Marie-Noëlle Méaux1,2,3, Anne-Laure Sellier-Leclerc1, Cécile Acquaviva-Bourdain4, Jérôme Harambat2, Lise Allard2, Justine Bacchetta5,6,7. 1. Service de Néphrologie Rhumatologie Et Dermatologie Pédiatriques, Centre de Référence Des Maladies Rénales Rares Néphrogones Filières Maladies Rares ORKID et ERK-Net, Hospices Civils de Lyon, Lyon, Bron, France. 2. Service de Néphrologie Pédiatrique, Centre de Référence Des Maladies Rénales Rares Sorare, Filière Maladie Rare ORKID, CHU de Bordeaux, Bordeaux, France. 3. Service Biochimie Et Biologie Moléculaire, Maladies Héréditaires du Métabolisme, Hospices Civils de Lyon, Bron, France. 4. INSERM, UMR 1033, Faculté de Médecine Lyon Est, Université Claude Bernard Lyon1, Lyon, France. 5. Service de Néphrologie Rhumatologie Et Dermatologie Pédiatriques, Centre de Référence Des Maladies Rénales Rares Néphrogones Filières Maladies Rares ORKID et ERK-Net, Hospices Civils de Lyon, Lyon, Bron, France. justine.bacchetta@chu-lyon.fr. 6. Service Biochimie Et Biologie Moléculaire, Maladies Héréditaires du Métabolisme, Hospices Civils de Lyon, Bron, France. justine.bacchetta@chu-lyon.fr. 7. Faculté de Médecine Lyon Est, Université Claude Bernard, Lyon 1, Lyon, France. justine.bacchetta@chu-lyon.fr.
Abstract
BACKGROUND: Lumasiran, a sub-cutaneous RNA-interference therapy, has been recently approved for primary hyperoxaluria type 1 (PH1), with doses and intervals according to body weight. Little is known as to its use in infants; the aim of this study was to describe treatment outcome in 3 infants who received lumasiran therapy before 2 years of age. CASE-DIAGNOSIS/TREATMENT: Patient 1 was diagnosed antenatally and received lumasiran from day 9. According to the product information template (PIT), he received monthly lumasiran (3 times at 6 mg/kg, then 3 mg/kg), with hyperhydration and potassium citrate. Despite decreased plasma oxalate levels, persistent normal kidney function, and good tolerance, kidney ultrasound performed after 2 months found nephrocalcinosis, without normalization of urinary oxalate (UOx). The dose was increased back to 6 mg/kg, inducing a normalization in UOx. Nephrocalcinosis started to improve at month 10. Patient 2 was diagnosed at 2.5 months (acute kidney failure); nephrocalcinosis was present from diagnosis. She received monthly lumasiran (6 mg/kg), with progressive decrease in UOx and substantial improvement in kidney function but stable nephrocalcinosis after 9 injections. Patient 3 was diagnosed fortuitously (nephrocalcinosis) at 3.5 months and received lumasiran before genetic diagnosis, leading to decreased UOx and maintenance of normal kidney function. Nephrocalcinosis improved after 5 injections. CONCLUSIONS: This report presents the youngest children treated with lumasiran worldwide. Lumasiran seems effective without side effects in infants but does not completely prevent the onset of nephrocalcinosis in the most severe forms. Higher doses than those proposed in the PIT might be required because of hepatic immaturity.
BACKGROUND: Lumasiran, a sub-cutaneous RNA-interference therapy, has been recently approved for primary hyperoxaluria type 1 (PH1), with doses and intervals according to body weight. Little is known as to its use in infants; the aim of this study was to describe treatment outcome in 3 infants who received lumasiran therapy before 2 years of age. CASE-DIAGNOSIS/TREATMENT: Patient 1 was diagnosed antenatally and received lumasiran from day 9. According to the product information template (PIT), he received monthly lumasiran (3 times at 6 mg/kg, then 3 mg/kg), with hyperhydration and potassium citrate. Despite decreased plasma oxalate levels, persistent normal kidney function, and good tolerance, kidney ultrasound performed after 2 months found nephrocalcinosis, without normalization of urinary oxalate (UOx). The dose was increased back to 6 mg/kg, inducing a normalization in UOx. Nephrocalcinosis started to improve at month 10. Patient 2 was diagnosed at 2.5 months (acute kidney failure); nephrocalcinosis was present from diagnosis. She received monthly lumasiran (6 mg/kg), with progressive decrease in UOx and substantial improvement in kidney function but stable nephrocalcinosis after 9 injections. Patient 3 was diagnosed fortuitously (nephrocalcinosis) at 3.5 months and received lumasiran before genetic diagnosis, leading to decreased UOx and maintenance of normal kidney function. Nephrocalcinosis improved after 5 injections. CONCLUSIONS: This report presents the youngest children treated with lumasiran worldwide. Lumasiran seems effective without side effects in infants but does not completely prevent the onset of nephrocalcinosis in the most severe forms. Higher doses than those proposed in the PIT might be required because of hepatic immaturity.
Authors: Katharina Hopp; Andrea G Cogal; Eric J Bergstralh; Barbara M Seide; Julie B Olson; Alicia M Meek; John C Lieske; Dawn S Milliner; Peter C Harris Journal: J Am Soc Nephrol Date: 2015-02-02 Impact factor: 10.121
Authors: Sander F Garrelfs; Yaacov Frishberg; Sally A Hulton; Michael J Koren; William D O'Riordan; Pierre Cochat; Georges Deschênes; Hadas Shasha-Lavsky; Jeffrey M Saland; William G Van't Hoff; Daniel G Fuster; Daniella Magen; Shabbir H Moochhala; Gesa Schalk; Eva Simkova; Jaap W Groothoff; David J Sas; Kristin A Meliambro; Jiandong Lu; Marianne T Sweetser; Pushkal P Garg; Akshay K Vaishnaw; John M Gansner; Tracy L McGregor; John C Lieske Journal: N Engl J Med Date: 2021-04-01 Impact factor: 91.245
Authors: Lisa J Deesker; Sander F Garrelfs; Giorgia Mandrile; Michiel J S Oosterveld; Pierre Cochat; Georges Deschênes; Jérôme Harambat; Sally-Anne Hulton; Asheeta Gupta; Bernd Hoppe; Bodo B Beck; Laure Collard; Rezan Topaloglu; Larisa Prikhodina; Eduardo Salido; Thomas Neuhaus; Jaap W Groothoff; Justine Bacchetta Journal: Kidney Int Rep Date: 2022-04-20