Chronic Allograft Injury by Recurrent Crystalline Nephropathy of Adenine Phosphoribosyl Transferase Deficiency, Even after Early Initiation of Xanthine Oxidase Inhibitor.

Abstract

Introduction: Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic disorder of purine metabolism that results in excessive renal excretion of poorly soluble 2,8-dihydroxyadenine (DHA), leading to urolithiasis, crystalline nephropathy, and renal failure. Recurrence after renal transplantation usually occurs in the early posttransplantation period and is sometimes the initial indication for the disease. Allograft survival is poor without adequate treatment with xanthine oxidase (XOR) inhibitors to reduce DHA levels.

Case presentation: A 49-year-old Japanese man with a history of recurrent renal stones presented with mild renal dysfunction 3 months after renal transplantation. Allograft biopsy revealed numerous brown crystals within the tubules and active interstitial inflammation. Febuxostat, a high-dose XOR inhibitor, was immediately prescribed. APRT deficiency was confirmed through urine metabolome analysis. The patient's renal function improved, and the febuxostat dose was subsequently reduced. One-year allograft biopsy demonstrated markedly reduced inflammation and crystals; however, an expanded scarred area with focal active inflammation and a few small crystals were observed.

Conclusion: XOR inhibitors effectively reduce the crystals of recurrent APRT deficiency; however, they cannot prevent chronic injury. Diagnosing recurrent crystalline nephropathy and initiating XOR inhibitors as early as possible is essential for improving allograft survival.