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Metformin, belonging to a class of drugs called biguanides, is the recommended first-line treatment for overweight patients with type 2 diabetes mellitus. It has multiple mechanisms of action, such as reduction of gluconeogenesis, increases peripheral uptake of glucose, and decreases fatty acid oxidation. However, a potential serious complication, defined metformin-associated lactic acidosis (MALA), is related to increased plasma lactate levels, linked to an elevated plasma metformin concentrations and/or a coexistent condition altering lactate production or clearance. The mortality rate for MALA approaches 50% and metformin has been contraindicated in moderate and severe renal impairment, to minimize its potential toxic levels. Nevertheless, metformin prescription or administration, despite the presence of contraindications or precipitating factors for MALA, was a common topic highlighted in all reviewed papers. Routine assessment of metformin plasma concentration is not easily available in all laboratories, but plasma metformin concentrations measured in the emergency room could ensure the correct diagnosis, eliminating metformin as the cause of lactic acidosis if low plasma levels occurred. Renal replacement therapies have been successfully employed to achieve the correction of metabolic acidosis and rapidly remove metformin and lactate, but the optimal treatment modality for MALA is still controversial. [ABSTRACT FROM AUTHOR]

Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 ± 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 ± 0.6 ng/mL;p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels andKt/Vvalues, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy. [ABSTRACT FROM PUBLISHER]

Cancer anorexia-cachexia syndrome (CACS) is the most frequent paraneoplastic syndrome occurring in half of all oncologic patients and is considered as a poor prognosticator. Patients usually present with weight loss, lipolysis, muscle wasting, anorexia, chronic nausea, inflammation, and asthenia. The etiopathogenesis of CACS is still poorly understood, although several factors and biological pathways are known to be involved. Because of the complexity of this multifactorial condition, a single agent therapy may not be sufficient. Indeed, there is a tendency toward an integrated multiple approach including nonpharmacological and pharmacological treatments. However, despite encouraging preliminary results, currently there is not enough evidence to support a change in clinical practice. This review provides a brief and practical summary of the diagnosis, pathogenesis, and treatment of CACS. Future perspectives will also be discussed. [ABSTRACT FROM PUBLISHER]

The aquaporin-2 (AQP2) plays a key role in AVP-induced absorption of water, and its urinary excretion is related to its function. We aimed to test if the assumption of water with different mineral content can modify the expression of AQP2, leading to a change in AQP2 urinary concentration, in 20 healthy young subjects. Each subject received an oral water load (LM or HM) of 250 mL/hour for four hours, and several variables were measured. Plasmatic osmolality after water assumption was significantly reduced with no differences after the low (LM) or the high mineral (HM) water load. Urinary osmolality and plasmatic vasopressin concentration were significantly reduced after an assumption of both kinds of water. However, serum vasopressin was lower after HM water assumption than after LM. AQP2 urinary excretion was significantly reduced after water assumption with respect to the basal level and it was lower after LM than after HM water assumption. The different mineral content of water was investigated as a factor contributing to the development of hypertension. Considering that AQP2 can play a role in pathogenesis of hypertension, our demonstration that AVP-mediated AQP2 urinary excretion is strictly influenced by the consumption of water with different mineral content suggests a new, interesting field of investigation related to the link between blood pressure alterations and nutritional habits. [ABSTRACT FROM AUTHOR]

The kidney can achieve a structural and functional recovery after the damage induced by ischemia and reperfusion. This is due to the regeneration of epithelial tubular cells, the intervention of immature cells mainly localized in the medulla, and a small number of bone marrow-derived stem cells. In many instances, however, recovery is delayed or does not occur at all. The mechanisms allowing the renal cells to de-differentiate still need to be clarified in order to find a therapeutic approach that can amplify this ability and then stop the fibroid involution and the progression toward renal failure. Several authors have hypothesized a protective effect of EPO against ischemic and cytotoxic renal damage and observed that patients precociously treated with EPO showed a slower progression of renal failure. EPO has been demonstrated to have proliferative and anti-apoptotic effects in ischemia-reperfusion models in the brain and cell cultures. Moreover, EPO can mobilize stem cells and increase the plasmatic levels and the renal expression of VEGF. These effects seem to be dose-dependent and could be due to the activation of signal transduction systems, like Jak and STAT. In the presence of high doses of exogenous EPO or during the treatment with long-acting EPO-like molecules, non-specific receptors may be activated through a low-affinity link. Further investigations are needed to determine new therapeutic applications for EPO and other analogous hormones. Very long-acting molecules or molecules with cyto-protective but no erythropoietic effect may represent useful tools in the study of the molecular mechanisms underlying EPO's action and may have a rapid and safe therapeutic application. [ABSTRACT FROM AUTHOR]

Patients undergoing renal graft failure and returning to dialysis are often regarded to like facing for the first time a substitutive treatment, without considering the technical complications, the economical impact, and the psychological implications. This review attempt, to give answers to various questions, concerning the management of vascular access, the immunosuppressive therapy, the transplantectomy, the emotional and neuropsychic aspects, and the quality of life of graft-failed patients. [ABSTRACT FROM AUTHOR]