The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study
Status:
Recruiting
Trial end date:
2022-06-01
Target enrollment:
Participant gender:
Summary
Cystinuria is an inherited autosomal recessive disorder of the kidney that is the result of
an inability to reabsorb cystine from the urine. Supersaturation of cystine in the urine
produces crystals that precipitate and form stones in the kidney, which can be a cause of
obstruction, infection, and chronic kidney disease. Cystine stones constitute a major health
challenge for affected individuals with cystinuria because of the frequent recurrence of
painful symptoms and the current absence of effective, patient-accepting treatment.
A mainstay of therapy is breaking or preventing the cystine bond on the molecular level such
that cystine (which is formed from the joining of two cysteine amino acids and their
corresponding sulfur atoms) cannot precipitate in the urine. It is hypothesized that a
glucose molecule may be able to do this if introduced into the urine. SGLT-2 inhibitors are a
class of drug that are FDA approved to treat diabetes mellitus (DM) and heart failure by
inhibiting an enzyme in the kidney that allows for reabsorption of glucose from the urine.
This effectively increases the concentration of glucose in the urine. Our hypothesis suggests
that administration of this drug to patients with cystine will introduce sufficient glucose
into the urine to prevent the formation of cystine stones. To date, there has been no
published data on the effectiveness of this therapy for this indication, although the dosage
and administration would be identical to that already approved by the FDA for the treatment
of DM and heart failure.