SUN-328 ADENINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY: A POTENTIALLY REVERSIBLE CAUSE OF CHRONIC KIDNEY DISEASE IN THE PRE AND POST TRANSPLANT SETTING

Abstract

Adenine phosphoribosyltransferase (APRT) deficiency is a rare, autosomal recessive disorder which results in increased production of 2,8-dihydroxyadenine (DHA) viathe purine salvage pathway. Excess DHA is excreted in the urine, where it forms highly insoluble crystals and manifests as either urolithiasis or crystalline nephropathy. The onset and presentation of disease is variable and may present as chronic kidney disease of unknown aetiology; renal calculi; misdiagnosed oxalate nephropathy; graft dysfunction following renal transplantation; or through family screening. DHA crystals have distinct appearance on renal biopsy and urine microscopy, but is easily misdiagnosed or unrecognized due to low clinical suspicion. Diagnosis is of paramount importance; as chronic renal injury can be potentially can be minimized with xanthine oxidase inhibitors (allopurinol or feboxustat). We present cases of 3 cases of APRT deficiency (2 patients were post cadevaric renal transplantation). Patient characteristics pre and post transplantation will be presented in a table, including information on renal function, oxipurinol levels and urine microscopy. Indication and protocol transplant renal biopsies were processed as standard protocol and evaluated for rejection (according to Banff criteria) and crystal nephropathy (percentage of biopsy affected and distribution in luminal, epithelial and interstitial compartments). Both transplant patients had early recurrence of crystalline nephropathy (figure 1) and necessitated rapid escalation of xanthine oxidase inhibitors to levels exceeding recommendations for renal impairment. Both patients were also treated for borderline rejection and this highlights the difficulties in delineating rejection from crystal-associated inflammation. One patient developed Banff 2A rejection but both patients suffered infective complications of excess immunosuppression. Review of all available transplant biopsies revealed interesting kinetics of crystal formation and deposition in the kidney. Early in the disease, with maximal excretion of DHA metabolites in urine leads to crystal precipitation, luminal aggregate with tubular obstruction and injury. These crystals then are seen in the epithelial layer (either by encapsulation or endocytosis). Later in the disease, there is associated tubular rupture and interstitial deposition with associated interstitial fibrosis and tubular atrophy (figure 2). The amount of luminal crystals reduce over time with increasing dose of allopurinol and/or feboxustat. Lack of awareness and clinical suspicion appear to be a major barrier to timely diagnosis, although multiple management challenges post diagnosis remains. The current target levels and biomarkers of adequacy of therapy with allopurinol and/or feboxustat remains to be determined.