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Kidney Week

Abstract: FR-PO589

Heart Failure Recovery After Lumasiran and Isolated Kidney Transplantation in Primary Hyperoxaluria Type 1

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Hawkins-van der Cingel, Gerlineke M C, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Choi, Mira, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Kahl, Andreas, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Schoenrath, Felix, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Rehse, Gregor, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Eckardt, Kai-Uwe, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Knauf, Felix, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Halleck, Fabian, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
Introduction

Primary hyperoxaluria type 1 (PH1) is characterized by oxalate stones leading to kidney failure. In advanced PH1, systemic oxalate deposition may lead to heart failure. Lumasiran, a small interfering RNA, reduces oxalate load and may improve organ dysfunction in systemic oxalosis.

Case Description

A kidney biopsy revealed diffuse interstitial nephritis with massive oxalate deposition. Genetic testing confirmed two compound heterozygous Alanine-Glyoxylate Aminotransferase (AGXT) gene mutations. Our patient had peritoneal dialysis (PD) for 6 months. In addition, he suffered from severe heart failure (NYHAIII) with a left ventricular ejection fraction (LVEF) of 25%, marked left ventricular hypertrophy and a NTproBNP of >50,000pg/mL. A cardiac biopsy revealed severe oxalate deposition. Hemodialysis (HD) therapy was commenced to optimize volume overload and lower plasma oxalate (POx) levels. The initial POx level of 141.3µmol/L decreased to less than half after combined PD and HD. After starting lumasiran and high dose pyridoxine, POx levels further decreased to 29.2µmol/L. Subsequently, cardiac output improved to an LVEF of 35-40%. He received a living kidney donation from his father using standard immunosuppression and intensive hydration post transplantation. Daily oral pyridoxine and 3 monthly subcutaneous lumasiran was continued. At 3 months follow up, allograft function stabilized at a creatinine of 2.0 mg/dL. An allograft biopsy showed no oxalate deposition. His cardiac function improved further (NYHAI, LVEF 55%, NTproBNP of 449pg/mL) with a recent POx level of 11µmol/L.

Discussion

To our knowledge, this is the first case demonstrating complete remission of heart failure in a patient with PH1 following lumasiran therapy and isolated kidney transplantation. This underscores the utility of lumasiran and the conclusion that cardiac dysfunction related to PH1 is potentially reversible.