Plasma Glycolate Levels Contribute to Drive the Decision of Isolated Kidney Transplantation in Dialyzed Patients with End-Stage Kidney Disease due to Primary Hyperoxaluria Type 1 Treated with Lumasiran: A Case Report.

Abstract

Introduction: Primary hyperoxaluria type 1 (PH1) is an inherited disease due to deficient activity of the liver enzyme AGT due to a mutation of the AGXT gene, leading to impairment in the glyoxylate metabolism with excessive oxalate urinary excretion (uOx) causing nephrolithiasis, renal failure, and systemic oxalosis. The historical treatment for renal failure was combined liver-kidney transplantation (CLKT) to restore normal function of AGT enzyme, but in mutations fully responsive to pyridoxine, an isolated kidney transplant (IKT) is feasible. Recently, RNA-interference (RNAi) agents such as lumasiran that reduce the oxalate synthesis in PH1 patients open new therapeutic challenges such as IKT irrespective of the type of AGXT gene mutation. Nevertheless, to decide for IKT instead of CLKT, clinicians must be aware of lumasiran efficacy. At present, the biomarker used to evaluate the lumasiran efficacy is the plasma oxalate (pOx). However, in dialyzed patients, pOx might be influenced by the release of oxalate from the deposits to the blood.

Case presentation: We report the case of a PH1 36-year-old male patient who underwent IKT combined with lumasiran. Two years after transplantation, graft function is good without lithiasis or nephrocalcinosis. 24-h uOx varies from 0.55 to 1.2 mmol/day and pOx remains stable at 12 μmol/L. Allograft biopsies at 1, 6, 12, and 22 months show negligible oxalate crystals deposits.

Conclusion: The novelty of our case lies in the methods we adopted to evaluate the lumasiran efficacy during dialysis prior listing for IKT. Specifically, we decided to list the patient for IKT according to the high plasma levels of glycolate reached after lumasiran treatment together with the significant reduction of the pOx.