Of the 600-700 mg inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% may be extracted from the extracellular space. The origin of the other 90% of removed phosphate is unknown. This study tested the hypothesis that the main source of phosphate removed during hemodialysis is the intracellular compartment. Six binephrectomized pigs each underwent one 3-hour hemodialysis session, during which the extracorporeal circulation blood flow was maintained between 100 and 150 ml/min. To determine in vivo phosphate metabolism, we performed phosphorous ( 31 P) magnetic resonance spectroscopy using a 1.5-Tesla system and a surface coil placed over the gluteal muscle region. 31 P magnetic resonance spectra (repetition time =10 s; echo time =0.35 ms) were acquired every 160 seconds before, during, and after dialysis. During the dialysis sessions, plasma phosphate concentrations decreased rapidly (230.4 %; P=0.003) and then, plateaued before increasing approximately 30 minutes before the end of the sessions; 16 mmol phosphate was removed in each session. When extracellular phosphate levels plateaued, intracellular Pi content increased significantly (11%; P,0.001). Moreover, bATP decreased significantly (P,0.001); however, calcium levels remained balanced. Results of this study show that intracellular Pi is the source of Pi removed during dialysis. The intracellular Pi increase may reflect cellular stress induced by hemodialysis and/or strong intracellular phosphate regulation. 27: 206227: -206827: , 201627: . doi: 10.1681 Cardiovascular risks and mortality are significantly increased by hyperphosphatemia, which is associated with elevated parathormone levels and several adverse consequences, including effects on bone formation, mineralization and remodeling, and soft tissue and vascular calcification, 1 increasing the risk for cardiovascular events and mortality. 2,3 Usually, in patients on dialysis, hyperphosphatemia can be controlled by hemodialysis (HD) associated with a low-phosphate diet and the use of phosphate chelators. 2,4 During a standard HD session, around 600-700 mg phosphate is removed from the plasma, whereas it contains only 90 mg inorganic phosphate (Pi); 85% of phosphate is stored in the bones and teeth in hydroxyapatite form, 14% is stored in the intracellular space (90% organic phosphate and 10% Pi), and 1% remains in the extracellular space. J Am Soc Nephrol
Selenium (Se) is an essential element and deficit or excess of dietary Se is associated with health disorders. Relatively elevated Se levels have been reported in the Brazilian Amazon, where there are also important annual variations in the availability of different foods. The present study was conducted among six riparian communities of the Tapajo´s River to evaluate seasonal variations in blood and sequential hair cm Se concentrations, and to examine the relationships between Se in blood and hair, and blood and urine. Two cross-sectional studies were conducted, at the descending water (DWS, n ¼ 259) and the rising water (RWS, n ¼ 137) seasons, with repeated measures for a subgroup (n ¼ 112). Blood Se (B-Se), hair Se (H-Se) and urine Se (U-Se) were determined. Match-paired analyses were used for seasonal comparisons and the method of best fit was used to describe the relationships between biomarkers. B-Se levels presented a very large range (142-2447 mg/l) with no overall seasonal variation (median 284 and 292 mg/l, respectively). Sequential analysis of 13 cm hair strands showed significant variations over time: Se concentrations at the DWS were significantly lower compared with the rising water season (medians: 0.7 and 0.9 mg/g; ranges: 0.2-4.3 mg/g and 0.2-5.4 mg/g, respectively). At both seasons, the relationships between B-Se and H-Se were linear and highly significant (r 2 ¼ 67.9 and 63.6, respectively), while the relationship between B-Se and U-Se was best described by a sigmoid curve. Gender, age, education and smoking did not influence Se status or biomarker relationships. Variations in H-Se suggest that there may be seasonal availability of Se sources in local food. For populations presenting a large range and/or elevated Se exposure, sequential analyses of H-Se may provide a good reflection of variations in Se status.
BackgroundThere is experimental evidence that lethal ischemia-reperfusion injury (IRI) is largely due to mitochondrial permeability transition pore (mPTP) opening, which can be prevented by cyclosporine A (CsA). The aim of our study is to show that a higher dose of CsA (10 mg/kg) injected just before ischemia or a lower dose of CsA (3 mg/kg) injected further in advance of ischemia (1 h) protects the kidneys and improves mitochondrial function.MethodsAll mice underwent a right unilateral nephrectomy followed by 30 min clamping of the left renal artery. Mice in the control group did not receive any pharmacological treatment. Mice in the three groups treated by CsA were injected at different times and with different doses, namely 3 mg/kg 1 h or 10 min before ischemia or 10 mg/kg 10 min before ischemia. After 24 h of reperfusion, the plasma creatinine level were measured, the histological score was assessed and mitochondria were isolated to calculate the calcium retention capacity (CRC) and level of oxidative phosphorylation.ResultsMortality and renal function was significantly higher in the CsA 10 mg/kg-10 min and CsA 3mg/kg-1 h groups than in the CsA 3mg/kg-10 min group. Likewise, the CRC was significantly higher in the former two groups than in the latter, suggesting that the improved renal function was due to a longer delay in the opening of the mPTP. Oxidative phosphorylation levels were also higher 24 h after reperfusion in the protected groups.ConclusionsOur results suggest that the protection afforded by CsA is likely limited by its availability. The dose and timing of the injections are therefore crucial to ensure that the treatment is effective, but these findings may prove challenging to apply in practice.
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