Tom Nijenhuis and Jeroen de Baaij, theme Renal disorders, received a Dutch Kidney Foundation Innovation grant together with colleagues from ErasmusMC and AmsterdamUMC for their project “A sweet deal: repurposing SGLT2i for renal hypomagnesemia”.
Renal hypomagnesemia occurs in rare kidney disorders like ADTKD-HNF1b and Gitelman syndrome, but is also a side-effect of several widely-prescribed drugs. Hypomagnesemia can result in chronic fatigue, muscle weakness, neurological symptoms and neurocognitive deficits. The only treatment option is magnesium supplementation, which has dose-limiting gastrointestinal side-effects most often leading to insufficient correction of serum magnesium and persistence of symptoms.
SGLT2 inhibitors, used to treat diabetes, have pleiotropic effects which also appears to include a renal magnesium-sparing potential. Case reports suggests that this beneficial effect may be considerable in particular in renal hypomagnesemia. On the one hand, the researchers will perform N-of-1 trials in patients with a rare renal hypomagnesemia to study the effect of SGLT2 inhibition on serum magnesium and symptoms. On the other hand, they will study the molecular mechanism of the magnesium-sparing action of SGLT2 inhibition in animal studies.
Jeroen de Baaij is assistant professor at the department of Physiology studying the genetic and molecular origins of electrolyte disorders, including magnesium wasting. Tom Nijenhuis is internist-nephrologist at the department of Nephrology focusing on the pathogenesis and treatment of rare kidney disorders, including magnesium-wasting tubulopathies.
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