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Long-term renal outcomes of APRT deficiency presenting in childhood

  • Hrafnhildur Linnet Runolfsdottir
  • Runolfur PalssonEmail author
  • Inger MSch Agustsdottir
  • Olafur S Indridason
  • Vidar O EdvardssonEmail author
Original Article

Abstract

Background

Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary purine metabolism disorder that causes kidney stones and chronic kidney disease (CKD). The purpose of this study was to examine the course of APRT deficiency in patients who presented in childhood.

Methods

The disease course of 21 (35%) patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, who presented with manifestations of APRT deficiency and/or were diagnosed with the disorder before the age of 18 years, was studied. The effect of pharmacotherapy on renal manifestations and outcomes was thoroughly assessed.

Results

Fourteen children were placed on allopurinol, 100 (25–200) mg/day, at the age of 2.6 (0.6–16.5) years. Six of these patients had experienced kidney stone events and three had developed acute kidney injury (AKI) prior to allopurinol treatment. During 18.9 (1.7–31.5) years of pharmacotherapy, stones occurred in two patients and AKI in three. Six adult patients started allopurinol treatment, 200 (100–300) mg/day, at age 29.8 (20.5–42.4) years. Five of these patients had experienced 28 stone episodes and AKI had occurred in two. Stone recurrence occurred in four patients and AKI in two during 11.2 (4.2–19.6) years of allopurinol therapy. Lack of adherence and insufficient dosing contributed to stone recurrence and AKI during pharmacotherapy. At latest follow-up, estimated glomerular filtration rate (eGFR) was 114 (70–163) and 62 (10–103) mL/min/1.73 m2 in those who initiated treatment as children and adults, respectively. All three patients with CKD stages 3–5 at the last follow-up were adults when pharmacotherapy was initiated.

Conclusion

Timely diagnosis and treatment of APRT deficiency decreases renal complications and preserves kidney function.

Keywords

Kidney stones Nephrolithiasis Chronic kidney disease Kidney failure Crystal nephropathy Kidney transplantation Allopurinol Children 

Notes

Acknowledgements

Part of this work was presented in an abstract form at the American Society of Nephrology Kidney Week, November 3–8, 2015, San Diego, CA. The authors want to sincerely thank the following physicians for their invaluable assistance in clinical data and biosample collection: Dawn Milliner (Mayo Clinic, Rochester, MN, USA), John Lieske (Mayo Clinic, Rochester, MN, USA), David Goldfarb (New York University, New York, NY, USA), Philipp Eller (Medical University of Graz, Graz, Austria), Hans-Jacob Bangstad (Oslo University Hospital, Oslo, Norway), Amrik Sahota (Rutgers University, Piscataway, NJ, USA), and Lynette Fairbanks (Guy’s and St. Thomas’ Hospital NHS Foundation Trust, London, UK).

Support

This study was supported by the Rare Kidney Stone Consortium (2U54DK083908), a part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR). The Rare Kidney Stone Consortium is funded through collaboration between NCATS and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Compliance with ethical standards

