Kidney Disease in Adenine Phosphoribosyltransferase Deficiency

Abstract

Background: Adenine phosphoribosyltransferase (APRT) deficiency is a purine metabolism disorder causing kidney stones and chronic kidney disease (CKD). The course of nephrolithiasis and CKD has not been well characterized. The objective of this study was to examine long-term kidney outcomes in patients with APRT deficiency.

Study design: An observational cohort study.

Setting & participants: All patients enrolled in the APRT Deficiency Registry of the Rare Kidney Stone Consortium.

Outcomes: Kidney stones, acute kidney injury (AKI), stage of CKD, end-stage renal disease, estimated glomerular filtration rate (eGFR), and changes in eGFR.

Measurements: Serum creatinine and eGFR calculated using creatinine-based equations.

Results: Of 53 patients, 30 (57%) were females and median age at diagnosis was 37.0 (range, 0.6-67.9) years. Median duration of follow-up was 10.3 (range, 0.0-31.5) years. At diagnosis, kidney stones had developed in 29 (55%) patients and 20 (38%) had CKD stages 3 to 5, including 11 (21%) patients with stage 5. At latest follow-up, 33 (62%) patients had experienced kidney stones; 18 (34%), AKI; and 22 (42%), CKD stages 3 to 5. Of 14 (26%) patients with stage 5 CKD, 12 had initiated renal replacement therapy. Kidney stones recurred in 18 of 33 (55%) patients. The median eGFR slope was -0.38 (range, -21.99 to 1.42) mL/min/1.73m(2) per year in patients receiving treatment with an xanthine dehydrogenase inhibitor and -5.74 (range, -75.8 to -0.10) mL/min/1.73m(2) per year in those not treated prior to the development of stage 5 CKD (P=0.001).

Limitations: Use of observational registry data.

Conclusions: Progressive CKD and AKI episodes are major features of APRT deficiency, whereas nephrolithiasis is the most common presentation. Advanced CKD without a history of kidney stones is more prevalent than previously reported. Our data suggest that timely therapy may retard CKD progression.

Keywords: End-stage renal disease; acute kidney injury (AKI); adenine phosphoribosyltransferase (APRT) deficiency; chronic kidney disease (CKD); crystal nephropathy; disease progression; estimated glomerular filtration rate (eGFR); kidney failure; kidney stone; nephrolithiasis; purine metabolism disorder; renal function; renal replacement therapy (RRT).

Figure 1

Urinary 2,8-dihydroxyadenine crystals. (A) The characeristic medium-sized crystals are brown with a dark outline and central spicules. (Original magnification, ×400). (B) The same field viewed with polarized light microscopy shows that the small- and medium-sized crystals appear yellow in color and produce a central Maltese cross pattern. (Original magnification, ×400)

Figure 2

Age distribution (A) at the occurrence of first kidney stone event and (B) at the detection of CKD stage 5 in patients with adenine phosphoribosyltransferase deficiency.

Figure 2

Age distribution (A) at the occurrence of first kidney stone event and (B) at the detection of CKD stage 5 in patients with adenine phosphoribosyltransferase deficiency.

Figure 3

Chronic kidney disease stages 3–5 in patients with adenine phosphoribosyltransferase deficiency from Iceland and other countries at the time of diagnosis. Abbreviations: CKD, chronic kidney disease.

Figure 4

Kidney stones, chronic kidney disease stages 3–5 and initiation of renal replacement therapy in patients with adenine phosphoribosyltransferase deficiency who received xanthine dehydrogenase inhibitor treatment and those who did not. Abbreviations: KS, kidney stones; CKD, chronic kidney disease; RRT, renal replacement therapy.

Figure 5

Boxplot of estimated glomerular filtration rate in different age groups of patients with adenine phosphoribosyltransferase deficiency. Patients contributed data to every age group for which they had serum creatinine value available and for each individual the mean of all eGFR values in any given age group was used. Patients receiving renal replacement therapy were assigned an eGFR of 10 mL/min/1.73m². Abbreviations: eGFR, estimated glomerular filtration rate.