of this narrative review is to summarize and discuss the latest evidence on the pathophysiological mechanisms involved in septic AKI, based on the most recent data from the literature.

IntroductionThe study was aimed at verifying whether the occurrence of hypernatremia during the intensive care unit (ICU) stay increases the risk of death in patients with severe traumatic brain injury (TBI). We performed a retrospective study on a prospectively collected database including all patients consecutively admitted over a 3-year period with a diagnosis of TBI (post-resuscitation Glasgow Coma Score ≤ 8) to a general/neurotrauma ICU of a university hospital, providing critical care services in a catchment area of about 1,200,000 inhabitants.MethodsDemographic, clinical, and ICU laboratory data were prospectively collected; serum sodium was assessed an average of three times per day. Hypernatremia was defined as two daily values of serum sodium above 145 mmol/l. The major outcome was death in the ICU after 14 days. Cox proportional-hazards regression models were used, with time-dependent variates designed to reflect exposure over time during the ICU stay: hypernatremia, desmopressin acetate (DDAVP) administration as a surrogate marker for the presence of central diabetes insipidus, and urinary output. The same models were adjusted for potential confounding factors.ResultsWe included in the study 130 TBI patients (mean age 52 years (standard deviation 23); males 74%; median Glasgow Coma Score 3 (range 3 to 8); mean Simplified Acute Physiology Score II 50 (standard deviation 15)); all were mechanically ventilated; 35 (26.9%) died within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the patients and in 15.9% of the 1,103 patient-day ICU follow-up. In most instances hypernatremia was mild (mean 150 mmol/l, interquartile range 148 to 152). The occurrence of hypernatremia was highest (P = 0.003) in patients with suspected central diabetes insipidus (25/130, 19.2%), a condition that was associated with increased severity of brain injury and ICU mortality. After adjustment for the baseline risk, the incidence of hypernatremia over the course of the ICU stay was significantly related with increased mortality (hazard ratio 3.00 (95% confidence interval: 1.34 to 6.51; P = 0.003)). However, DDAVP use modified this relation (P = 0.06), hypernatremia providing no additional prognostic information in the instances of suspected central diabetes insipidus.ConclusionsMild hypernatremia is associated with an increased risk of death in patients with severe TBI. In a proportion of the patients the association between hypernatremia and death is accounted for by the presence of central diabetes insipidus.

The presence of intestinal dysbiosis, along with increased intestinal permeability and high circulating levels of lipopolysaccharides, a condition known as "endotoxemia," characterize T2DM, CKD, and ESRD on dialysis. The hallmark of intestinal dysbiosis is a reduction of saccharolytic microbes mainly producing short-chain fatty acids (SCFA) and, in the case of CKD/ESRD, an increase in proteolytic microbes that produce different substances possibly related to uremic toxicity. Dysbiosis is associated with endotoxemia and chronic inflammation, with disruption of the intestinal barrier and depletion of beneficial bacteria producing SCFAs. T2DM and CKD/ESRD, whose coexistence is increasingly found in clinical practice, share similar negative effects on both intestinal microbiota and function. More studies are needed to characterize specific alterations of the intestinal microbiota in diabetic nephropathy and to assess possible effects of probiotic and prebiotic treatments in this setting.

In this study, myocardial E', A' and S' velocities, in both the left and the right ventricle, were significantly affected by preload in healthy subjects. Our results support the usefulness of the E'/A' ratio as a relatively load-independent index of diastolic function.