The loss of renal mass induces tubular hypertrophy as well as glomerular sclerosis and results in the end stage of renal disease. However, there is little information about adaptation of tubular glucose and peptide reabsorption under conditions of chronic renal failure. In the present study, we performed functional and molecular analyses focused on the tubular reabsorption of ˆltered glucose and small peptides using 5W6 nephrectomized rats at 16 weeks, as a model of chronic renal failure. Sixteen weeks after 5W6 nephrectomy or sham treatment, the brush-border membranes and total RNA were obtained from the renal cortex to evaluate the uptake of Na+ gradient-dependent D-glucose and H+ gradient-dependent glycylsarcosine. The amounts of SGLT and PEPT mRNA levels were quantiˆed by competitive PCR. The urinary glucoseWcreatinine ratio was markedly higher in nephrectomized rats than in sham-operated controls. Na+-dependent glucose uptake by the isolated renal brush-border membrane vesicles was markedly decreased in nephrectomized rats compared with that in sham-operated controls. However, H+-dependent peptide transport, another secondary active transport system in the brushborder membranes, was maintained. In addition, kinetic analysis revealed that both SGLT1 (high-a‹ nity type)-and SGLT2 (low-a‹ nity type)-mediated Na+ Wglucose uptake had markedly decreased Vmax values, but not Km values. Futhermore, competitive PCR demonstrated that the mRNA expression levels of SGLT2, PEPT1 and PEPT2, but not SGLT1, were markedly depressed. These ˆndings suggested that loss of SGLT2 during chronic renal failure implies a high risk of renal glucosuria.