ESPN 53rd Annual Meeting

ESPN 2021


 
RNA interference therapy may allow withdrawal of nocturnal hyperhydration in children with primary hyperoxaluria
NATHALIE BIEBUYCK 1 OLIVIA BOYER 1

1- NéPHROLOGIE PéDIATRIQUE, MARHEA, INSTITUT IMAGINE, UNIVERSITé DE PARIS, HôPITAL NECKER - ENFANTS MALADES, APHP, PARIS, FRANCE
 
Abstract:

Primary hyperoxaluria type 1 (PH1) is a rare inherited disease associated with  excessive liver oxalate production and consequent systemic accumulation and severe organ involvement. Treatment consists in nychthemeral hyperhydration, crystallization inhibitors, pyridoxine and eventually kidney-liver transplantation. This treatment has a high negative impact on quality-of-life, even before transplantation, especially nocturnal hyperhydration on a G-tube. Recently, ARN interference therapy (Lumasiran) was shown to significantly decrease oxaluria in PH1. There are however no recommendations about the discontinuation of the burdensome supportive measures. We present here 2 patients with PH1 who stopped the nocturnal hyperhydration with promising outcomes.

Patient 1, a 16 yo girl, and Patient 2, a 14 yo boy, were diagnosed with PH1 at the age of 6 months with bilateral nephrocalcinosis, elevated urinary oxalate/creatinine ratio, whewellite urinary crystals and AGXT variants. They were prescribed hyperhydration via a G-tube, crystallization inhibitors and pyridoxine. This allowed disappearance of crystals in the urine, reduction of urinary oxalate/creatinine ratio and regression of nephrocalcinosis. Patient 1 had adherence difficulties and psychological distress and decided to stop nocturnal hyperhydration at the age of 12 and nephrocalcinosis and bilateral lithiasis reappeared at the age of 14. Lumasiran was begun at the age of 15 years and 13 years, respectively. We rapidly observed normal oxaluria/creatininuria and calciuria/creatininuria, negative crystalluria and regression of lithiasis (patient 1) or persistently normal kidney ultrasound (patient 2). We decided to withdraw nocturnal hydration after 6 months in Patient 2 due to difficult-to-tolerate enuresis. 3 months after withdrawal, oxaluria, calciuria and crystalluria remain normal. The control kidney ultrasound is pending.

Lumasiran seems very efficient to normalize oxaluria even in patients with no nocturnal hyperhydration because of non-adherence or in order to improve the quality-of-life. Additional data and longer follow-up are needed to guide updated treatment recommendations .