The study was approved by the National Bioethics Committee of Iceland (NBC 09-072) and the Icelandic Data Protection Authority. All living patients or their legal guardians gave a written informed consent for participation in the study. The work described has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Edvardsson V, Palsson R, Olafsson I, Hjaltadottir G, Laxdal T (2001) Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. Am J Kidney Dis 38:473–480CrossRefGoogle Scholar
  2. 2.
    Bollee G, Dollinger C, Boutaud L, Guillemot D, Bensman A, Harambat J, Deteix P, Daudon M, Knebelmann B, Ceballos-Picot I (2010) Phenotype and genotype characterization of adenine phosphoribosyltransferase deficiency. J Am Soc Nephrol 21:679–688CrossRefGoogle Scholar
  3. 3.
    Runolfsdottir HL, Palsson R, Agustsdottir IM, Indridason OS, Edvardsson VO (2016) Kidney disease in adenine phosphoribosyltransferase deficiency. Am J Kidney Dis 67:431–438CrossRefGoogle Scholar
  4. 4.
    Harambat J, Bollee G, Daudon M, Ceballos-Picot I, Bensman A (2012) Adenine phosphoribosyltransferase deficiency in children. Pediatr Nephrol 27:571–579CrossRefGoogle Scholar
  5. 5.
    Greenwood MC, Dillon MJ, Simmonds HA, Barratt TM, Pincott JR, Metreweli C (1982) Renal failure due to 2,8-dihydroxyadenine urolithiasis. Eur J Pediatr 138:346–349CrossRefGoogle Scholar
  6. 6.
    Debray H, Cartier P, Temstet A, Cendron J (1976) Child’s urinary lithiasis revealing a complete deficit in adenine phosphoribosyl transferase. Pediatr Res 10:762–766PubMedGoogle Scholar
  7. 7.
    Chiba P, Zwiauer K, Muller MM (1988) Characterization of an adenine phosphoribosyltransferase deficiency. Clin Chim Acta 172:141–147CrossRefGoogle Scholar
  8. 8.
    Edvardsson VO, Palsson R, Sahota A (2012). Adenine phosphoribosyltransferase deficiency. August 30, 2012 [updated June 18, 2015]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2015. https://www.ncbi.nlm.nih.gov/books/NBK100238/ Accessed June 8, 2018.
  9. 9.
    Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefGoogle Scholar
  10. 10.
    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefGoogle Scholar
  11. 11.
    Skali H, Uno H, Levey AS, Inker LA, Pfeffer MA, Solomon SD (2011) Prognostic assessment of estimated glomerular filtration rate by the new Chronic Kidney Disease Epidemiology Collaboration equation in comparison with the Modification of Diet in Renal Disease Study equation. Am Heart J 162:548–554CrossRefGoogle Scholar
  12. 12.
    Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150Google Scholar
  13. 13.
    Kidney Disease: Improving Global Outcomes (KDIGO) AKI Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. AKI definition. Kidney Int Suppl 2:19–36CrossRefGoogle Scholar
  14. 14.
    Zaidan M, Palsson R, Merieau E, Cornec-Le Gall E, Garstka A, Maggiore U, Deteix P, Battista M, Gagne ER, Ceballos-Picot I, Duong Van Huyen JP, Legendre C, Daudon M, Edvardsson VO, Knebelmann B (2014) Recurrent 2,8-dihydroxyadenine nephropathy: a rare but preventable cause of renal allograft failure. Am J Transplant 14:2623–2632CrossRefGoogle Scholar
  15. 15.
    Edvardsson VO, Runolfsdottir HL, Thorsteinsdottir UA, Agustsdottir IMSch, Oddsdottir GS, Eiriksson F, Goldfarb DS, Thorsteinsdottir M, Palsson R (2018) Comparison of the effect of allopurinol and febuxostat on urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency (APRTd): a clinical trial. Eur J Intern Med 48:75–79CrossRefGoogle Scholar
  16. 16.
    Thorsteinsdottir M, Thorsteinsdottir UA, Eiriksson FF, Runolfsdottir HL, Agustsdottir IM, Oddsdottir S, Sigurdsson BB, Hardarson HK, Kamble NR, Sigurdsson ST, Edvardsson VO, Palsson R (2016) Quantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency. J Chromatogr B Analyt Technol Biomed Life Sci 1036-1037:170–177CrossRefGoogle Scholar

Copyright information

© IPNA 2018

Authors and Affiliations

  1. 1.Faculty of Medicine, School of Health SciencesUniversity of IcelandReykjavikIceland
  2. 2.Internal Medicine ServicesLandspitali–The National University Hospital of IcelandReykjavikIceland
  3. 3.Children’s Medical Center, Landspitali–The National University Hospital of IcelandReykjavikIceland

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