The
primary hyperoxalurias are three rare inborn errors of the
glyoxylate metabolism in the liver, which lead to massively increased endogenous
oxalate production, thus elevating urinary
oxalate excretion and, based on that, recurrent
urolithiasis and/or progressive
nephrocalcinosis. Frequently, especially in type 1
primary hyperoxaluria, early
end-stage renal failure occurs. Treatment possibilities are scare, namely,
hyperhydration and alkaline
citrate medication. In type 1
primary hyperoxaluria,
vitamin B6, though, is helpful in patients with specific missense or mistargeting mutations. In those
vitamin B6 responsive, urinary
oxalate excretion and concomitantly urinary
glycolate is significantly decreased, or even normalized. In patients non-responsive to
vitamin B6, RNA interference medication is now available. Lumasiran® is already available on prescription and targets the
messenger RNA of
glycolate oxidase, thus blocking the conversion of
glycolate into
glyoxylate, hence decreasing
oxalate, but increasing
glycolate production.
Nedosiran blocks liver-specific
lactate dehydrogenase A and thus the final step of
oxalate production. Similar to
vitamin B6 treatment, where both RNA interference urinary
oxalate excretion can be (near) normalized and plasma
oxalate decreases, however, urinary and plasma
glycolate increases with
lumasiran treatment. Future treatment possibilities are on the horizon, for example, substrate reduction
therapy with small molecules or gene editing, induced pluripotent stem cell-derived autologous hepatocyte-like
cell transplantation, or gene therapy with newly developed vector technologies. This review provides an overview of current and especially new and future treatment options.