Fasting in rats decreases plasma citrate levels and reduces urinary citrate excretion by the kidney. After 72 h of fasting, the endogenous renal citrate clearance was decreased and the fractional citrate excretion was 0.026 +/- 0.008 compared with 0.218 +/- 0.030 in control fed rats. To determine whether these findings result from an adaptation in citrate transport across the plasma membrane of the renal tubular cell, Na+ gradient-dependent [14C]citrate uptake was examined in brush-border membrane vesicles (BBMW) prepared from kidneys of fed and 72-h fasted rats. The initial rate (10 s) of Na+ gradient-stimulated uptake of 100 microM citrate was significantly increased in BBMW from kidneys of fasted rats (380 +/- 24.9 pmol/mg prot) compared with fed rats (255 +/- 24.9 pmol/mg prot). Arterial acid-base parameters from conscious animals were similar between the two groups. There was no significant difference in Na+-independent citrate uptake or in L-glutamine uptake measured at 20 s in BBMV from the kidneys of fasted compared with fed rats. An adaptation occurs in the brush-border membrane of the renal tubular cell of fasting rats, unrelated to systemic acidosis, that may result in increased reabsorption of citrate.