Kidney Transplant Outcomes in Patients With Adenine Phosphoribosyltransferase Deficiency

Abstract

Background: Adenine phosphoribosyltransferase (APRT) deficiency is a rare, hereditary cause of kidney stones and chronic kidney disease (CKD) which is characterized by 2,8-dihydroxyadenine renal parenchymal crystal deposition. The aim of this study was to examine outcomes of kidney transplantation in APRT deficiency patients.

Methods: Included were 13 patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, 2 from Westmead Hospital in Sydney, Australia, and 2 from Necker Hospital in Paris, France. The CKD-EPI and CKiD equations were used to calculate glomerular filtration rate estimates. Allograft survival was analyzed employing the Kaplan-Meier method. The Wilcoxon-Mann-Whitney test was used to compare alllograft outcomes according to xanthine oxidoreductase (XOR) inhibitor treatment status at transplantation.

Results: Seventeen patients (9 females) received 22 kidney transplants. Age at first transplantation was 47.2 (14.9-67.0) years. Ten patients received XOR inhibitor therapy pretransplant (11 allografts), while 8 patients did not receive such treatment before transplantation (11 allografts). Two-year allograft survival was 91% and 55% in the 2 groups, respectively (P = 0.16). The median (range) estimated glomerular filtration rate at 2 years posttransplant was 61.3 (24.0-90.0) mL/min/1.73 m when XOR inhibitor therapy was initiated before transplantation, and 16.2 (10.0-39.0) mL/min/1.73 m (P = 0.009) when such treatment was not administered pretransplant.

Conclusions: Kidney allograft outcomes are good in APRT deficiency patients beginning XOR inhibitor therapy pretransplant. Delay in such treatment is a major cause of premature graft loss in these patients. Increased awareness among clinicians is imperative, promoting early diagnosis of APRT deficiency and pharmacotherapy initiation before kidney transplantation.

Figure 1.

Recurrent DHA nephropathy in an allograft from 1 of the patients (No 12; Table 2). A. On a hematoxylin and eosin stained section, numerous brown crystals (arrows) are seen within tubular lumens and within the tubular epithelial cytoplasm (left panel). Upon examination under polarized light, these crystals are strongly birefringent (right panel). B. On high magnification (600x) of the hematoxylin and eosin stained section, small brown crystals (arrows) are often seen within the tubular epithelial cytoplasm.

Figure 1.

Recurrent DHA nephropathy in an allograft from 1 of the patients (No 12; Table 2). A. On a hematoxylin and eosin stained section, numerous brown crystals (arrows) are seen within tubular lumens and within the tubular epithelial cytoplasm (left panel). Upon examination under polarized light, these crystals are strongly birefringent (right panel). B. On high magnification (600x) of the hematoxylin and eosin stained section, small brown crystals (arrows) are often seen within the tubular epithelial cytoplasm.

Figure 2.

Kaplan-Meier curve of death-censored kidney allograft survival from the time of kidney transplantation in patients who received treatment with an XOR inhibitor pretransplant (solid line) and those who did not (broken line).