Regulation of the Na+/H+ antiporter in patients with mild chronic renal failure: Effect of glucose

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 (pH(i)), 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 ph(i), [Na+](i), and Na+/H+ antiporter activity was measured in lymphocytes using fluorescent dye techniques. Results. Under resting conditions, the pH(i) 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 pH(i)/second to 16.44 ± 1.37 x 10-3 ph(i)/second after one hour and to 14.06 ± 1.36 x 10-3 pH(i)/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 pH(i)/second to 6,00 ± 0.56 x 10-3 pH(i)/second after one hour and to 6.65 ± 0.64 x 10-3 ph(i)/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.