Recurrent 2,8‐Dihydroxyadenine Nephropathy: A Rare but Preventable Cause of Renal Allograft Failure

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8‐dihydroxyadenine (2,8‐DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8‐DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5–312) weeks following the transplant procedure. Patients had delayed graft function (n = 2), acute‐on‐chronic (n = 5) or acute (n = 1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8‐DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8‐DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n = 7), remained stable (n = 1) or worsened (n = 1). At last follow‐up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8‐DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss. The authors report on nine patients with recurrent 2,8‐dihydroxyadenine nephropathy following renal transplantation, pointing to adenine phosphoribosyltransferase deficiency as a rare but significant cause of renal allograft dysfunction.