Disorders of Renal Glucose Transport
L. Leighton Hill
Primary renal glucosuria is a selective defect of proximal tubular glucose transport in which glucose is excreted in the urine at normal concentrations of blood glucose. The handling of all other filtered substances by the proximal tubules is normal, and the glucose transport defect is limited to the kidneys. The pattern of inheritance has been interpreted in some pedigrees to be autosomal dominant and in others to be autosomal recessive. Congenital renal glucosuria has been shown in at least one family with an autosomal recessive mode of inheritance to be a defect in the sodium glucose cotransporter gene (SGLT2). A defect in other sodium glucose cotransporter genes could be responsible for other types of primary renal glucosuria, such as the autosomal dominant varieties. At least two types of renal glucosuria are thought to occur, although establishing clinical differentiation sometimes is difficult. In one type, the maximum tubular reabsorptive capacity for glucose is low; that is, a reduced ability of almost all tubules to transport glucose occurs, resulting in reduction of both the minimal renal glucose threshold and the maximal tubular reabsorption. In another type, the maximum tubular reabsorptive capacity for glucose is normal, but a wide spectrum occurs in the ability of individual nephrons to reabsorb glucose, so the minimal renal glucose threshold is reduced despite the normal overall capacity of the proximal tubules to reabsorb glucose. A third and very rare type may involve abnormalities of several reabsorptive mechanisms and may result in very low rates of reabsorption of filtered glucose and a severe form of renal glucosuria. With the exception of this rare form, primary renal glucosuria almost always is clinically benign and asymptomatic and needs no therapy. However, it must be differentiated from diabetes mellitus by measuring glucose in blood and urine obtained nearly simultaneously via several random simultaneous tests or by performing a 3-hour glucose tolerance test. If the patient has renal glucosuria, the blood glucose concentrations should be within normal range, although the glucose tolerance curve may be somewhat flat if urinary glucose loss is considerable. The patient usually spills glucose in each urine specimen obtained, despite normal blood glucose levels.