Alterations of intestinal barrier and microbiota in chronic kidney disease.

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.

Electrolyte Disorders Induced by Antineoplastic Drugs.

The use of antineoplastic drugs has a central role in treatment of patients affected by cancer but is often associated with numerous electrolyte derangements which, in many cases, could represent life-threatening conditions. In fact, while several anti-cancer agents can interfere with kidney function leading to acute kidney injury, proteinuria, and hypertension, in many cases alterations of electrolyte tubular handling and water balance occur. This review summarizes the mechanisms underlying the disturbances of sodium, potassium, magnesium, calcium, and phosphate metabolism during anti-cancer treatment. Platinum compounds are associated with sodium, potassium, and magnesium derangements while alkylating agents and Vinca alkaloids with hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH). Novel anti-neoplastic agents, such as targeted therapies (monoclonal antibodies, tyrosine kinase inhibitors, immunomodulators, mammalian target of rapamycin), can induce SIADH-related hyponatremia and, less frequently, urinary sodium loss. The blockade of epidermal growth factor receptor (EGFR) by anti-EGFR antibodies can result in clinically significant magnesium and potassium losses. Finally, the tumor lysis syndrome is associated with hyperphosphatemia, hypocalcemia and hyperkalemia, all of which represent serious complications of chemotherapy. Thus, clinicians should be aware of these side effects of antineoplastic drugs, in order to set out preventive measures and start appropriate treatments.

[Hyponatremia in clinical practice]. / L'iponatremia nella pratica clinica.

Hyponatremia is the most frequent electrolyte disorder in hospitalized patients and it is associated with unfavorable clinical outcomes as well as increased hospital costs. Its clinical presentation may be highly variable, ranging from asymptomaticity to neurologic emergencies with seizures or coma as signs of rapidly worsening cerebral edema. In these cases, prompt treatment is mandatory to avoid the patients death. On the other hand, in the case of gradual development of hyponatremia, it is imperative that its correction be also appropriately slow in order to avoid another neurological catastrophe, namely the osmotic demyelination syndrome. Whilst recent international guidelines and expert consensus agree on the approach to the treatment of acute severe and symptomatic hyponatremia, the recommendations on pharmacological therapy in chronic hyponatremia diverge, particularly as to the potential use of vasopressin antagonists. This review is aimed at summarizing essential aspects of epidemiology, pathophysiology and the diagnostic process of hyponatremia, to set the ground for a practical as well as evidence-based approach to treatment. As a guide through the discussion of the available evidence, a clinical case is presented in which the patients history and laboratory data are crucial for identifying the etiology of hyponatremia. The severe neurological signs at presentation justify an emergency treatment with hypertonic saline, as indicated. Subsequently, as the neurological emergency subsides, we discuss the need to revert the trend towards hypercorrection by an apparently counterintuitive approach, based in fact on sound pathophysiological grounds, with continuous infusion of hypotonic solutions and administration of desmopressin.