Multicenter Long-Term Real World Data on Treatment With Lumasiran in Patients With Primary Hyperoxaluria Type 1
Cristina Martín-Higueras, Lodovica Borghese, Armando Torres, Fátima Fraga-Bilbao, Raquel Santana‐Estupiñán, Constantinos J. Stefanidis, Kálmán Tory, Adam Walli, Leire Gondra, Caroline Kempf, Michaela Geßner, Sandra Habbig, Lisa Eifler, Claus Peter Schmitt, Benjamin Rüdel, Malte P. Bartram, Bodo B. Beck, Bernd Höppe
Abstract
IntroductionThe RNA interference medication lumasiran reduces hepatic oxalate production in primary hyperoxaluria type 1 (PH1). Data outside clinical trials are scarce.MethodsWe report on retrospectively and observationally obtained data in 33 PH1 patients (20 with preserved kidney function, 13 on dialysis) treated with lumasiran for a median of 18 months.ResultsPreserved kidney function: mean urine oxalate (Uox) decreased from 1.88 (baseline) to 0.73 mmol/1.73m2/24h after 3, to 0.72 at 12 and to 0.65 at 18 months, but differed according to vitamin B6 medication. Highest response was at month 4 (0.55, -70.8%). Plasma oxalate (Pox) remained stable over time. Glomerular filtration rate significantly increased by 10.5 % at month 18. Nephrolithiasis continued active in 6, nephrocalcinosis ameliorated or progressed in one patient each. At last follow up Uox remained above 1.5 upper limit of normal (> 0.75 mmol/1.73m2/24h) in 6 patients. Urine and plasma glycolate (Pglyc) significantly increased in all, urine citrate decreased and alkali medication needed adaptation. Dialysis: mean Pox and Pglyc significantly decreased, and increased, respectively after monthly dosing (Pox: 78 to 37.2, Pglyc 216.4 to 337.4 μmol/l). At quarterly dosing neither Pox nor Pglyc were significantly different to baseline. An acid state was buffered by an increased dialysis regimen. Systemic oxalosis remained unchanged.ConclusionLumasiran treatment is safe and efficient. Dosage (interval) adjustment necessities need clarification. In dialysis, lack of Pox reduction may relate to dissolving systemic oxalate deposits. Pglyc increment may be a considerable acid load requiring careful consideration, which definitively needs further investigation.