Knocking out the Sweetest Urine
- Genetic Diseases: Tubulopathies
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
- Fuentes, Stepfany, Maine Medical Center, Portland, Maine, United States
- Segal, Alan, Maine Medical Center, Portland, Maine, United States
SGLT2 inhibitors—which act on a Na-glucose co-transporter in the apical membrane along the proximal tubule—lead to natriuresis and glycosuria, and have been shown to have an astonishing salutary effect on slowing CKD, perhaps in part by stimulating tubuloglomerular feedback. Here, we present siblings with a naturally occurring loss-of-function mutation of the SGLT2 co-transporter.
A 44-year-old male presented to the clinic for glucosuria first discovered at age 10. He reported concurrent polyuria and polydipsia since childhood. He denied history of UTI, dysuria, urinary retention, change in appetite, or change in vision. His biological sister was found to have glucosuria as well. Both have enjoyed perfect health with normal blood pressure, electrolytes, and kidney function; both have normoglycemia and neither have diabetes. A 24-hour urine demonstrated 29 g glucose in 3.1 L (935.5 mg/dL). Genetic testing revealed a mutation in SLC5A2, the gene encoding the SGLT2 co-transporter.
In these siblings, an SLC5A2 loss-of-function variant c. 1152_1163del (p.Val385-Ala288del) is the cause of their familial renal glucosuria. While the SGLT2 inhibitor class of medication is growing in popularity for its known benefits at reducing CV disease and progression of CKD, few studies have evaluated the effect of the gene mutation induced glucosuria. One study of 13 family members in Finland with a SLC5A2 genetic mutation was followed over 30 years. While they were at increased risk of urinary tract infections and postprandial hypoglycemia, there has been no effect on glucose tolerance and they maintain normal kidney function. We conclude that, as has been the case with other genetic abnormalities of transporters along the nephron, individuals and families with SLC5A2 mutations should be studied in an effort to elucidate the potential mechanisms that underlie the beneficial effects of SGLT2 inhibitors in patients with kidney disease.