title: Determination of the renal threshold for glucose excretion in Familial Renal Glucosuria.
abstract: OBJECTIVE
  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 (RTG) 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 RTG, according to a recently validated protocol.
  
  
  RESULTS
  In patients with homozygous mutations, RTG 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) RTG 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 RTG and increases in UGE. Because determination of RTG is not influenced by the filtered glucose load, the calculated RTG values provide a more refined measure of the impact of mutations on renal glucose transport than can be obtained from UGE alone.
authors.affiliation: Department of Nephrology, Hospital de Curry Cabral - CHLC, Lisbon, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Aires
authors.forename: Marc
authors.initials: M
authors.lastname: Fila
authors.forename: David
authors.initials: D
authors.lastname: Polidori
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Santos
authors.forename: Ana Brito
authors.initials: AB
authors.lastname: Costa
authors.forename: Joaquim
authors.initials: J
authors.lastname: Calado
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D005260:Female; D016368:Frameshift Mutation; D005919:Glomerular Filtration Rate; D005951:Glucose Tolerance Test; D006030:Glycosuria, Renal / Q000235:genetics* / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2