Regulation of the Na+/H+ antiporter in patients with mild chronic renal failure: effect of glucose.
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.
Tepel
M
M
Universitätsklinik Marienhospital, Ruhr-Universität-Bochum, Herne, Germany. Martin.Tepel@ruhr-uni-bochum.de
van der Giet
M
M
Brukamp
K
K
Weyer
J
J
Zidek
W
W
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D005947:Glucose