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  • Title: Regulation of the Na+/H+ antiporter in patients with mild chronic renal failure: effect of glucose.
    Author: Tepel M, van der Giet M, Brukamp K, Weyer J, Zidek W.
    Journal: Kidney Int; 1999 Jul; 56(1):172-80. PubMed ID: 10411690.
    Abstract:
    BACKGROUND: The aim of this study was to determine the glucose-dependent regulation of the sodium-proton-antiporter (Na+/H+ antiporter) in patients with mild chronic renal failure (CRF). METHODS: We measured plasma glucose concentrations, plasma insulin concentrations, plasma C peptide concentrations, arterial blood pressure, cytosolic pH (pHi), cellular Na+/H+ antiporter activity, and cytosolic sodium concentration ([Na+]i) in 19 patients with CRF and 41 age-matched healthy control subjects (control) during a standardized oral glucose tolerance test. Intracellular pHi, [Na+]i, and Na+/H+ antiporter activity was measured in lymphocytes using fluorescent dye techniques. RESULTS: Under resting conditions, the pHi was significantly lower, whereas the Na+/H+ antiporter activity was significantly higher in CRF patients compared with controls (each P < 0.0001). The oral administration of 100 g glucose significantly increased the Na+/H+ antiporter activity in CRF patients from 13.35 +/- 1.26 x 10-3 pHi/second to 16.44 +/- 1.37 x 10-3 pHi/second after one hour and to 14.06 +/- 1.36 x 10-3 pHi/second after two hours (mean +/- SEM, P = 0.008 by Friedmans's two-way analysis of variance). In controls, the administration of 100 g glucose significantly increased the Na+/H+ antiporter activity from 4.23 +/- 0.20 x 10-3 pHi/second to 6.00 +/- 0.56 x 10-3 pHi/second after one hour and to 6.65 +/- 0.64 x 10-3 pHi/second after two hours (P = 0.0003). The glucose-induced enhancement of the Na+/H+ antiporter activity was more pronounced in CRF patients compared with controls (P = 0.011). Resting [Na+]i was not significantly different between the two groups. CONCLUSIONS: CRF patients show an intracellular acidosis leading to an increased Na+/H+ antiporter activity. In addition, high glucose levels exaggerate the differences in Na+/H+ antiporter activity already present between cells from patients with mild CRF and those from control subjects.
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