#4487 AN UNEXPECTED CASE OF 2,8-DIHYDROXYADENINE NEPHROPATHY AFTER KIDNEY TRANSPLANTATION RELATED TO NEW VARIANTS OF ADENINE PHOSPHORIBOSILTRANSFERASE GENE
Authors: Brigante Fabiana , Tortora Giada , Mazzucchelli Roberta , Moretti Maria Ilaria , Valente Mauro , Viola Valentina , Moretti Marco , Balestra Emilio , Taruscia Domenica , Ranghino Andrea 
Published: June 2023

Background and Aims

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of the purine metabolism which results in the conversion of adenine into 2,8 dihydroxyadenine (DHA) due to the activity of the xanthine oxidoreductase (XOR). Patients affected by APRT deficiency if not treated with inhibitors of XOR may develop 2,8-DHA nephropathy that might progress to end-stage kidney disease (ESKD) with the need of kidney transplant. The high rate of misdiagnosis of 2,8-DHA nephropathy in native kidneys could lead to the failure of kidney graft in transplanted patients affected by APRT deficiency.

Method

Here, we report the case of a female, 63-years old patient with ESKD of unknown cause on regular hemodialysis treatment from 2018 after a period of three years on peritoneal dialysis, who underwent kidney transplantation in our Center in 2022. Her medical history showed a metabolic syndrome. She did not experience episodes of renal colic whereas family history reported a brother affected by frequent renal colic of unknown cause. In March 2022, she underwent kidney transplantation from a deceased death brain donor. Induction therapy includes basiliximab, tacrolimus, mycophenolic acid and steroids. Due to the persistence of delay graft function, ten days after kidney transplantation an allograft biopsy has been performed. The histological examination revealed tubular damage surrounded by inflammation cells and intratubular crystals in the renal cortex. The crystals were reddish brown tinged in hematoxylin and eosin stain and were birefringent under polarized light Fig. 1 A, B, so they were strongly related to the hypothesis of DHA crystals. Consistently, the urinalysis showed yellow-brown crystals of DHA. Thus, a genetic analysis of APRT gene has been performed showing two novel heterozygous variants c.388_397p.(Leu130ValfsTer4) and exon 3 deletion, expected pathogenic. The patient was treated with bolus of methylprednisolone (4mg/kg alternate to 50 mg) and a therapy with febuxostat 80 mg/die was started to reduce the amount of plasma DHA. In addition, based on our previous experience of recurrence DHA nephropathy after transplantation, we treated the patient with six consecutive hemodiafiltration (HDF) sessions without ultrafiltration, to promptly remove the serum DHA avoiding their precipitation in the graft while waiting for the lowering effect of febuxostat. At discharge the patient showed an increase of the urine output not associated with a complete recovery of kidney function (sCr 3.88 mg/dl, uric acid 1.6 mg/dl), so two other hemodialysis treatments were performed in the next two weeks.

Results

At present, almost one year after kidney transplant, the patient is doing well and the graft function is stable with a sCr of 1.6 mg/dl without significant presence of DHA crystals in the urine.

Conclusion

In conclusion, we find out an unexpected recurrence of 2,8-DHA nephropathy due to novel expected pathogenetic variants of APRT gene in patient without medical history of kidney stones successfully treated with steroid, febuxostat and hemodiafiltration.