C373 - Lumasiran Treatment and Isolated Kidney Transplantation in Primary Hyperoxaluria 1 and Late-Stage Chronic Kidney Disease

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Author Block: J. C. Lieske¹, E. Ben-Shalom², V. Belostotsky³, F. Knauf⁴, A. Sellier-Leclerc⁵, W. Du⁶, T. Kauf⁶, J. W. Groothoff⁷, ¹Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, ²Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel, ³Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, ⁴Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany, ⁵Hôpital Femme Mère Enfant en Centre d’Investigation Clinique INSERM, Hospices Civils de Lyon, Bron, France, ⁶Alnylam Pharmaceuticals, Cambridge, MA, ⁷Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, Netherlands
*Purpose: Ongoing hepatic oxalate production and systemic oxalate accumulation in patients (pts) with primary hyperoxaluria type 1 (PH1) and late-stage CKD have historically limited the feasibility of isolated kidney transplant (iKT). We reviewed data from the real-world observational BONAPH1DE study (BPH1; NCT04982393) and Phase 3 ILLUMINATE-C trial (ILLUM-C; NCT04152200) to assess if lumasiran could reduce oxalate burden and facilitate iKT in this high-risk population.
*Methods: BPH1 (N=174; all ages; any CKD stage) included 19 lumasiran ever-treated pts on dialysis and 11 not on dialysis with BL eGFR ≤45 mL/min/1.73m². ILLUM-C (N=21; all ages; late-stage CKD) included 15 pts on dialysis and 6 not on dialysis with BL eGFR ≤45; all initiated lumasiran. Post-iKT outcomes were evaluated in a subset of 7 BPH1 pts (lumasiran-treated at iKT; ≥1 year follow-up; ≥1 post-iKT POx and eGFR value) and 6 ILLUM-C pts.
*Results: In BPH1, pts not on dialysis had a mean (SD) BL eGFR of 18.9 (15.5) and BL POx of 110.5 (108.0) µmol/L; those on dialysis had a mean (SD) BL POx of 185.4 (348.6) µmol/L. In ILLUM-C, pts not on dialysis had a mean (SD) BL eGFR of 19.8 (9.6) and BL POx of 64.7 (41.3) µmol/L; those on dialysis had a mean (SD) BL POx of 108.4 (29.5) µmol/L (Figure). Generally, POx declined post-iKT among lumasiran-treated pts in BPH1 and ILLUM-C. In ILLUM-C, following lumasiran, POx was already reduced at the time of iKT (range: 19.2-93.2 µmol/L) and declined further post-iKT.
*Conclusions: In this group of pts with PH1 and late-stage CKD, lumasiran was associated with reduced POx pre- and post-iKT, with concordant findings across real-world and clinical trial settings. These results suggest that lumasiran can facilitate iKT in PH1 pts by reducing oxalate burden.