Diabetes medications may be option for Fabry-related kidney damage
SGLT2 inhibitors found to reduce urine protein in Fabry patients in small study
SGLT2 inhibitors, medications approved for diabetes, could be used in Fabry disease to reduce albuminuria, which occurs when damaged kidneys let a large protein called albumin pass into the urine, according to a real-world study in adults with Fabry disease.
Because patients were followed for a short period of up to about 1.5 years, larger and longer studies are needed to confirm the effectiveness of SGLT2 inhibitors over time and to explore their effects on kidney health in Fabry disease.
“Given the nature of the study design and small case numbers, further long-term controlled studies are required to evaluate the long-term efficacy of this medication class,” researchers wrote.
The study, “Sodium-glucose cotransporter 2 inhibitors reduce albuminuria in patients with Fabry disease: a real-world case series,” was published in the International Medicine Journal.
Fabry disease is caused by genetic mutations leading to a deficiency of the enzyme alpha-galactosidase A. Without this enzyme, fatty molecules called glycosphingolipids build up to toxic levels in cells, causing damage to organs and resulting in symptoms.
SGLT2 inhibitors help kidneys remove sugar from body through urine
When glycosphingolipids damage the kidneys, patients may develop proteinuria, where too much protein leaks into the urine. SGLT2 inhibitors, which are used to treat diabetes by helping the kidneys to remove sugar from the body through urine, may also reduce proteinuria.
To explore this, researchers analyzed changes in the amount of albumin present in the urine of 11 adults with genetically confirmed Fabry disease, ages 48 to 59, who had been taking SGLT2 inhibitors for at least one month. All had evidence of albuminuria.
Eight patients (72%) also had signs of cardiomyopathy, or damage to the heart’s muscle, and two (18%) had diabetes. Eight (72%) had genetic mutations linked to classic Fabry disease, and three (27%) had non-classic genetic mutations.
Nearly two-thirds of patients (64%) were on enzyme replacement therapy, two (18%) were on chaperone therapy, one (9%) was on substrate reduction therapy, and one (9%) was not being treated with any Fabry disease-specific medications.
SGLT2 inhibitors — dapagliflozin, marketed as Farxiga or generics, or empagliflozin, available under the brand name Jardiance among others — were prescribed to reduce albuminuria, and used for an average of nine months. Ten patients reported no missed doses.
At the study’s start, median urine albumin-creatinine ratio (uACR), a measure of how well the kidneys are working, was 76 milligrams per millimole (mg/mmol). After treatment with SGLT2 inhibitors, uACR nearly halved, to a median 39 mg/mmol.
Patients with severe proteinuria showed most benefit from SGLT2 inhibitors
A reduction in albuminuria was observed in seven patients, with those experiencing severe proteinuria demonstrating the most benefit from SGLT2 inhibitors.
Side effects from SGLT2 inhibitors were mainly “transient.” Four patients had frequent urination, one felt lightheaded, and two developed urinary tract infections requiring antibiotics. One infection led to sepsis, which arises when the body’s immune response damages its own organs, causing the treatment to be stopped.
While these findings can’t be widely applied due to limitations in sample size, they suggest another possible treatment for kidney damage related to Fabry disease, where treatment choices are limited. “Larger-scale research is recommended to assess the efficacy and safety of [SGLT2 inhibitors],” the researchers wrote.
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