Background/Aims: Familial Renal Glucosuria (FRG) is characterized by the presence of persistent isolated glucosuria in the absence of hyperglycemia. Mutations in SLC5A2, the gene coding for the sodium-glucose co-transporter 2 (SGLT2), are responsible for FRG. Phenotype/genotype correlations in FRG have mostly relied on the quantification of Urinary Glucose Excretion (UGE), which is dependent on both the filtered glucose load and the renal glucose reabsorptive capacity. In the current work, the renal threshold for glucose excretion (RT_G) was determined in an FRG cohort, with the purpose of characterizing the impact of SGLT2 mutations on renal glucose transport. Methods: From January to December of 2013, eight FRG individuals with identified SLC5A2 mutations were enrolled. Patients were given a Mixed-Meal Tolerance Test during which blood glucose and UGE were measured over a 4 h period and the data was used to calculate RT_G, according to a recently validated protocol. Results: In patients with homozygous mutations, RT_G values were very low, with a mean (SD) of 0.95 (1.17) mmol/l, compared to commonly reported values of approximately 10-11.1 mmol/l in healthy subjects. In subjects with heterozygous mutations, mean (SD) RT_G values were 4.91 (1.23) mmol/l, which are approximately one-half of the values in subjects without mutations. Conclusions: In FRG, mutations in SLC5A2 lead to reductions in RT_G and increases in UGE. Because determination of RT_G is not influenced by the filtered glucose load, the calculated RT_G values provide a more refined measure of the impact of mutations on renal glucose transport than can be obtained from UGE alone.

The cyclosporine-based regimen was independently associated with decreased adiposity and increased skeletal muscle compared with the tacrolimus-based regimen. Future randomized controlled trials are needed to confirm these findings.