To investigate the effects of
uremia on cellular function the activity of the
sodium-dependent
chloride-bicarbonate exchanger (
sodium-dependent
Cl-/HCO3- exchanger) and the
sodium-independent
chloride-bicarbonate exchanger (
sodium-independent
Cl-/HCO3- exchanger) were examined in lymphocytes from 25 patients with mild
chronic renal failure, 9 patients with end-stage
chronic renal failure on regular
hemodialysis, and from 25 age-matched healthy control subjects. Cytosolic pH (pHi) and the activity of the
sodium-dependent
Cl-/HCO3- exchanger and the
sodium-independent
Cl-/HCO3- exchanger were measured spectrophotometrically using the pH-sensitive
fluorescent dye 2'7'-bis-carboxyethyl-5 [6]-
carboxyfluorescein acetoxy-methylester (
BCECF-AM). The activation of the
sodium-dependent
Cl-/HCO3- exchanger by removal of extracellular
chloride was prevented in the presence of 500 micromol/liter 4,4' diisothiocyanostilbene-2,2'-disulfonic
acid (
DIDS) or in the absence of extracellular
sodium, but was not affected by the specific inhibitor of the
sodium/
proton exchanger, ethyl isopropyl
amiloride (
EIPA). The
sodium-dependent
Cl-/HCO3- exchangers were significantly different in lymphocytes from healthy control subjects, patients with mild
chronic renal failure, and patients with end-stage
chronic renal failure (X2 = 6.43, P = 0.040 by Kruskal-Wallis-test). The
sodium-dependent
Cl-/HCO3- exchanger was significantly lower in patients with end-stage
chronic renal failure compared to patients with mild
chronic renal failure or compared to healthy control subjects (each P < 0.05). In patients with
chronic renal failure a significantly negative correlation between
sodium-dependent
Cl-/HCO3- exchanger and the serum
creatinine concentration (r = -0.507; P = 0.0022) could be observed. On the other hand, resting pHi in lymphocytes and
sodium-independent
Cl-/HCO3- exchanger were not significantly different in lymphocytes from healthy control subjects, patients with mild
chronic renal failure or patients with end-stage
chronic renal failure. The present study suggests that the activity of the
sodium-dependent
Cl-/HCO3- exchanger is progressively impaired in
chronic renal failure.